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Patient-Driven Care Plus Telemonitoring Yields Promising Results for Spondyloarthritis
VIENNA — People with spondyloarthritis (SpA) who have low or stable disease activity can effectively and safely be managed using a model of patient-initiated care with or without remote monitoring, suggested the results of two separate trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.
In the 18-month, single-center ReMonit study that included 243 people with axial SpA (axSpA), patient-initiated care was found to be noninferior for keeping them in a low-disease activity state, compared with both usual hospital follow-up and remote digital monitoring.
Meanwhile, in the 12-month, multicenter TeleSpA study, which included 200 patients with any type of SpA, the number of hospital visits needed by people who were randomly assigned to receive patient-initiated care together with asynchronous telemonitoring was significantly lower than for the usual-care group, with no detriment to the participants’ overall health outcomes or safety. Moreover, the strategy was deemed cost-effective from a healthcare provision perspective.
Time to Rationalize Healthcare Resources?
People with chronic rheumatic diseases such as axSpA require long-term follow-up in specialist healthcare centers, Inger Jorid Berg, MD, PhD, of Diakonhjemmet Hospital in Oslo, Norway, said when she presented the findings of the ReMonit study as a late-breaking abstract.
“Traditionally, this has been offered as prescheduled face-to-face consultations at an outpatient clinic, but remote monitoring and patient-initiated care may allow for more targeted and efficient uses of healthcare resources,” Dr. Berg said.
“The end goal of what you’re trying to do is increase the efficiency of outpatient care and provide more patient-tailored care,” Kasper Hermans, MD, said in an interview. He presented the results of the TeleSpA study.
Dr. Hermans, who is a rheumatology fellow and PhD candidate at Maastricht University, Maastricht, the Netherlands, observed during his presentation at EULAR 2024 that there is an increasing demand for rheumatology services but an expected shortfall in the future workforce. Thus, “sustainable alternative strategies are needed for optimizing the efficiency of care,” he said.
People need to have timely access to care, Dr. Hermans stressed, but perhaps alternatives to the traditional models of care where patients are seen routinely every 6 or 12 months are needed, particularly as prior work had suggested that around one-third of people who were seen by a rheumatologist perhaps did not need to be.
A strategy of patient-initiated care — which is where people are seen by a healthcare provider only if they feel that they need to and request a consultation — is therefore an attractive proposition, particularly if it is backed up with remote monitoring, which is what the TeleSpA study was testing.
Two Distinct Studies
ReMonit and TeleSpA were two distinct studies. While both were noninferiority trials and involved patient-initiated care and telemonitoring of outpatients with SpA, that is where the similarities generally end.
Notably, ReMonit included a very specific population of patients — all had a diagnosis of axSpA and were being treated with a tumor necrosis factor (TNF) inhibitor and had been on a stable dose for the last 6 months. For inclusion, they also had to have inactive disease or low disease activity, as indicated by an Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1.
ReMonit’s telemonitoring strategy involved participants completing monthly questionnaires using the Dignio smartphone app. Patients first completed the Patient Global Assessment (PGA) and noted whether they had experienced a flare in their disease. If they had a flare or their PGA score was 3 or higher, then they were asked to also complete the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI). If the BASDAI score was 4 or more, then the patient was called by a study nurse and offered a consultation.
“Patients in all three groups were recommended to take blood samples at the general practitioner’s or at the hospital every third month as a safety procedure when using TNF inhibitors,” Dr. Berg said.
The primary outcome was the proportion of people who remained with low disease activity (ASDAS < 2.1) at 6, 12, and 18 months in each of the three arms of the trial, which were patient-initiated care (n = 81), monthly remote monitoring (n = 80), or usual follow-up in the hospital every 6 months (n = 82).
TeleSpA on the other hand was a “much more pragmatic trial, much closer to actual care,” Dr. Hermans said. “We included axial spondyloarthritis, peripheral spondyloarthritis, or patients who had both axial and peripheral disease, including patients with psoriatic arthritis,” he said, adding that their inclusion was regardless of their baseline ASDAS based on C-reactive protein (ASDAS-CRP).
This means that patients who would otherwise have been classified at baseline as having high disease activity (by ASDAS-CRP or similar disease activity measures) could be included. The main proviso was that both the patient and their rheumatologist had to define the condition as being stable with an acceptable level of symptom control and no immediate plans to change treatment within the next 3 months.
TeleSpA’s remote monitoring strategy involved the use of SpA-Net, which Dr. Hermans and coinvestigators have described previously as “an ongoing, disease-specific, prospective, web-based registry for monitoring SpA in daily practice.” This captures a host of clinical and laboratory test information.
SpA-Net was used in both arms of the study. However, while the 100 participants in the standard-care arm completed questionnaires and had tests before every in-person visit that had been prescheduled with their rheumatologist, the 100 individuals in the patient-initiated care arm had no prescheduled in-person visits except for being seen at the start and end of the study. These patients were reminded via email to complete the necessary SpA-Net registry questionnaires at 6 months.
The primary outcome for TeleSpA was the total number of rheumatology visits, including both physical and telephone or video consultations, within a 1-year period.
ReMonit Results
Berg reported that similar percentages of patients remained in a low disease activity state at 6, 12, and 18 months, regardless of the group that they had been randomized into, and that there was little change seen within the individual groups.
For instance, at 6, 12, and 18 months, 92%, 91%, and 92% of individuals in the patient-initiated arm had an ASDAS of < 2.1. Corresponding percentages for the usual-care arm were 96%, 93%, and 90% and for the remote-monitoring arm were 96%, 96%, and 94%.
Both patient-initiated care and remote monitoring were noninferior to usual care, and patient-initiated care was also noninferior to remote monitoring. There were no differences between the trial arms in terms of disease activity, measured using either ASDAS or BASDAI, at 6, 12, or 18 months.
Dr. Berg stated that “patient satisfaction was high in all three follow-up strategies, and there was the lowest resource use with patient-initiated care.” She concluded that “remote monitoring and patient-initiated care could be implemented in the follow-up of patients with axial spondyloarthritis and low disease activity.”
TeleSpA Results
In TeleSpA, people in the patient-initiated care and telemonitoring arm were seen a mean of 1.9 times over the course of the 1-year follow-up vs 2.6 for people in the usual care arm. The reduction was caused in part by the decrease in physical visits (1.4 vs 2.0) as there were the same mean number of telephone visits in each group. Overall, there was a 25.4% reduction in consultations comparing the patient-initiated care and telemonitoring arm with the usual-care arm.
Importantly, the intervention was noninferior regarding all of the predefined health outcomes: ASDAS, BASDAI, pain assessed using a visual analog scale, patient global assessment, and physician global assessment.
And more than 90% of participants in both groups reported having an overall good experience with their care.
Dr. Hermans noted after his presentation that an additional study had been performed where “we actively engaged with patients in the intervention group as well as healthcare providers to ask them what their experiences were with the intervention, how we could possibly improve it, and whether or not they thought that it was a valid approach to follow-up after the end of the study. And results were very, very reassuring.”
In terms of safety, eight serious adverse events were reported, but none were related to the study intervention, Dr. Hermans said.
Dr. Hermans reported that there was “negligible difference” in the 1-year quality-adjusted life-years (+0.004, in favor of the intervention overall) and that, while healthcare costs were lower at €243/year for the entire intervention period, societal costs were higher, at €513/year vs usual care. The latter was thought to be “due to an unexpected rise in absenteeism that we think was most likely due to a small amount of outliers,” Dr. Hermans said.
Nonetheless, using at willingness-to-pay threshold of €20,000/ quality-adjusted life year, he reported that the added value of patient-initiated care with remote monitoring yielded a potential net monetary benefit of +€322 from a healthcare perspective for the entire intervention period.
“We believe that these results support the fast-paced adoption of remote care interventions,” Dr. Hermans said. “In the context that I described earlier, of decreasing healthcare personnel and rising costs, we believe that this could be a valuable approach for follow-up for patients with stable axSpA.”
ReMonit was sponsored by Diakonhjemmet Hospital, and TeleSpA was sponsored by Maastricht University Medical Center, with funding from the Dutch Arthritis Society. Dr. Berg and Dr. Hermans had no relevant conflicts of interest to report.
A version of this article first appeared on Medscape.com.
Editor’s Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
VIENNA — People with spondyloarthritis (SpA) who have low or stable disease activity can effectively and safely be managed using a model of patient-initiated care with or without remote monitoring, suggested the results of two separate trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.
In the 18-month, single-center ReMonit study that included 243 people with axial SpA (axSpA), patient-initiated care was found to be noninferior for keeping them in a low-disease activity state, compared with both usual hospital follow-up and remote digital monitoring.
Meanwhile, in the 12-month, multicenter TeleSpA study, which included 200 patients with any type of SpA, the number of hospital visits needed by people who were randomly assigned to receive patient-initiated care together with asynchronous telemonitoring was significantly lower than for the usual-care group, with no detriment to the participants’ overall health outcomes or safety. Moreover, the strategy was deemed cost-effective from a healthcare provision perspective.
Time to Rationalize Healthcare Resources?
People with chronic rheumatic diseases such as axSpA require long-term follow-up in specialist healthcare centers, Inger Jorid Berg, MD, PhD, of Diakonhjemmet Hospital in Oslo, Norway, said when she presented the findings of the ReMonit study as a late-breaking abstract.
“Traditionally, this has been offered as prescheduled face-to-face consultations at an outpatient clinic, but remote monitoring and patient-initiated care may allow for more targeted and efficient uses of healthcare resources,” Dr. Berg said.
“The end goal of what you’re trying to do is increase the efficiency of outpatient care and provide more patient-tailored care,” Kasper Hermans, MD, said in an interview. He presented the results of the TeleSpA study.
Dr. Hermans, who is a rheumatology fellow and PhD candidate at Maastricht University, Maastricht, the Netherlands, observed during his presentation at EULAR 2024 that there is an increasing demand for rheumatology services but an expected shortfall in the future workforce. Thus, “sustainable alternative strategies are needed for optimizing the efficiency of care,” he said.
People need to have timely access to care, Dr. Hermans stressed, but perhaps alternatives to the traditional models of care where patients are seen routinely every 6 or 12 months are needed, particularly as prior work had suggested that around one-third of people who were seen by a rheumatologist perhaps did not need to be.
A strategy of patient-initiated care — which is where people are seen by a healthcare provider only if they feel that they need to and request a consultation — is therefore an attractive proposition, particularly if it is backed up with remote monitoring, which is what the TeleSpA study was testing.
Two Distinct Studies
ReMonit and TeleSpA were two distinct studies. While both were noninferiority trials and involved patient-initiated care and telemonitoring of outpatients with SpA, that is where the similarities generally end.
Notably, ReMonit included a very specific population of patients — all had a diagnosis of axSpA and were being treated with a tumor necrosis factor (TNF) inhibitor and had been on a stable dose for the last 6 months. For inclusion, they also had to have inactive disease or low disease activity, as indicated by an Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1.
ReMonit’s telemonitoring strategy involved participants completing monthly questionnaires using the Dignio smartphone app. Patients first completed the Patient Global Assessment (PGA) and noted whether they had experienced a flare in their disease. If they had a flare or their PGA score was 3 or higher, then they were asked to also complete the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI). If the BASDAI score was 4 or more, then the patient was called by a study nurse and offered a consultation.
“Patients in all three groups were recommended to take blood samples at the general practitioner’s or at the hospital every third month as a safety procedure when using TNF inhibitors,” Dr. Berg said.
The primary outcome was the proportion of people who remained with low disease activity (ASDAS < 2.1) at 6, 12, and 18 months in each of the three arms of the trial, which were patient-initiated care (n = 81), monthly remote monitoring (n = 80), or usual follow-up in the hospital every 6 months (n = 82).
TeleSpA on the other hand was a “much more pragmatic trial, much closer to actual care,” Dr. Hermans said. “We included axial spondyloarthritis, peripheral spondyloarthritis, or patients who had both axial and peripheral disease, including patients with psoriatic arthritis,” he said, adding that their inclusion was regardless of their baseline ASDAS based on C-reactive protein (ASDAS-CRP).
This means that patients who would otherwise have been classified at baseline as having high disease activity (by ASDAS-CRP or similar disease activity measures) could be included. The main proviso was that both the patient and their rheumatologist had to define the condition as being stable with an acceptable level of symptom control and no immediate plans to change treatment within the next 3 months.
TeleSpA’s remote monitoring strategy involved the use of SpA-Net, which Dr. Hermans and coinvestigators have described previously as “an ongoing, disease-specific, prospective, web-based registry for monitoring SpA in daily practice.” This captures a host of clinical and laboratory test information.
SpA-Net was used in both arms of the study. However, while the 100 participants in the standard-care arm completed questionnaires and had tests before every in-person visit that had been prescheduled with their rheumatologist, the 100 individuals in the patient-initiated care arm had no prescheduled in-person visits except for being seen at the start and end of the study. These patients were reminded via email to complete the necessary SpA-Net registry questionnaires at 6 months.
The primary outcome for TeleSpA was the total number of rheumatology visits, including both physical and telephone or video consultations, within a 1-year period.
ReMonit Results
Berg reported that similar percentages of patients remained in a low disease activity state at 6, 12, and 18 months, regardless of the group that they had been randomized into, and that there was little change seen within the individual groups.
For instance, at 6, 12, and 18 months, 92%, 91%, and 92% of individuals in the patient-initiated arm had an ASDAS of < 2.1. Corresponding percentages for the usual-care arm were 96%, 93%, and 90% and for the remote-monitoring arm were 96%, 96%, and 94%.
Both patient-initiated care and remote monitoring were noninferior to usual care, and patient-initiated care was also noninferior to remote monitoring. There were no differences between the trial arms in terms of disease activity, measured using either ASDAS or BASDAI, at 6, 12, or 18 months.
Dr. Berg stated that “patient satisfaction was high in all three follow-up strategies, and there was the lowest resource use with patient-initiated care.” She concluded that “remote monitoring and patient-initiated care could be implemented in the follow-up of patients with axial spondyloarthritis and low disease activity.”
TeleSpA Results
In TeleSpA, people in the patient-initiated care and telemonitoring arm were seen a mean of 1.9 times over the course of the 1-year follow-up vs 2.6 for people in the usual care arm. The reduction was caused in part by the decrease in physical visits (1.4 vs 2.0) as there were the same mean number of telephone visits in each group. Overall, there was a 25.4% reduction in consultations comparing the patient-initiated care and telemonitoring arm with the usual-care arm.
Importantly, the intervention was noninferior regarding all of the predefined health outcomes: ASDAS, BASDAI, pain assessed using a visual analog scale, patient global assessment, and physician global assessment.
And more than 90% of participants in both groups reported having an overall good experience with their care.
Dr. Hermans noted after his presentation that an additional study had been performed where “we actively engaged with patients in the intervention group as well as healthcare providers to ask them what their experiences were with the intervention, how we could possibly improve it, and whether or not they thought that it was a valid approach to follow-up after the end of the study. And results were very, very reassuring.”
In terms of safety, eight serious adverse events were reported, but none were related to the study intervention, Dr. Hermans said.
Dr. Hermans reported that there was “negligible difference” in the 1-year quality-adjusted life-years (+0.004, in favor of the intervention overall) and that, while healthcare costs were lower at €243/year for the entire intervention period, societal costs were higher, at €513/year vs usual care. The latter was thought to be “due to an unexpected rise in absenteeism that we think was most likely due to a small amount of outliers,” Dr. Hermans said.
Nonetheless, using at willingness-to-pay threshold of €20,000/ quality-adjusted life year, he reported that the added value of patient-initiated care with remote monitoring yielded a potential net monetary benefit of +€322 from a healthcare perspective for the entire intervention period.
“We believe that these results support the fast-paced adoption of remote care interventions,” Dr. Hermans said. “In the context that I described earlier, of decreasing healthcare personnel and rising costs, we believe that this could be a valuable approach for follow-up for patients with stable axSpA.”
ReMonit was sponsored by Diakonhjemmet Hospital, and TeleSpA was sponsored by Maastricht University Medical Center, with funding from the Dutch Arthritis Society. Dr. Berg and Dr. Hermans had no relevant conflicts of interest to report.
A version of this article first appeared on Medscape.com.
Editor’s Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
VIENNA — People with spondyloarthritis (SpA) who have low or stable disease activity can effectively and safely be managed using a model of patient-initiated care with or without remote monitoring, suggested the results of two separate trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.
In the 18-month, single-center ReMonit study that included 243 people with axial SpA (axSpA), patient-initiated care was found to be noninferior for keeping them in a low-disease activity state, compared with both usual hospital follow-up and remote digital monitoring.
Meanwhile, in the 12-month, multicenter TeleSpA study, which included 200 patients with any type of SpA, the number of hospital visits needed by people who were randomly assigned to receive patient-initiated care together with asynchronous telemonitoring was significantly lower than for the usual-care group, with no detriment to the participants’ overall health outcomes or safety. Moreover, the strategy was deemed cost-effective from a healthcare provision perspective.
Time to Rationalize Healthcare Resources?
People with chronic rheumatic diseases such as axSpA require long-term follow-up in specialist healthcare centers, Inger Jorid Berg, MD, PhD, of Diakonhjemmet Hospital in Oslo, Norway, said when she presented the findings of the ReMonit study as a late-breaking abstract.
“Traditionally, this has been offered as prescheduled face-to-face consultations at an outpatient clinic, but remote monitoring and patient-initiated care may allow for more targeted and efficient uses of healthcare resources,” Dr. Berg said.
“The end goal of what you’re trying to do is increase the efficiency of outpatient care and provide more patient-tailored care,” Kasper Hermans, MD, said in an interview. He presented the results of the TeleSpA study.
Dr. Hermans, who is a rheumatology fellow and PhD candidate at Maastricht University, Maastricht, the Netherlands, observed during his presentation at EULAR 2024 that there is an increasing demand for rheumatology services but an expected shortfall in the future workforce. Thus, “sustainable alternative strategies are needed for optimizing the efficiency of care,” he said.
People need to have timely access to care, Dr. Hermans stressed, but perhaps alternatives to the traditional models of care where patients are seen routinely every 6 or 12 months are needed, particularly as prior work had suggested that around one-third of people who were seen by a rheumatologist perhaps did not need to be.
A strategy of patient-initiated care — which is where people are seen by a healthcare provider only if they feel that they need to and request a consultation — is therefore an attractive proposition, particularly if it is backed up with remote monitoring, which is what the TeleSpA study was testing.
Two Distinct Studies
ReMonit and TeleSpA were two distinct studies. While both were noninferiority trials and involved patient-initiated care and telemonitoring of outpatients with SpA, that is where the similarities generally end.
Notably, ReMonit included a very specific population of patients — all had a diagnosis of axSpA and were being treated with a tumor necrosis factor (TNF) inhibitor and had been on a stable dose for the last 6 months. For inclusion, they also had to have inactive disease or low disease activity, as indicated by an Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1.
ReMonit’s telemonitoring strategy involved participants completing monthly questionnaires using the Dignio smartphone app. Patients first completed the Patient Global Assessment (PGA) and noted whether they had experienced a flare in their disease. If they had a flare or their PGA score was 3 or higher, then they were asked to also complete the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI). If the BASDAI score was 4 or more, then the patient was called by a study nurse and offered a consultation.
“Patients in all three groups were recommended to take blood samples at the general practitioner’s or at the hospital every third month as a safety procedure when using TNF inhibitors,” Dr. Berg said.
The primary outcome was the proportion of people who remained with low disease activity (ASDAS < 2.1) at 6, 12, and 18 months in each of the three arms of the trial, which were patient-initiated care (n = 81), monthly remote monitoring (n = 80), or usual follow-up in the hospital every 6 months (n = 82).
TeleSpA on the other hand was a “much more pragmatic trial, much closer to actual care,” Dr. Hermans said. “We included axial spondyloarthritis, peripheral spondyloarthritis, or patients who had both axial and peripheral disease, including patients with psoriatic arthritis,” he said, adding that their inclusion was regardless of their baseline ASDAS based on C-reactive protein (ASDAS-CRP).
This means that patients who would otherwise have been classified at baseline as having high disease activity (by ASDAS-CRP or similar disease activity measures) could be included. The main proviso was that both the patient and their rheumatologist had to define the condition as being stable with an acceptable level of symptom control and no immediate plans to change treatment within the next 3 months.
TeleSpA’s remote monitoring strategy involved the use of SpA-Net, which Dr. Hermans and coinvestigators have described previously as “an ongoing, disease-specific, prospective, web-based registry for monitoring SpA in daily practice.” This captures a host of clinical and laboratory test information.
SpA-Net was used in both arms of the study. However, while the 100 participants in the standard-care arm completed questionnaires and had tests before every in-person visit that had been prescheduled with their rheumatologist, the 100 individuals in the patient-initiated care arm had no prescheduled in-person visits except for being seen at the start and end of the study. These patients were reminded via email to complete the necessary SpA-Net registry questionnaires at 6 months.
The primary outcome for TeleSpA was the total number of rheumatology visits, including both physical and telephone or video consultations, within a 1-year period.
ReMonit Results
Berg reported that similar percentages of patients remained in a low disease activity state at 6, 12, and 18 months, regardless of the group that they had been randomized into, and that there was little change seen within the individual groups.
For instance, at 6, 12, and 18 months, 92%, 91%, and 92% of individuals in the patient-initiated arm had an ASDAS of < 2.1. Corresponding percentages for the usual-care arm were 96%, 93%, and 90% and for the remote-monitoring arm were 96%, 96%, and 94%.
Both patient-initiated care and remote monitoring were noninferior to usual care, and patient-initiated care was also noninferior to remote monitoring. There were no differences between the trial arms in terms of disease activity, measured using either ASDAS or BASDAI, at 6, 12, or 18 months.
Dr. Berg stated that “patient satisfaction was high in all three follow-up strategies, and there was the lowest resource use with patient-initiated care.” She concluded that “remote monitoring and patient-initiated care could be implemented in the follow-up of patients with axial spondyloarthritis and low disease activity.”
TeleSpA Results
In TeleSpA, people in the patient-initiated care and telemonitoring arm were seen a mean of 1.9 times over the course of the 1-year follow-up vs 2.6 for people in the usual care arm. The reduction was caused in part by the decrease in physical visits (1.4 vs 2.0) as there were the same mean number of telephone visits in each group. Overall, there was a 25.4% reduction in consultations comparing the patient-initiated care and telemonitoring arm with the usual-care arm.
Importantly, the intervention was noninferior regarding all of the predefined health outcomes: ASDAS, BASDAI, pain assessed using a visual analog scale, patient global assessment, and physician global assessment.
And more than 90% of participants in both groups reported having an overall good experience with their care.
Dr. Hermans noted after his presentation that an additional study had been performed where “we actively engaged with patients in the intervention group as well as healthcare providers to ask them what their experiences were with the intervention, how we could possibly improve it, and whether or not they thought that it was a valid approach to follow-up after the end of the study. And results were very, very reassuring.”
In terms of safety, eight serious adverse events were reported, but none were related to the study intervention, Dr. Hermans said.
Dr. Hermans reported that there was “negligible difference” in the 1-year quality-adjusted life-years (+0.004, in favor of the intervention overall) and that, while healthcare costs were lower at €243/year for the entire intervention period, societal costs were higher, at €513/year vs usual care. The latter was thought to be “due to an unexpected rise in absenteeism that we think was most likely due to a small amount of outliers,” Dr. Hermans said.
Nonetheless, using at willingness-to-pay threshold of €20,000/ quality-adjusted life year, he reported that the added value of patient-initiated care with remote monitoring yielded a potential net monetary benefit of +€322 from a healthcare perspective for the entire intervention period.
“We believe that these results support the fast-paced adoption of remote care interventions,” Dr. Hermans said. “In the context that I described earlier, of decreasing healthcare personnel and rising costs, we believe that this could be a valuable approach for follow-up for patients with stable axSpA.”
ReMonit was sponsored by Diakonhjemmet Hospital, and TeleSpA was sponsored by Maastricht University Medical Center, with funding from the Dutch Arthritis Society. Dr. Berg and Dr. Hermans had no relevant conflicts of interest to report.
A version of this article first appeared on Medscape.com.
Editor’s Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>VIENNA — People with spondyloarthritis (SpA) who have low or stable disease activity can effectively and safely be managed using a model of patient-initiated ca</metaDescription> <articlePDF/> <teaserImage>302061</teaserImage> <teaser>Patient-initiated care with or without remote monitoring for spondyloarthritis has been shown to work just as well as usual face-to-face care in two similar but very distinct trials.</teaser> <title>Patient-Driven Care Plus Telemonitoring Yields Promising Results for Spondyloarthritis</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">299</term> <term>183</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012a76.jpg</altRep> <description role="drol:caption">Dr. Inger Jorid Berg</description> <description role="drol:credit">Sara Freeman/Medscape Medical News</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012a77.jpg</altRep> <description role="drol:caption">Dr. Kasper Hermans</description> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Patient-Driven Care Plus Telemonitoring Yields Promising Results for Spondyloarthritis</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">VIENNA</span> — People with spondyloarthritis (SpA) who have low or stable disease activity can effectively and safely be managed using a model of patient-initiated care with or without remote monitoring, suggested the results of two separate trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting. </p> <p>In the 18-month, single-center <a href="https://clinicaltrials.gov/study/NCT05031767">ReMonit study</a> that included 243 people with axial SpA (axSpA), patient-initiated care was found to be noninferior for keeping them in a low-disease activity state, compared with both usual hospital follow-up and remote digital monitoring.<br/><br/>Meanwhile, in the 12-month, multicenter <a href="https://clinicaltrials.gov/study/NCT04673825">TeleSpA study</a>, which included 200 patients with any type of SpA, the number of hospital visits needed by people who were randomly assigned to receive patient-initiated care together with asynchronous telemonitoring was significantly lower than for the usual-care group, with no detriment to the participants’ overall health outcomes or safety. Moreover, the strategy was deemed cost-effective from a healthcare provision perspective.<br/><br/></p> <h2>Time to Rationalize Healthcare Resources?</h2> <p>People with chronic rheumatic diseases such as axSpA require long-term follow-up in specialist healthcare centers, <a href="https://en.remedy-senter.no/team/inger-jorid-berg">Inger Jorid Berg</a>, MD, PhD, of Diakonhjemmet Hospital in Oslo, Norway, said when she presented the findings of the ReMonit study as a <a href="https://ard.bmj.com/content/83/Suppl_1/234.2">late-breaking abstract</a>.</p> <p>[[{"fid":"302061","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Inger Jorid Berg, of Diakonhjemmet Hospital in Oslo, Norway","field_file_image_credit[und][0][value]":"Sara Freeman/Medscape Medical News","field_file_image_caption[und][0][value]":"Dr. Inger Jorid Berg"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]“Traditionally, this has been offered as prescheduled face-to-face consultations at an outpatient clinic, but remote monitoring and patient-initiated care may allow for more targeted and efficient uses of healthcare resources,” Dr. Berg said.<br/><br/>“The end goal of what you’re trying to do is increase the efficiency of outpatient care and provide more patient-tailored care,” <a href="https://cris.maastrichtuniversity.nl/en/persons/kasper-hermans">Kasper Hermans</a>, MD, said in an interview. He presented the <a href="https://ard.bmj.com/content/83/Suppl_1/148.1">results of the TeleSpA study</a>. <br/><br/>Dr. Hermans, who is a rheumatology fellow and PhD candidate at Maastricht University, Maastricht, the Netherlands, observed during his presentation at EULAR 2024 that there is an increasing demand for rheumatology services but an expected shortfall in the <a href="https://www.rheumatology.org.uk/news/details/Crisis-in-rheumatology-report-finds-dangerously-high-workforce-shortages">future workforce</a>. Thus, “sustainable alternative strategies are needed for optimizing the efficiency of care,” he said.<br/><br/>People need to have timely access to care, Dr. Hermans stressed, but perhaps alternatives to the traditional models of care where patients are seen routinely every 6 or 12 months are needed, particularly as <a href="https://www.jrheum.org/content/49/11/1214.long">prior work</a> had suggested that around one-third of people who were seen by a rheumatologist perhaps did not need to be.<br/><br/>A strategy of patient-initiated care — which is where people are seen by a healthcare provider only if they feel that they need to and request a consultation — is therefore an attractive proposition, particularly if it is backed up with remote monitoring, which is what the TeleSpA study was testing.<br/><br/></p> <h2>Two Distinct Studies</h2> <p>ReMonit and TeleSpA were two distinct studies. While both were noninferiority trials and involved patient-initiated care and telemonitoring of outpatients with SpA, that is where the similarities generally end.</p> <p>Notably, ReMonit included a very specific population of patients — all had a diagnosis of axSpA and were being treated with a tumor necrosis factor (TNF) inhibitor and had been on a stable dose for the last 6 months. For inclusion, they also had to have inactive disease or low disease activity, as indicated by an Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1.<br/><br/>ReMonit’s telemonitoring strategy involved participants completing monthly questionnaires using the Dignio smartphone app. Patients first completed the Patient Global Assessment (PGA) and noted whether they had experienced a flare in their disease. If they had a flare or their PGA score was 3 or higher, then they were asked to also complete the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI). If the BASDAI score was 4 or more, then the patient was called by a study nurse and offered a consultation.<br/><br/>“Patients in all three groups were recommended to take blood samples at the general practitioner’s or at the hospital every third month as a safety procedure when using TNF inhibitors,” Dr. Berg said.<br/><br/>The primary outcome was the proportion of people who remained with low disease activity (ASDAS < 2.1) at 6, 12, and 18 months in each of the three arms of the trial, which were patient-initiated care (n = 81), monthly remote monitoring (n = 80), or usual follow-up in the hospital every 6 months (n = 82).<br/><br/>TeleSpA on the other hand was a “much more pragmatic trial, much closer to actual care,” Dr. Hermans said. “We included axial spondyloarthritis, peripheral spondyloarthritis, or patients who had both axial and peripheral disease, including patients with psoriatic arthritis,” he said, adding that their inclusion was regardless of their baseline ASDAS based on C-reactive protein (ASDAS-CRP).<br/><br/>This means that patients who would otherwise have been classified at baseline as having high disease activity (by ASDAS-CRP or similar disease activity measures) could be included. The main proviso was that both the patient and their rheumatologist had to define the condition as being stable with an acceptable level of symptom control and no immediate plans to change treatment within the next 3 months.<br/><br/>[[{"fid":"302062","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Kasper Hermans"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]TeleSpA’s remote monitoring strategy involved the use of SpA-Net, which Dr. Hermans and coinvestigators have <a href="https://bmjopen.bmj.com/content/13/2/e067445">described previously</a> as “an ongoing, disease-specific, prospective, web-based registry for monitoring SpA in daily practice.” This captures a host of clinical and laboratory test information.<br/><br/>SpA-Net was used in both arms of the study. However, while the 100 participants in the standard-care arm completed questionnaires and had tests before every in-person visit that had been prescheduled with their rheumatologist, the 100 individuals in the patient-initiated care arm had no prescheduled in-person visits except for being seen at the start and end of the study. These patients were reminded via email to complete the necessary SpA-Net registry questionnaires at 6 months.<br/><br/>The primary outcome for TeleSpA was the total number of rheumatology visits, including both physical and telephone or video consultations, within a 1-year period. <br/><br/></p> <h2>ReMonit Results</h2> <p>Berg reported that similar percentages of patients remained in a low disease activity state at 6, 12, and 18 months, regardless of the group that they had been randomized into, and that there was little change seen within the individual groups.</p> <p>For instance, at 6, 12, and 18 months, 92%, 91%, and 92% of individuals in the patient-initiated arm had an ASDAS of < 2.1. Corresponding percentages for the usual-care arm were 96%, 93%, and 90% and for the remote-monitoring arm were 96%, 96%, and 94%.<br/><br/>Both patient-initiated care and remote monitoring were noninferior to usual care, and patient-initiated care was also noninferior to remote monitoring. There were no differences between the trial arms in terms of disease activity, measured using either ASDAS or BASDAI, at 6, 12, or 18 months.<br/><br/>Dr. Berg stated that “patient satisfaction was high in all three follow-up strategies, and there was the lowest resource use with patient-initiated care.” She concluded that “remote monitoring and patient-initiated care could be implemented in the follow-up of patients with axial spondyloarthritis and low disease activity.”<br/><br/></p> <h2>TeleSpA Results</h2> <p>In TeleSpA, people in the patient-initiated care and telemonitoring arm were seen a mean of 1.9 times over the course of the 1-year follow-up vs 2.6 for people in the usual care arm. The reduction was caused in part by the decrease in physical visits (1.4 vs 2.0) as there were the same mean number of telephone visits in each group. Overall, there was a 25.4% reduction in consultations comparing the patient-initiated care and telemonitoring arm with the usual-care arm.</p> <p>Importantly, the intervention was noninferior regarding all of the predefined health outcomes: ASDAS, BASDAI, pain assessed using a visual analog scale, patient global assessment, and physician global assessment.<br/><br/>And more than 90% of participants in both groups reported having an overall good experience with their care.<br/><br/>Dr. Hermans noted after his presentation that an <a href="https://ard.bmj.com/content/83/Suppl_1/894">additional study</a> had been performed where “we actively engaged with patients in the intervention group as well as healthcare providers to ask them what their experiences were with the intervention, how we could possibly improve it, and whether or not they thought that it was a valid approach to follow-up after the end of the study. And results were very, very reassuring.”<br/><br/>In terms of safety, eight serious adverse events were reported, but none were related to the study intervention, Dr. Hermans said. <br/><br/>Dr. Hermans reported that there was “negligible difference” in the 1-year quality-adjusted life-years (+0.004, in favor of the intervention overall) and that, while healthcare costs were lower at €243/year for the entire intervention period, societal costs were higher, at €513/year vs usual care. The latter was thought to be “due to an unexpected rise in absenteeism that we think was most likely due to a small amount of outliers,” Dr. Hermans said. <br/><br/>Nonetheless, using at willingness-to-pay threshold of €20,000/ quality-adjusted life year, he reported that the added value of patient-initiated care with remote monitoring yielded a potential net monetary benefit of +€322 from a healthcare perspective for the entire intervention period.<br/><br/>“We believe that these results support the fast-paced adoption of remote care interventions,” Dr. Hermans said. “In the context that I described earlier, of decreasing healthcare personnel and rising costs, we believe that this could be a valuable approach for follow-up for patients with stable axSpA.”<br/><br/>ReMonit was sponsored by Diakonhjemmet Hospital, and TeleSpA was sponsored by Maastricht University Medical Center, with funding from the Dutch Arthritis Society. Dr. Berg and Dr. Hermans had no relevant conflicts of interest to report.<span class="end"/></p> <p> <em>A version of this article first appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/patient-initiated-care-works-well-two-spondyloarthritis-2024a1000c37">Medscape.com</a></span>.<br/><br/>Editor’s Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM EULAR 2024
Latest Izokibep Trial for PsA Shows Promise But Misses on Enthesitis
VIENNA — The investigational interleukin (IL)-17 inhibitor izokibep hit its mark when it came to improving overall disease activity in people with active psoriatic arthritis (PsA) in a phase 2b/3 trial, but it was no better than placebo at reducing inflammation of the entheses.
This apparent and unexpected lack of effect in the entheses was a key talking point after Philip J. Mease, MD, presented the late-breaking trial findings at the annual European Congress of Rheumatology.
At just 18.6 kilodaltons in size, izokibep is just “one tenth the size of a standard monoclonal antibody” and is classed as a small protein therapeutic, Dr. Mease said. It has a “very tight” binding affinity for IL-17A, and because it also binds to albumin, it has a prolonged half-life compared with other IL-17 inhibitors. Potentially, it should be able to “penetrate into difficult areas,” such as the entheses, he said.
Prespecified Enthesitis Analysis
However, results of a prespecified secondary analysis conducted in 209 of the 343 trial participants who had received treatment showed no significant difference in the proportions with enthesis resolution at 16 weeks, defined as a Leeds Enthesitis Index (LEI) of 0.
Comparing two dosing regimens of izokibep 160 mg once weekly (QW) vs every other week (Q2W) with placebo, enthesitis resolution was seen in 45%, 56%, and 47%, respectively, of patients.
The LEI is “sometimes subject to problems with evaluation because of placebo response, which is what we see here,” noted Dr. Mease, director of rheumatology research at the Providence Swedish Medical Center and a rheumatology professor at the University of Washington School of Medicine in Seattle.
An exploratory analysis showed that there was a better response for izokibep vs placebo if the analysis included only patients with higher LEI scores at baseline, at 8.0% (n = 12) for placebo, 22.0% (n = 9) for izokibep 160 mg QW, and 50.0% (n = 12) for izokibep 160 mg Q2W.
Main Efficacy Data
The primary endpoint for the trial was the proportion of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks. This showed a clear advantage for treatment with izokibep 160 QW and Q2W compared with placebo, with a respective 40%, 43%, and 15% of patients meeting this endpoint.
Corresponding ACR20 response rates were 59%, 64%, and 35%, respectively; ACR70 response rates were a respective 25%, 23%, and 5%.
In addition to ACR70, izokibep 160 QW and Q2W met a number of other “high hurdle” efficacy endpoints better than did placebo, Dr. Mease reported. A 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI90) was achieved by a respective 64%, 58%, and 12% of patients, and a 100% reduction in this index (PASI100) was achieved by a respective 51%, 47%, and 12%. And 41%, 42%, and 14% of patients, respectively, met the criteria for minimal disease activity.
Patient Population
Mease pointed out during his presentation that the trial included patients with adult-onset PsA that had been ongoing for ≥ 6 months. Patients had to have at least three tender or swollen joints and an inadequate response, intolerance, or contraindication to commonly used front-line therapies such as nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and tumor necrosis factor inhibitors (TNFi).
In fact, around half of the participants across the three treatment arms had received prior csDMARDs, and almost a quarter had received a TNFi.
The mean duration of disease was around 7 years, the average age was about 50 years, and the majority of the participants were White individuals. There were more women than men in the placebo vs the izokibep arms (43.4% vs about 60.0%).
Adverse Events
Injection site reactions were the most common adverse events, most of which were mild to moderate. Very few (< 1% to 4%) led to any need to discontinue the drug.
Serious adverse events occurred at low rates in all study arms: 0.8% for placebo, 2.7% for izokibep QW, and 1.8% for izokibep Q2W.
One patient each (0.9%) in the izokibep arms developed ulcerative colitis, whereas none in the placebo group did. Only two patients developed candidiasis. One was in the placebo group and had a skin infection, and the other was an oral infection in the QW izokibep arm.
There were no cases of uveitis, suicidal ideation, or deaths reported.
Comments on the Study
During the discussion that followed the presentation, Walter P. Maksymowych, MBChB, of the University of Alberta in Edmonton, Alberta, Canada, addressed the dosing regimens used.
“Looking at the side effect profile and then looking at the response rate, comparing the weekly dosing and every 2 weeks, do you think, in hindsight, you might be remiss that there wasn’t an additional dosing on a monthly basis, especially since this is a construct that is meant to prolong the half-life of the molecule?” he asked, adding that perhaps this should be something to consider in future studies.
Mease responded that there had been a fourth dosing arm in the trial — izokibep 80 mg once a month — but because there were only eight patients, the data were not sufficiently robust to analyze.
Commenting on the study, Laura C. Coates, MBChB, PhD, said: “It’s a pretty standard phase 2b/3 study,” and the outcomes were not wildly different from what has been seen with other IL-17A inhibitors.
“In phase 2, the enthesitis data looked really good; in phase 3, the enthesitis data looks the same as for any other IL-17 inhibitor,” Dr. Coates said.
More and longer-term data are needed to see if “the theoretical biological difference in the drug design translates to a different clinical outcome or whether it’s another IL-17,” added Dr. Coates, a clinician scientist and senior clinical research fellow at the University of Oxford in England.
Dennis McGonagle, MB MCH BAO, PhD, of the University of Leeds, England, also picked up on the enthesitis data, echoing the conclusion that the phase 2 enthesitis data were “spectacular” and noting that “it’s a real inversion of what was expected, given the small molecule.”
The study was funded by Acelyrin. Dr. Mease disclosed ties with Acelyrin and other pharmaceutical companies. Dr. Maksymowych, Dr. Coates, and Dr. McGonagle reported having a variety of financial relationships with pharmaceutical companies outside of this study.
A version of this article appeared on Medscape.com.
VIENNA — The investigational interleukin (IL)-17 inhibitor izokibep hit its mark when it came to improving overall disease activity in people with active psoriatic arthritis (PsA) in a phase 2b/3 trial, but it was no better than placebo at reducing inflammation of the entheses.
This apparent and unexpected lack of effect in the entheses was a key talking point after Philip J. Mease, MD, presented the late-breaking trial findings at the annual European Congress of Rheumatology.
At just 18.6 kilodaltons in size, izokibep is just “one tenth the size of a standard monoclonal antibody” and is classed as a small protein therapeutic, Dr. Mease said. It has a “very tight” binding affinity for IL-17A, and because it also binds to albumin, it has a prolonged half-life compared with other IL-17 inhibitors. Potentially, it should be able to “penetrate into difficult areas,” such as the entheses, he said.
Prespecified Enthesitis Analysis
However, results of a prespecified secondary analysis conducted in 209 of the 343 trial participants who had received treatment showed no significant difference in the proportions with enthesis resolution at 16 weeks, defined as a Leeds Enthesitis Index (LEI) of 0.
Comparing two dosing regimens of izokibep 160 mg once weekly (QW) vs every other week (Q2W) with placebo, enthesitis resolution was seen in 45%, 56%, and 47%, respectively, of patients.
The LEI is “sometimes subject to problems with evaluation because of placebo response, which is what we see here,” noted Dr. Mease, director of rheumatology research at the Providence Swedish Medical Center and a rheumatology professor at the University of Washington School of Medicine in Seattle.
An exploratory analysis showed that there was a better response for izokibep vs placebo if the analysis included only patients with higher LEI scores at baseline, at 8.0% (n = 12) for placebo, 22.0% (n = 9) for izokibep 160 mg QW, and 50.0% (n = 12) for izokibep 160 mg Q2W.
Main Efficacy Data
The primary endpoint for the trial was the proportion of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks. This showed a clear advantage for treatment with izokibep 160 QW and Q2W compared with placebo, with a respective 40%, 43%, and 15% of patients meeting this endpoint.
Corresponding ACR20 response rates were 59%, 64%, and 35%, respectively; ACR70 response rates were a respective 25%, 23%, and 5%.
In addition to ACR70, izokibep 160 QW and Q2W met a number of other “high hurdle” efficacy endpoints better than did placebo, Dr. Mease reported. A 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI90) was achieved by a respective 64%, 58%, and 12% of patients, and a 100% reduction in this index (PASI100) was achieved by a respective 51%, 47%, and 12%. And 41%, 42%, and 14% of patients, respectively, met the criteria for minimal disease activity.
Patient Population
Mease pointed out during his presentation that the trial included patients with adult-onset PsA that had been ongoing for ≥ 6 months. Patients had to have at least three tender or swollen joints and an inadequate response, intolerance, or contraindication to commonly used front-line therapies such as nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and tumor necrosis factor inhibitors (TNFi).
In fact, around half of the participants across the three treatment arms had received prior csDMARDs, and almost a quarter had received a TNFi.
The mean duration of disease was around 7 years, the average age was about 50 years, and the majority of the participants were White individuals. There were more women than men in the placebo vs the izokibep arms (43.4% vs about 60.0%).
Adverse Events
Injection site reactions were the most common adverse events, most of which were mild to moderate. Very few (< 1% to 4%) led to any need to discontinue the drug.
Serious adverse events occurred at low rates in all study arms: 0.8% for placebo, 2.7% for izokibep QW, and 1.8% for izokibep Q2W.
One patient each (0.9%) in the izokibep arms developed ulcerative colitis, whereas none in the placebo group did. Only two patients developed candidiasis. One was in the placebo group and had a skin infection, and the other was an oral infection in the QW izokibep arm.
There were no cases of uveitis, suicidal ideation, or deaths reported.
Comments on the Study
During the discussion that followed the presentation, Walter P. Maksymowych, MBChB, of the University of Alberta in Edmonton, Alberta, Canada, addressed the dosing regimens used.
“Looking at the side effect profile and then looking at the response rate, comparing the weekly dosing and every 2 weeks, do you think, in hindsight, you might be remiss that there wasn’t an additional dosing on a monthly basis, especially since this is a construct that is meant to prolong the half-life of the molecule?” he asked, adding that perhaps this should be something to consider in future studies.
Mease responded that there had been a fourth dosing arm in the trial — izokibep 80 mg once a month — but because there were only eight patients, the data were not sufficiently robust to analyze.
Commenting on the study, Laura C. Coates, MBChB, PhD, said: “It’s a pretty standard phase 2b/3 study,” and the outcomes were not wildly different from what has been seen with other IL-17A inhibitors.
“In phase 2, the enthesitis data looked really good; in phase 3, the enthesitis data looks the same as for any other IL-17 inhibitor,” Dr. Coates said.
More and longer-term data are needed to see if “the theoretical biological difference in the drug design translates to a different clinical outcome or whether it’s another IL-17,” added Dr. Coates, a clinician scientist and senior clinical research fellow at the University of Oxford in England.
Dennis McGonagle, MB MCH BAO, PhD, of the University of Leeds, England, also picked up on the enthesitis data, echoing the conclusion that the phase 2 enthesitis data were “spectacular” and noting that “it’s a real inversion of what was expected, given the small molecule.”
The study was funded by Acelyrin. Dr. Mease disclosed ties with Acelyrin and other pharmaceutical companies. Dr. Maksymowych, Dr. Coates, and Dr. McGonagle reported having a variety of financial relationships with pharmaceutical companies outside of this study.
A version of this article appeared on Medscape.com.
VIENNA — The investigational interleukin (IL)-17 inhibitor izokibep hit its mark when it came to improving overall disease activity in people with active psoriatic arthritis (PsA) in a phase 2b/3 trial, but it was no better than placebo at reducing inflammation of the entheses.
This apparent and unexpected lack of effect in the entheses was a key talking point after Philip J. Mease, MD, presented the late-breaking trial findings at the annual European Congress of Rheumatology.
At just 18.6 kilodaltons in size, izokibep is just “one tenth the size of a standard monoclonal antibody” and is classed as a small protein therapeutic, Dr. Mease said. It has a “very tight” binding affinity for IL-17A, and because it also binds to albumin, it has a prolonged half-life compared with other IL-17 inhibitors. Potentially, it should be able to “penetrate into difficult areas,” such as the entheses, he said.
Prespecified Enthesitis Analysis
However, results of a prespecified secondary analysis conducted in 209 of the 343 trial participants who had received treatment showed no significant difference in the proportions with enthesis resolution at 16 weeks, defined as a Leeds Enthesitis Index (LEI) of 0.
Comparing two dosing regimens of izokibep 160 mg once weekly (QW) vs every other week (Q2W) with placebo, enthesitis resolution was seen in 45%, 56%, and 47%, respectively, of patients.
The LEI is “sometimes subject to problems with evaluation because of placebo response, which is what we see here,” noted Dr. Mease, director of rheumatology research at the Providence Swedish Medical Center and a rheumatology professor at the University of Washington School of Medicine in Seattle.
An exploratory analysis showed that there was a better response for izokibep vs placebo if the analysis included only patients with higher LEI scores at baseline, at 8.0% (n = 12) for placebo, 22.0% (n = 9) for izokibep 160 mg QW, and 50.0% (n = 12) for izokibep 160 mg Q2W.
Main Efficacy Data
The primary endpoint for the trial was the proportion of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks. This showed a clear advantage for treatment with izokibep 160 QW and Q2W compared with placebo, with a respective 40%, 43%, and 15% of patients meeting this endpoint.
Corresponding ACR20 response rates were 59%, 64%, and 35%, respectively; ACR70 response rates were a respective 25%, 23%, and 5%.
In addition to ACR70, izokibep 160 QW and Q2W met a number of other “high hurdle” efficacy endpoints better than did placebo, Dr. Mease reported. A 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI90) was achieved by a respective 64%, 58%, and 12% of patients, and a 100% reduction in this index (PASI100) was achieved by a respective 51%, 47%, and 12%. And 41%, 42%, and 14% of patients, respectively, met the criteria for minimal disease activity.
Patient Population
Mease pointed out during his presentation that the trial included patients with adult-onset PsA that had been ongoing for ≥ 6 months. Patients had to have at least three tender or swollen joints and an inadequate response, intolerance, or contraindication to commonly used front-line therapies such as nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and tumor necrosis factor inhibitors (TNFi).
In fact, around half of the participants across the three treatment arms had received prior csDMARDs, and almost a quarter had received a TNFi.
The mean duration of disease was around 7 years, the average age was about 50 years, and the majority of the participants were White individuals. There were more women than men in the placebo vs the izokibep arms (43.4% vs about 60.0%).
Adverse Events
Injection site reactions were the most common adverse events, most of which were mild to moderate. Very few (< 1% to 4%) led to any need to discontinue the drug.
Serious adverse events occurred at low rates in all study arms: 0.8% for placebo, 2.7% for izokibep QW, and 1.8% for izokibep Q2W.
One patient each (0.9%) in the izokibep arms developed ulcerative colitis, whereas none in the placebo group did. Only two patients developed candidiasis. One was in the placebo group and had a skin infection, and the other was an oral infection in the QW izokibep arm.
There were no cases of uveitis, suicidal ideation, or deaths reported.
Comments on the Study
During the discussion that followed the presentation, Walter P. Maksymowych, MBChB, of the University of Alberta in Edmonton, Alberta, Canada, addressed the dosing regimens used.
“Looking at the side effect profile and then looking at the response rate, comparing the weekly dosing and every 2 weeks, do you think, in hindsight, you might be remiss that there wasn’t an additional dosing on a monthly basis, especially since this is a construct that is meant to prolong the half-life of the molecule?” he asked, adding that perhaps this should be something to consider in future studies.
Mease responded that there had been a fourth dosing arm in the trial — izokibep 80 mg once a month — but because there were only eight patients, the data were not sufficiently robust to analyze.
Commenting on the study, Laura C. Coates, MBChB, PhD, said: “It’s a pretty standard phase 2b/3 study,” and the outcomes were not wildly different from what has been seen with other IL-17A inhibitors.
“In phase 2, the enthesitis data looked really good; in phase 3, the enthesitis data looks the same as for any other IL-17 inhibitor,” Dr. Coates said.
More and longer-term data are needed to see if “the theoretical biological difference in the drug design translates to a different clinical outcome or whether it’s another IL-17,” added Dr. Coates, a clinician scientist and senior clinical research fellow at the University of Oxford in England.
Dennis McGonagle, MB MCH BAO, PhD, of the University of Leeds, England, also picked up on the enthesitis data, echoing the conclusion that the phase 2 enthesitis data were “spectacular” and noting that “it’s a real inversion of what was expected, given the small molecule.”
The study was funded by Acelyrin. Dr. Mease disclosed ties with Acelyrin and other pharmaceutical companies. Dr. Maksymowych, Dr. Coates, and Dr. McGonagle reported having a variety of financial relationships with pharmaceutical companies outside of this study.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>VIENNA — The investigational interleukin (IL)-17 inhibitor izokibep hit its mark when it came to improving overall disease activity in people with active psoria</metaDescription> <articlePDF/> <teaserImage>301946</teaserImage> <teaser>The primary efficacy endpoint was met, but the novel small molecule therapeutic did not reduce enthesitis more than placebo, as might have been expected.</teaser> <title>Latest Izokibep Trial for PsA Shows Promise But Misses on Enthesitis</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>skin</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>13</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">282</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012a45.jpg</altRep> <description role="drol:caption">Dr. Philip J. Mease</description> <description role="drol:credit">Sara Freeman/Medscape Medical News</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2400e1b2.jpg</altRep> <description role="drol:caption">Dr. Walter P. Maksymowych</description> <description role="drol:credit"/> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2400a03b.jpg</altRep> <description role="drol:caption">Dr. Laura C. Coates</description> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Latest Izokibep Trial for PsA Shows Promise But Misses on Enthesitis</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">VIENNA</span> — The investigational interleukin (IL)-17 inhibitor izokibep hit its mark when it came to improving overall disease activity in people with active psoriatic arthritis (PsA) in a phase 2b/3 trial, but it was no better than placebo at reducing inflammation of the entheses. </p> <p>This apparent and unexpected lack of effect in the entheses was a key talking point after <span class="Hyperlink"><a href="https://www.swedish.org/doctors/rheumatology/wa/seattle/philip-mease-1336218171">Philip J. Mease</a></span>, MD, presented the <span class="Hyperlink"><a href="https://ard.bmj.com/content/83/Suppl_1/235">late-breaking trial findings</a></span> at the annual European Congress of Rheumatology.<br/><br/>[[{"fid":"301946","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Philip J. Mease, director of Rheumatology Research at the Providence Swedish Medical Center and a rheumatology professor at the University of Washington School of Medicine in Seattle","field_file_image_credit[und][0][value]":"Sara Freeman/Medscape Medical News","field_file_image_caption[und][0][value]":"Dr. Philip J. Mease"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]At just 18.6 kilodaltons in size, izokibep is just “one tenth the size of a standard monoclonal antibody” and is classed as a small protein therapeutic, Dr. Mease said. It has a “very tight” binding affinity for IL-17A, and because it also binds to albumin, it has a prolonged half-life compared with other IL-17 inhibitors. Potentially, it should be able to “penetrate into difficult areas,” such as the entheses, he said.<br/><br/></p> <h2>Prespecified Enthesitis Analysis</h2> <p>However, results of a prespecified secondary analysis conducted in 209 of the 343 trial participants who had received treatment showed no significant difference in the proportions with enthesis resolution at 16 weeks, defined as a Leeds Enthesitis Index (LEI) of 0.</p> <p>Comparing two dosing regimens of izokibep 160 mg once weekly (QW) vs every other week (Q2W) with placebo, enthesitis resolution was seen in 45%, 56%, and 47%, respectively, of patients.<br/><br/>The LEI is “sometimes subject to problems with evaluation because of placebo response, which is what we see here,” noted Dr. Mease, director of rheumatology research at the Providence Swedish Medical Center and a rheumatology professor at the University of Washington School of Medicine in Seattle.<br/><br/>An exploratory analysis showed that there was a better response for izokibep vs placebo if the analysis included only patients with higher LEI scores at baseline, at 8.0% (n = 12) for placebo, 22.0% (n = 9) for izokibep 160 mg QW, and 50.0% (n = 12) for izokibep 160 mg Q2W.<br/><br/></p> <h2>Main Efficacy Data</h2> <p>The primary endpoint for the trial was the proportion of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks. This showed a clear advantage for treatment with izokibep 160 QW and Q2W compared with placebo, with a respective 40%, 43%, and 15% of patients meeting this endpoint.</p> <p>Corresponding ACR20 response rates were 59%, 64%, and 35%, respectively; ACR70 response rates were a respective 25%, 23%, and 5%.<br/><br/>In addition to ACR70, izokibep 160 QW and Q2W met a number of other “high hurdle” efficacy endpoints better than did placebo, Dr. Mease reported. A 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI90) was achieved by a respective 64%, 58%, and 12% of patients, and a 100% reduction in this index (PASI100) was achieved by a respective 51%, 47%, and 12%. And 41%, 42%, and 14% of patients, respectively, met the criteria for minimal disease activity.<br/><br/></p> <h2>Patient Population</h2> <p>Mease pointed out during his presentation that the trial included patients with adult-onset PsA that had been ongoing for ≥ 6 months. Patients had to have at least three tender or swollen joints and an inadequate response, intolerance, or contraindication to commonly used front-line therapies such as nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and tumor necrosis factor inhibitors (TNFi).</p> <p>In fact, around half of the participants across the three treatment arms had received prior csDMARDs, and almost a quarter had received a TNFi.<br/><br/>The mean duration of disease was around 7 years, the average age was about 50 years, and the majority of the participants were White individuals. There were more women than men in the placebo vs the izokibep arms (43.4% vs about 60.0%).<br/><br/></p> <h2>Adverse Events</h2> <p>Injection site reactions were the most common adverse events, most of which were mild to moderate. Very few (< 1% to 4%) led to any need to discontinue the drug.</p> <p>Serious adverse events occurred at low rates in all study arms: 0.8% for placebo, 2.7% for izokibep QW, and 1.8% for izokibep Q2W.<br/><br/>One patient each (0.9%) in the izokibep arms developed ulcerative colitis, whereas none in the placebo group did. Only two patients developed candidiasis. One was in the placebo group and had a skin infection, and the other was an oral infection in the QW izokibep arm.<br/><br/>There were no cases of uveitis, suicidal ideation, or deaths reported.<br/><br/></p> <h2>Comments on the Study</h2> <p>During the discussion that followed the presentation, <span class="Hyperlink"><a href="https://apps.ualberta.ca/directory/person/maksymow">Walter P. Maksymowych</a></span>, MBChB, of the University of Alberta in Edmonton, Alberta, Canada, addressed the dosing regimens used.</p> <p>[[{"fid":"262551","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Walter P. Maksymowych is chief medical officer of CARE Arthritis and professor in rheumatology at the University of Alberta in Edmonton, Canada","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Walter P. Maksymowych"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]“Looking at the side effect profile and then looking at the response rate, comparing the weekly dosing and every 2 weeks, do you think, in hindsight, you might be remiss that there wasn’t an additional dosing on a monthly basis, especially since this is a construct that is meant to prolong the half-life of the molecule?” he asked, adding that perhaps this should be something to consider in future studies.<br/><br/>Mease responded that there had been a fourth dosing arm in the trial — izokibep 80 mg once a month — but because there were only eight patients, the data were not sufficiently robust to analyze. <br/><br/>Commenting on the study, <span class="Hyperlink"><a href="https://www.ndorms.ox.ac.uk/team/laura-coates">Laura C. Coates</a></span>, MBChB, PhD, said: “It’s a pretty standard phase 2b/3 study,” and the outcomes were not wildly different from what has been seen with other IL-17A inhibitors.<br/><br/>“In <span class="Hyperlink"><a href="https://clinicaltrials.gov/study/NCT04713072">phase 2</a></span>, the enthesitis data looked really good; in phase 3, the enthesitis data looks the same as for any other IL-17 inhibitor,” Dr. Coates said.[[{"fid":"221015","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Laura C. Coates, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford (England)","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Laura C. Coates"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]<br/><br/>More and longer-term data are needed to see if “the theoretical biological difference in the drug design translates to a different clinical outcome or whether it’s another IL-17,” added Dr. Coates, a clinician scientist and senior clinical research fellow at the University of Oxford in England.<br/><br/><span class="Hyperlink"><a href="https://medicinehealth.leeds.ac.uk/medicine/staff/2524/professor-dennis-mcgonagle">Dennis McGonagle</a></span>, MB MCH BAO, PhD, of the University of Leeds, England, also picked up on the enthesitis data, echoing the conclusion that the phase 2 enthesitis data were “spectacular” and noting that “it’s a real inversion of what was expected, given the small molecule.”<br/><br/>The study was funded by Acelyrin. Dr. Mease disclosed ties with Acelyrin and other pharmaceutical companies. Dr. Maksymowych, Dr. Coates, and Dr. McGonagle reported having a variety of financial relationships with pharmaceutical companies outside of this study.<br/><br/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/izokibep-enthesitis-benefit-lacking-phase-2b-3-psa-trial-2024a1000be9">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM EULAR 2024
Selective JAK 1 Inhibitor for RA Proves Promising in Phase 3 Trial
VIENNA — The highly selective oral Janus kinase (JAK) inhibitor SHR0302 (ivarmacitinib) enables more patients with active rheumatoid arthritis to meet American College of Rheumatology (ACR) response criteria than placebo, the results of a phase 3 trial showed.
After 24 weeks of daily treatment, the primary endpoint of an ACR20 response was met by 40.4% of those who had been given placebo, 70.4% who had received a 4-mg dose, and 75.1% given an 8-mg dose. At the same time point, ACR50 responses were a respective 15.4%, 46.0%, and 57.1%, and ACR70 responses were 6.9%, 22.2%, and 31.7%. All analyses comparing SHR0302 vs placebo were highly significant (P < .0001).
First Phase 3 Trial in China
“This is the first highly selective JAK inhibitor originally developed, and a phase 3 clinical trial conducted, [exclusively] in China,” Jinjing Liu, from the department of rheumatology at Peking Union Medical College Hospital in Beijing, China, said in an interview.
Ms. Liu presented the results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, during the Abstract Plenary, which highlights the best-scored abstracts of the meeting.
“We are working our best to provide more choices for Chinese patients,” Ms. Liu said, which includes lowering the financial cost of treatments. A locally developed JAK inhibitor could potentially be a much cheaper option than other alternatives that are currently available, she said.
But it is more than that, Ms. Liu said. “The selectivity of SHR0302 for JAK 1 is nine times greater than for JAK 2, so it surpasses either tofacitinib or baricitinib.” The theory is that this higher selectivity for JAK 1 over JAK 2 could lead to fewer adverse events (AEs).
“Maybe it will result in lower JAK 2–associated hematologic side effects,” Ms. Liu said.
“We have noticed that, throughout the clinical trial, the most commonly reported AEs in the drug groups were upper extremity infection [21.7%-22.8% vs 13.8% for placebo] and hyperlipidemia [12.2%-15.3% vs 5.3%].” And for the control group, she said that anemia was the second highest reported AE, at 11.7% vs 6.3% and 7.4% for SHR0302 4 and 8 mg, respectively.
Standard Design
The trial design was typical for a phase 3 study: Multicenter, randomized, placebo controlled, and double blind for the first 24 weeks, followed by an extension period out to 52 weeks. For inclusion in the study, patients had to be aged 18-75 years and have active rheumatoid arthritis and an inadequate response to previous treatment with conventional synthetic disease-modifying antirheumatic drugs.
Of 1085 patients who were initially screened, 566 were randomly allocated to receive placebo (n = 188), SHR0302 4 mg (n = 189), or SHR0302 8 mg (n = 189). The average age of patients was 51 years, and 13.3% of patients were older than 65 years.
Additional Results
Alongside improvements in ACR responses, Ms Liu reported that a significantly higher proportion of patients treated with SHR0302 vs placebo achieved a Disease Activity Score in 28 joints based on C-reactive protein less than 2.6 (29.6% with 4 mg and 39.2% with 8 mg vs 4.2% with placebo; both P < .0001) and at least 3.2 (57.1% and 46.0% vs 15.4%; both P < .0001) at 24 weeks.
There were also greater improvements seen in Health Assessment Questionnaire-Disability Index, 36-item Short-Form (SF36) physical component summary, and SF36 mental component summary scores for active vs placebo treatment.
As for AEs, there were no surprises. During the main 24-week trial period, 81.5%, 90.5%, and 79.3% of patients treated with SHR0302 4 and 8 mg and placebo, respectively, experienced any AE.
Infection-related treatment-emergent adverse effects occurred slightly more often in the SHR0302-treated groups (40.2% for 4 mg and 40.7% for 8 mg) than in the placebo group (34.0%). There was a single case of serious infection that required treatment in the SHR0302 8 mg–treated group but no cases of systemic opportunistic infection.
There was one thromboembolic event and one major cardiovascular event in the 24-week period, both occurring in patients treated with SHR0302 8 mg. There were also single cases of each reported during the extension phase of the trial, but both were in the placebo arm.
Two cases of liver function abnormality — one each in the SHR0302 4- and 8-mg groups — were recorded during the main part of the trial and two cases — both in the SHR0302 4-mg group — during the extension phase.
As for malignancy, there was a single, newly diagnosed case in the SHR0302 4 mg group in the first part of the trial and two cases, both in the SHR0302 4-mg group, during the extension phase.
“We hope this [JAK inhibitor] will be for everybody. But, you know, if it’s for patients, globally, more clinical trials would be required,” Ms. Liu said in an interview. The future, she added, was to start accumulating some real-world data and perhaps do a trial comparing SHR0302 with another JAK inhibitor or a tumor necrosis factor inhibitor.
Another JAK in the Box?
Following her presentation, Ms. Liu at EULAR 2024 was quizzed as to why there were so many screening failures. She responded that she did not have the full data to answer the question but noted that some patients in her center had been worried about being randomized to a placebo. This trial has also been conducted during the COVID-19 pandemic, so that may have been a contributing factor with patients unable to get to their follow-up appointments.
Iain B. McInnes, MD, PhD, vice principal, professor of rheumatology, and head of the College of Medical, Veterinary & Life Sciences at the University of Glasgow, Glasgow, Scotland, commented on the study, saying: “The JAK field is in evolution. We need to understand the broader toxicities. There is an unexplained mechanism driving potential cardiovascular and malignant risk in a small proportion of patients receiving the drugs.”
Dr. McInnes added, “It’s really unclear whether the solution is going to be greater selectivity and potency, or whether we need to think really about selecting the right patients for a JAK inhibitor.”
The study was funded by Jiangsu Hengrui Pharmaceuticals. Two of the 18 authors of the abstract were employees of the sponsoring company, but Ms. Liu reported having no conflicts of interest. Dr. McInnes reported serving on speaker’s bureaus for AbbVie and UCB; receiving consulting fees received from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Eli Lilly, Evelo, Gilead, Janssen, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB; and receiving grant/research support from GlaxoSmithKline, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, and UCB.
A version of this article appeared on Medscape.com.
VIENNA — The highly selective oral Janus kinase (JAK) inhibitor SHR0302 (ivarmacitinib) enables more patients with active rheumatoid arthritis to meet American College of Rheumatology (ACR) response criteria than placebo, the results of a phase 3 trial showed.
After 24 weeks of daily treatment, the primary endpoint of an ACR20 response was met by 40.4% of those who had been given placebo, 70.4% who had received a 4-mg dose, and 75.1% given an 8-mg dose. At the same time point, ACR50 responses were a respective 15.4%, 46.0%, and 57.1%, and ACR70 responses were 6.9%, 22.2%, and 31.7%. All analyses comparing SHR0302 vs placebo were highly significant (P < .0001).
First Phase 3 Trial in China
“This is the first highly selective JAK inhibitor originally developed, and a phase 3 clinical trial conducted, [exclusively] in China,” Jinjing Liu, from the department of rheumatology at Peking Union Medical College Hospital in Beijing, China, said in an interview.
Ms. Liu presented the results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, during the Abstract Plenary, which highlights the best-scored abstracts of the meeting.
“We are working our best to provide more choices for Chinese patients,” Ms. Liu said, which includes lowering the financial cost of treatments. A locally developed JAK inhibitor could potentially be a much cheaper option than other alternatives that are currently available, she said.
But it is more than that, Ms. Liu said. “The selectivity of SHR0302 for JAK 1 is nine times greater than for JAK 2, so it surpasses either tofacitinib or baricitinib.” The theory is that this higher selectivity for JAK 1 over JAK 2 could lead to fewer adverse events (AEs).
“Maybe it will result in lower JAK 2–associated hematologic side effects,” Ms. Liu said.
“We have noticed that, throughout the clinical trial, the most commonly reported AEs in the drug groups were upper extremity infection [21.7%-22.8% vs 13.8% for placebo] and hyperlipidemia [12.2%-15.3% vs 5.3%].” And for the control group, she said that anemia was the second highest reported AE, at 11.7% vs 6.3% and 7.4% for SHR0302 4 and 8 mg, respectively.
Standard Design
The trial design was typical for a phase 3 study: Multicenter, randomized, placebo controlled, and double blind for the first 24 weeks, followed by an extension period out to 52 weeks. For inclusion in the study, patients had to be aged 18-75 years and have active rheumatoid arthritis and an inadequate response to previous treatment with conventional synthetic disease-modifying antirheumatic drugs.
Of 1085 patients who were initially screened, 566 were randomly allocated to receive placebo (n = 188), SHR0302 4 mg (n = 189), or SHR0302 8 mg (n = 189). The average age of patients was 51 years, and 13.3% of patients were older than 65 years.
Additional Results
Alongside improvements in ACR responses, Ms Liu reported that a significantly higher proportion of patients treated with SHR0302 vs placebo achieved a Disease Activity Score in 28 joints based on C-reactive protein less than 2.6 (29.6% with 4 mg and 39.2% with 8 mg vs 4.2% with placebo; both P < .0001) and at least 3.2 (57.1% and 46.0% vs 15.4%; both P < .0001) at 24 weeks.
There were also greater improvements seen in Health Assessment Questionnaire-Disability Index, 36-item Short-Form (SF36) physical component summary, and SF36 mental component summary scores for active vs placebo treatment.
As for AEs, there were no surprises. During the main 24-week trial period, 81.5%, 90.5%, and 79.3% of patients treated with SHR0302 4 and 8 mg and placebo, respectively, experienced any AE.
Infection-related treatment-emergent adverse effects occurred slightly more often in the SHR0302-treated groups (40.2% for 4 mg and 40.7% for 8 mg) than in the placebo group (34.0%). There was a single case of serious infection that required treatment in the SHR0302 8 mg–treated group but no cases of systemic opportunistic infection.
There was one thromboembolic event and one major cardiovascular event in the 24-week period, both occurring in patients treated with SHR0302 8 mg. There were also single cases of each reported during the extension phase of the trial, but both were in the placebo arm.
Two cases of liver function abnormality — one each in the SHR0302 4- and 8-mg groups — were recorded during the main part of the trial and two cases — both in the SHR0302 4-mg group — during the extension phase.
As for malignancy, there was a single, newly diagnosed case in the SHR0302 4 mg group in the first part of the trial and two cases, both in the SHR0302 4-mg group, during the extension phase.
“We hope this [JAK inhibitor] will be for everybody. But, you know, if it’s for patients, globally, more clinical trials would be required,” Ms. Liu said in an interview. The future, she added, was to start accumulating some real-world data and perhaps do a trial comparing SHR0302 with another JAK inhibitor or a tumor necrosis factor inhibitor.
Another JAK in the Box?
Following her presentation, Ms. Liu at EULAR 2024 was quizzed as to why there were so many screening failures. She responded that she did not have the full data to answer the question but noted that some patients in her center had been worried about being randomized to a placebo. This trial has also been conducted during the COVID-19 pandemic, so that may have been a contributing factor with patients unable to get to their follow-up appointments.
Iain B. McInnes, MD, PhD, vice principal, professor of rheumatology, and head of the College of Medical, Veterinary & Life Sciences at the University of Glasgow, Glasgow, Scotland, commented on the study, saying: “The JAK field is in evolution. We need to understand the broader toxicities. There is an unexplained mechanism driving potential cardiovascular and malignant risk in a small proportion of patients receiving the drugs.”
Dr. McInnes added, “It’s really unclear whether the solution is going to be greater selectivity and potency, or whether we need to think really about selecting the right patients for a JAK inhibitor.”
The study was funded by Jiangsu Hengrui Pharmaceuticals. Two of the 18 authors of the abstract were employees of the sponsoring company, but Ms. Liu reported having no conflicts of interest. Dr. McInnes reported serving on speaker’s bureaus for AbbVie and UCB; receiving consulting fees received from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Eli Lilly, Evelo, Gilead, Janssen, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB; and receiving grant/research support from GlaxoSmithKline, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, and UCB.
A version of this article appeared on Medscape.com.
VIENNA — The highly selective oral Janus kinase (JAK) inhibitor SHR0302 (ivarmacitinib) enables more patients with active rheumatoid arthritis to meet American College of Rheumatology (ACR) response criteria than placebo, the results of a phase 3 trial showed.
After 24 weeks of daily treatment, the primary endpoint of an ACR20 response was met by 40.4% of those who had been given placebo, 70.4% who had received a 4-mg dose, and 75.1% given an 8-mg dose. At the same time point, ACR50 responses were a respective 15.4%, 46.0%, and 57.1%, and ACR70 responses were 6.9%, 22.2%, and 31.7%. All analyses comparing SHR0302 vs placebo were highly significant (P < .0001).
First Phase 3 Trial in China
“This is the first highly selective JAK inhibitor originally developed, and a phase 3 clinical trial conducted, [exclusively] in China,” Jinjing Liu, from the department of rheumatology at Peking Union Medical College Hospital in Beijing, China, said in an interview.
Ms. Liu presented the results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, during the Abstract Plenary, which highlights the best-scored abstracts of the meeting.
“We are working our best to provide more choices for Chinese patients,” Ms. Liu said, which includes lowering the financial cost of treatments. A locally developed JAK inhibitor could potentially be a much cheaper option than other alternatives that are currently available, she said.
But it is more than that, Ms. Liu said. “The selectivity of SHR0302 for JAK 1 is nine times greater than for JAK 2, so it surpasses either tofacitinib or baricitinib.” The theory is that this higher selectivity for JAK 1 over JAK 2 could lead to fewer adverse events (AEs).
“Maybe it will result in lower JAK 2–associated hematologic side effects,” Ms. Liu said.
“We have noticed that, throughout the clinical trial, the most commonly reported AEs in the drug groups were upper extremity infection [21.7%-22.8% vs 13.8% for placebo] and hyperlipidemia [12.2%-15.3% vs 5.3%].” And for the control group, she said that anemia was the second highest reported AE, at 11.7% vs 6.3% and 7.4% for SHR0302 4 and 8 mg, respectively.
Standard Design
The trial design was typical for a phase 3 study: Multicenter, randomized, placebo controlled, and double blind for the first 24 weeks, followed by an extension period out to 52 weeks. For inclusion in the study, patients had to be aged 18-75 years and have active rheumatoid arthritis and an inadequate response to previous treatment with conventional synthetic disease-modifying antirheumatic drugs.
Of 1085 patients who were initially screened, 566 were randomly allocated to receive placebo (n = 188), SHR0302 4 mg (n = 189), or SHR0302 8 mg (n = 189). The average age of patients was 51 years, and 13.3% of patients were older than 65 years.
Additional Results
Alongside improvements in ACR responses, Ms Liu reported that a significantly higher proportion of patients treated with SHR0302 vs placebo achieved a Disease Activity Score in 28 joints based on C-reactive protein less than 2.6 (29.6% with 4 mg and 39.2% with 8 mg vs 4.2% with placebo; both P < .0001) and at least 3.2 (57.1% and 46.0% vs 15.4%; both P < .0001) at 24 weeks.
There were also greater improvements seen in Health Assessment Questionnaire-Disability Index, 36-item Short-Form (SF36) physical component summary, and SF36 mental component summary scores for active vs placebo treatment.
As for AEs, there were no surprises. During the main 24-week trial period, 81.5%, 90.5%, and 79.3% of patients treated with SHR0302 4 and 8 mg and placebo, respectively, experienced any AE.
Infection-related treatment-emergent adverse effects occurred slightly more often in the SHR0302-treated groups (40.2% for 4 mg and 40.7% for 8 mg) than in the placebo group (34.0%). There was a single case of serious infection that required treatment in the SHR0302 8 mg–treated group but no cases of systemic opportunistic infection.
There was one thromboembolic event and one major cardiovascular event in the 24-week period, both occurring in patients treated with SHR0302 8 mg. There were also single cases of each reported during the extension phase of the trial, but both were in the placebo arm.
Two cases of liver function abnormality — one each in the SHR0302 4- and 8-mg groups — were recorded during the main part of the trial and two cases — both in the SHR0302 4-mg group — during the extension phase.
As for malignancy, there was a single, newly diagnosed case in the SHR0302 4 mg group in the first part of the trial and two cases, both in the SHR0302 4-mg group, during the extension phase.
“We hope this [JAK inhibitor] will be for everybody. But, you know, if it’s for patients, globally, more clinical trials would be required,” Ms. Liu said in an interview. The future, she added, was to start accumulating some real-world data and perhaps do a trial comparing SHR0302 with another JAK inhibitor or a tumor necrosis factor inhibitor.
Another JAK in the Box?
Following her presentation, Ms. Liu at EULAR 2024 was quizzed as to why there were so many screening failures. She responded that she did not have the full data to answer the question but noted that some patients in her center had been worried about being randomized to a placebo. This trial has also been conducted during the COVID-19 pandemic, so that may have been a contributing factor with patients unable to get to their follow-up appointments.
Iain B. McInnes, MD, PhD, vice principal, professor of rheumatology, and head of the College of Medical, Veterinary & Life Sciences at the University of Glasgow, Glasgow, Scotland, commented on the study, saying: “The JAK field is in evolution. We need to understand the broader toxicities. There is an unexplained mechanism driving potential cardiovascular and malignant risk in a small proportion of patients receiving the drugs.”
Dr. McInnes added, “It’s really unclear whether the solution is going to be greater selectivity and potency, or whether we need to think really about selecting the right patients for a JAK inhibitor.”
The study was funded by Jiangsu Hengrui Pharmaceuticals. Two of the 18 authors of the abstract were employees of the sponsoring company, but Ms. Liu reported having no conflicts of interest. Dr. McInnes reported serving on speaker’s bureaus for AbbVie and UCB; receiving consulting fees received from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Eli Lilly, Evelo, Gilead, Janssen, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB; and receiving grant/research support from GlaxoSmithKline, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, and UCB.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>VIENNA — The highly selective oral Janus kinase (JAK) inhibitor SHR0302 (ivarmacitinib) enables more patients with active rheumatoid arthritis to meet American </metaDescription> <articlePDF/> <teaserImage>301945</teaserImage> <teaser>SHR0302 (ivarmacitinib) is highly selective for JAK 1 and the first JAK inhibitor to be originally developed and now tested in a phase 3 RA clinical trial exclusively in China.</teaser> <title>Selective JAK 1 Inhibitor for RA Proves Promising in Phase 3 Trial</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">289</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012a43.jpg</altRep> <description role="drol:caption">Jinjing Liu</description> <description role="drol:credit">Sara Freeman/Medscape Medical News</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2400e231.jpg</altRep> <description role="drol:caption">Dr. Iain B. McInnes</description> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Selective JAK 1 Inhibitor for RA Proves Promising in Phase 3 Trial</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">VIENNA</span> — The highly selective oral Janus kinase (JAK) inhibitor SHR0302 (ivarmacitinib) enables more patients with active <span class="Hyperlink">rheumatoid arthritis</span> to meet American College of Rheumatology (ACR) response criteria than placebo, the results of a phase 3 trial showed.</p> <p>After 24 weeks of daily treatment, the primary endpoint of an ACR20 response was met by 40.4% of those who had been given placebo, 70.4% who had received a 4-mg dose, and 75.1% given an 8-mg dose. At the same time point, ACR50 responses were a respective 15.4%, 46.0%, and 57.1%, and ACR70 responses were 6.9%, 22.2%, and 31.7%. All analyses comparing SHR0302 vs placebo were highly significant (<em>P</em> < .0001).<br/><br/></p> <h2>First Phase 3 Trial in China</h2> <p>“This is the first highly selective JAK inhibitor originally developed, and a phase 3 clinical trial conducted, [exclusively] in China,” Jinjing Liu, from the department of rheumatology at <span class="Hyperlink"><a href="https://www.pumch.cn/en.html">Peking Union Medical College Hospital</a></span> in Beijing, China, said in an interview.</p> <p>[[{"fid":"301945","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Jinjing Liu, of the Department of Rheumatology at Peking Union Medical College Hospital in Beijing, China","field_file_image_credit[und][0][value]":"Sara Freeman/Medscape Medical News","field_file_image_caption[und][0][value]":"Jinjing Liu"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]Ms. Liu presented <span class="Hyperlink"><a href="https://ard.bmj.com/content/83/Suppl_1/3">the results</a></span> at the <span class="Hyperlink">European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting</span>, during the Abstract Plenary, which highlights the best-scored abstracts of the meeting.<br/><br/>“We are working our best to provide more choices for Chinese patients,” Ms. Liu said, which includes lowering the financial cost of treatments. A locally developed JAK inhibitor could potentially be a much cheaper option than other alternatives that are currently available, she said.<br/><br/>But it is more than that, Ms. Liu said. “The selectivity of SHR0302 for JAK 1 is nine times greater than for JAK 2, so it surpasses either <span class="Hyperlink">tofacitinib</span> or <span class="Hyperlink">baricitinib</span>.” The theory is that this higher selectivity for JAK 1 over JAK 2 could lead to fewer adverse events (AEs).<br/><br/>“Maybe it will result in lower JAK 2–associated hematologic side effects,” Ms. Liu said.<br/><br/>“We have noticed that, throughout the clinical trial, the most commonly reported AEs in the drug groups were upper extremity infection [21.7%-22.8% vs 13.8% for placebo] and hyperlipidemia [12.2%-15.3% vs 5.3%].” And for the control group, she said that <span class="Hyperlink">anemia</span> was the second highest reported AE, at 11.7% vs 6.3% and 7.4% for SHR0302 4 and 8 mg, respectively.<br/><br/></p> <h2>Standard Design</h2> <p>The trial design was typical for a <span class="Hyperlink"><a href="https://www.clinicaltrials.gov/study/NCT04333771">phase 3 study</a></span>: Multicenter, randomized, placebo controlled, and double blind for the first 24 weeks, followed by an extension period out to 52 weeks. For inclusion in the study, patients had to be aged 18-75 years and have active rheumatoid arthritis and an inadequate response to previous treatment with conventional synthetic disease-modifying antirheumatic drugs.</p> <p>Of 1085 patients who were initially screened, 566 were randomly allocated to receive placebo (n = 188), SHR0302 4 mg (n = 189), or SHR0302 8 mg (n = 189). The average age of patients was 51 years, and 13.3% of patients were older than 65 years.<br/><br/></p> <h2>Additional Results</h2> <p>Alongside improvements in ACR responses, Ms Liu reported that a significantly higher proportion of patients treated with SHR0302 vs placebo achieved a Disease Activity Score in 28 joints based on C-reactive protein less than 2.6 (29.6% with 4 mg and 39.2% with 8 mg vs 4.2% with placebo; both <em>P</em> < .0001) and at least 3.2 (57.1% and 46.0% vs 15.4%; both <em>P</em> < .0001) at 24 weeks.</p> <p>There were also greater improvements seen in Health Assessment Questionnaire-Disability Index, 36-item Short-Form (SF36) physical component summary, and SF36 mental component summary scores for active vs placebo treatment.<br/><br/>As for AEs, there were no surprises. During the main 24-week trial period, 81.5%, 90.5%, and 79.3% of patients treated with SHR0302 4 and 8 mg and placebo, respectively, experienced any AE.<br/><br/>Infection-related treatment-emergent adverse effects occurred slightly more often in the SHR0302-treated groups (40.2% for 4 mg and 40.7% for 8 mg) than in the placebo group (34.0%). There was a single case of serious infection that required treatment in the SHR0302 8 mg–treated group but no cases of systemic opportunistic infection.<br/><br/>There was one thromboembolic event and one major cardiovascular event in the 24-week period, both occurring in patients treated with SHR0302 8 mg. There were also single cases of each reported during the extension phase of the trial, but both were in the placebo arm.<br/><br/>Two cases of liver function abnormality — one each in the SHR0302 4- and 8-mg groups — were recorded during the main part of the trial and two cases — both in the SHR0302 4-mg group — during the extension phase.<br/><br/>As for malignancy, there was a single, newly diagnosed case in the SHR0302 4 mg group in the first part of the trial and two cases, both in the SHR0302 4-mg group, during the extension phase.<br/><br/>“We hope this [JAK inhibitor] will be for everybody. But, you know, if it’s for patients, globally, more clinical trials would be required,” Ms. Liu said in an interview. The future, she added, was to start accumulating some real-world data and perhaps do a trial comparing SHR0302 with another JAK inhibitor or a tumor necrosis factor inhibitor.<br/><br/></p> <h2>Another JAK in the Box?</h2> <p>Following her presentation, Ms. Liu at EULAR 2024 was quizzed as to why there were so many screening failures. She responded that she did not have the full data to answer the question but noted that some patients in her center had been worried about being randomized to a placebo. This trial has also been conducted during the COVID-19 pandemic, so that may have been a contributing factor with patients unable to get to their follow-up appointments.</p> <p>[[{"fid":"262789","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Iain B. McInnes","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Iain B. McInnes"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]Iain B. McInnes, MD, PhD, vice principal, professor of rheumatology, and head of the College of Medical, Veterinary & Life Sciences at the University of Glasgow, Glasgow, Scotland, commented on the study, saying: “The JAK field is in evolution. We need to understand the broader toxicities. There is an unexplained mechanism driving potential cardiovascular and malignant risk in a small proportion of patients receiving the drugs.”<br/><br/>Dr. McInnes added, “It’s really unclear whether the solution is going to be greater selectivity and potency, or whether we need to think really about selecting the right patients for a JAK inhibitor.”<br/><br/>The study was funded by Jiangsu Hengrui Pharmaceuticals. Two of the 18 authors of the abstract were employees of the sponsoring company, but Ms. Liu reported having no conflicts of interest. Dr. McInnes reported serving on speaker’s bureaus for AbbVie and UCB; receiving consulting fees received from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Eli Lilly, Evelo, Gilead, Janssen, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB; and receiving grant/research support from GlaxoSmithKline, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, and UCB.<span class="end"/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/new-jak-1-inhibitor-proves-promising-phase-3-ra-trial-2024a1000bdi">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM EULAR 2024
Upadacitinib Proves Successful in First JAK Inhibitor Trial for Giant Cell Arteritis
VIENNA — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remission in people with new-onset or relapsing giant cell arteritis (GCA).
The primary endpoint of sustained remission — the absence of GCA signs or symptoms from weeks 12 to 52 together with adherence to a steroid-tapering regimen — occurred in 46% of 210 individuals randomly assigned to treatment treated with a once-daily 15-mg dose of upadacitinib and 29% of 105 randomly assigned to placebo (P = .0019).
Nine of the 11 secondary endpoints were also positive for upadacitinib 15 mg vs placebo, and no new safety concerns were identified in a late-breaking abstract presented at the at the annual European Congress of Rheumatology.
First JAK Trial in GCA
This is the first trial to look at the use of a JAK inhibitor for the treatment of GCA, and it is addressing a real unmet need, the presenting study investigator Daniel Blockmans, MD, PhD, of University Hospitals Leuven in Belgium, told this news organization.
Glucocorticoids remain the mainstay of treatment, and tocilizumab has been licensed for use, but people don’t always get better or can relapse, he explained.
“I have the impression that these only suppress the disease but do not cure it,” Dr. Blockmans said, adding that “patients get very well soon after these treatments are started, but there are more and more reports that there is a kind of smoldering vasculitis that exists, and this can lead to dilatation of the aorta.”
Upadacitinib inhibits two JAK-dependent cytokines, interleukin 6 and interferon gamma, which have been implicated in the pathogenesis of GCA. The latter could be particularly important, Dr. Blockmans suggested.
Study Details
SELECT-GCA is an ongoing multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib vs placebo in patients with GCA.
A total of 428 patients have been included: 210 were randomly allocated to treatment with upadacitinib 15 mg, 105 to upadacitinib 7.5 mg, and 105 to placebo. The inclusion of the lower “minimally effective” upadacitinib dose was a requirement of the regulatory authorities, Dr. Blockmans said; the licensed dose in rheumatoid arthritis (RA) is 15 mg.
Dr. Blockmans reported data from the first 52 weeks of the trial during which all patients underwent glucocorticoid tapering — 26 weeks for upadacitinib and 52 weeks for placebo.
No imaging was done in this trial, which Dr. Blockmans said should be considered for future studies.
Secondary Endpoints
One of the key secondary endpoints was sustained complete remission, defined as sustained remission plus a normalized erythrocyte sedimentation rate to ≤ 30 mm/h and reducing high-sensitivity C-reactive protein to < 1 mg/dL.
Sustained complete remission occurred in 37% and 16% of patients treated with upadacitinib 15 mg and placebo, respectively (P < .0001).
Additionally, a significantly lower proportion of upadacitinib 15 mg- than placebo-treated patients experienced at least one disease flare through week 52 (34% vs 56%, P = .0014).
Other positive secondary endpoints for upadacitinib 15 mg vs placebo out to week 52 were the number of disease flares per patient, cumulative glucocorticoid exposure, and complete remission (also at week 24).
And significant changes in SF-36 and FACIT-Fatigue from baseline to week 52 were seen for upadacitinib 15 mg.
The only secondary endpoints not showing a clear benefit for upadacitinib 15 mg were the changes in the Treatment Satisfaction Questionnaire for Medication at 52 weeks and the rate of glucocorticoid-related adverse events through week 52.
As for the 7.5-mg dose of upadacitinib, neither the primary nor secondary endpoints were significantly better vs placebo.
‘Life-Changing’
The study’s findings could be “really life-changing” for patients with this type of vasculitis if upadacitinib gets approval for use in this indication, Milena Bond, MD, PhD, of Brunico Hospital in Italy, told this news organization at the meeting.
“Unfortunately, nowadays, we still have only a few options for treating these patients,” she said. “So, this drug could be really, really important.”
Dr. Bond added: “The data ... also shows there is a very good safety profile, which was a main concern given the class of the drug. So, I’m very positive about this treatment and very excited to see the preliminary results.”
After his presentation, Dr. Blockmans said, “Of course, if we already had an ideal treatment for GCA, there would be no need for a JAK inhibitor, but I don’t think that steroid treatment or tocilizumab treatment is the ideal treatment.”
Judicious Use Still Warranted
Upadacitinib still needs to be used cautiously, following appropriate guidance from the European Medicines Agency (EMA) and the US Food and Drug Administration.
Dr. Bond said: “It is not advised to use to the drug when people are older than 65 years old,” according to the EMA, for example, and “given the rules that we have, I would not use this drug as a first-line treatment. We do not do that for rheumatoid arthritis.”
But, she added, “As for arthritis, when you fail treating patients with the other alternatives, you could use this drug, and you have to discuss risks with the patients.”
Dr. Blockmans reported there had been no increased risk for major adverse cardiovascular events or venous thromboembolism associated with upadacitinib relative to placebo in the population of patients studied, and he pointed out that they had a much higher risk for these events than perhaps an RA population.
He said: “It’s effective, and it’s apparently safe in these older people, despite what we heard about tofacitinib in the ORAL [Surveillance] study; we didn’t see these problems here in this elderly population.”
The SELECT-GCA trial was funded by AbbVie, and the company participated in all aspects of the study, including its design, conduct, interpretation of data, and reporting. Dr. Blockmans received no funding or other honoraria from the company but reported a research grant from Roche and consulting fees from GlaxoSmithKline. Most of his coauthors reported financial relationships with AbbVie, and some are employees of the company. Dr. Bond reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
VIENNA — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remission in people with new-onset or relapsing giant cell arteritis (GCA).
The primary endpoint of sustained remission — the absence of GCA signs or symptoms from weeks 12 to 52 together with adherence to a steroid-tapering regimen — occurred in 46% of 210 individuals randomly assigned to treatment treated with a once-daily 15-mg dose of upadacitinib and 29% of 105 randomly assigned to placebo (P = .0019).
Nine of the 11 secondary endpoints were also positive for upadacitinib 15 mg vs placebo, and no new safety concerns were identified in a late-breaking abstract presented at the at the annual European Congress of Rheumatology.
First JAK Trial in GCA
This is the first trial to look at the use of a JAK inhibitor for the treatment of GCA, and it is addressing a real unmet need, the presenting study investigator Daniel Blockmans, MD, PhD, of University Hospitals Leuven in Belgium, told this news organization.
Glucocorticoids remain the mainstay of treatment, and tocilizumab has been licensed for use, but people don’t always get better or can relapse, he explained.
“I have the impression that these only suppress the disease but do not cure it,” Dr. Blockmans said, adding that “patients get very well soon after these treatments are started, but there are more and more reports that there is a kind of smoldering vasculitis that exists, and this can lead to dilatation of the aorta.”
Upadacitinib inhibits two JAK-dependent cytokines, interleukin 6 and interferon gamma, which have been implicated in the pathogenesis of GCA. The latter could be particularly important, Dr. Blockmans suggested.
Study Details
SELECT-GCA is an ongoing multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib vs placebo in patients with GCA.
A total of 428 patients have been included: 210 were randomly allocated to treatment with upadacitinib 15 mg, 105 to upadacitinib 7.5 mg, and 105 to placebo. The inclusion of the lower “minimally effective” upadacitinib dose was a requirement of the regulatory authorities, Dr. Blockmans said; the licensed dose in rheumatoid arthritis (RA) is 15 mg.
Dr. Blockmans reported data from the first 52 weeks of the trial during which all patients underwent glucocorticoid tapering — 26 weeks for upadacitinib and 52 weeks for placebo.
No imaging was done in this trial, which Dr. Blockmans said should be considered for future studies.
Secondary Endpoints
One of the key secondary endpoints was sustained complete remission, defined as sustained remission plus a normalized erythrocyte sedimentation rate to ≤ 30 mm/h and reducing high-sensitivity C-reactive protein to < 1 mg/dL.
Sustained complete remission occurred in 37% and 16% of patients treated with upadacitinib 15 mg and placebo, respectively (P < .0001).
Additionally, a significantly lower proportion of upadacitinib 15 mg- than placebo-treated patients experienced at least one disease flare through week 52 (34% vs 56%, P = .0014).
Other positive secondary endpoints for upadacitinib 15 mg vs placebo out to week 52 were the number of disease flares per patient, cumulative glucocorticoid exposure, and complete remission (also at week 24).
And significant changes in SF-36 and FACIT-Fatigue from baseline to week 52 were seen for upadacitinib 15 mg.
The only secondary endpoints not showing a clear benefit for upadacitinib 15 mg were the changes in the Treatment Satisfaction Questionnaire for Medication at 52 weeks and the rate of glucocorticoid-related adverse events through week 52.
As for the 7.5-mg dose of upadacitinib, neither the primary nor secondary endpoints were significantly better vs placebo.
‘Life-Changing’
The study’s findings could be “really life-changing” for patients with this type of vasculitis if upadacitinib gets approval for use in this indication, Milena Bond, MD, PhD, of Brunico Hospital in Italy, told this news organization at the meeting.
“Unfortunately, nowadays, we still have only a few options for treating these patients,” she said. “So, this drug could be really, really important.”
Dr. Bond added: “The data ... also shows there is a very good safety profile, which was a main concern given the class of the drug. So, I’m very positive about this treatment and very excited to see the preliminary results.”
After his presentation, Dr. Blockmans said, “Of course, if we already had an ideal treatment for GCA, there would be no need for a JAK inhibitor, but I don’t think that steroid treatment or tocilizumab treatment is the ideal treatment.”
Judicious Use Still Warranted
Upadacitinib still needs to be used cautiously, following appropriate guidance from the European Medicines Agency (EMA) and the US Food and Drug Administration.
Dr. Bond said: “It is not advised to use to the drug when people are older than 65 years old,” according to the EMA, for example, and “given the rules that we have, I would not use this drug as a first-line treatment. We do not do that for rheumatoid arthritis.”
But, she added, “As for arthritis, when you fail treating patients with the other alternatives, you could use this drug, and you have to discuss risks with the patients.”
Dr. Blockmans reported there had been no increased risk for major adverse cardiovascular events or venous thromboembolism associated with upadacitinib relative to placebo in the population of patients studied, and he pointed out that they had a much higher risk for these events than perhaps an RA population.
He said: “It’s effective, and it’s apparently safe in these older people, despite what we heard about tofacitinib in the ORAL [Surveillance] study; we didn’t see these problems here in this elderly population.”
The SELECT-GCA trial was funded by AbbVie, and the company participated in all aspects of the study, including its design, conduct, interpretation of data, and reporting. Dr. Blockmans received no funding or other honoraria from the company but reported a research grant from Roche and consulting fees from GlaxoSmithKline. Most of his coauthors reported financial relationships with AbbVie, and some are employees of the company. Dr. Bond reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
VIENNA — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remission in people with new-onset or relapsing giant cell arteritis (GCA).
The primary endpoint of sustained remission — the absence of GCA signs or symptoms from weeks 12 to 52 together with adherence to a steroid-tapering regimen — occurred in 46% of 210 individuals randomly assigned to treatment treated with a once-daily 15-mg dose of upadacitinib and 29% of 105 randomly assigned to placebo (P = .0019).
Nine of the 11 secondary endpoints were also positive for upadacitinib 15 mg vs placebo, and no new safety concerns were identified in a late-breaking abstract presented at the at the annual European Congress of Rheumatology.
First JAK Trial in GCA
This is the first trial to look at the use of a JAK inhibitor for the treatment of GCA, and it is addressing a real unmet need, the presenting study investigator Daniel Blockmans, MD, PhD, of University Hospitals Leuven in Belgium, told this news organization.
Glucocorticoids remain the mainstay of treatment, and tocilizumab has been licensed for use, but people don’t always get better or can relapse, he explained.
“I have the impression that these only suppress the disease but do not cure it,” Dr. Blockmans said, adding that “patients get very well soon after these treatments are started, but there are more and more reports that there is a kind of smoldering vasculitis that exists, and this can lead to dilatation of the aorta.”
Upadacitinib inhibits two JAK-dependent cytokines, interleukin 6 and interferon gamma, which have been implicated in the pathogenesis of GCA. The latter could be particularly important, Dr. Blockmans suggested.
Study Details
SELECT-GCA is an ongoing multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib vs placebo in patients with GCA.
A total of 428 patients have been included: 210 were randomly allocated to treatment with upadacitinib 15 mg, 105 to upadacitinib 7.5 mg, and 105 to placebo. The inclusion of the lower “minimally effective” upadacitinib dose was a requirement of the regulatory authorities, Dr. Blockmans said; the licensed dose in rheumatoid arthritis (RA) is 15 mg.
Dr. Blockmans reported data from the first 52 weeks of the trial during which all patients underwent glucocorticoid tapering — 26 weeks for upadacitinib and 52 weeks for placebo.
No imaging was done in this trial, which Dr. Blockmans said should be considered for future studies.
Secondary Endpoints
One of the key secondary endpoints was sustained complete remission, defined as sustained remission plus a normalized erythrocyte sedimentation rate to ≤ 30 mm/h and reducing high-sensitivity C-reactive protein to < 1 mg/dL.
Sustained complete remission occurred in 37% and 16% of patients treated with upadacitinib 15 mg and placebo, respectively (P < .0001).
Additionally, a significantly lower proportion of upadacitinib 15 mg- than placebo-treated patients experienced at least one disease flare through week 52 (34% vs 56%, P = .0014).
Other positive secondary endpoints for upadacitinib 15 mg vs placebo out to week 52 were the number of disease flares per patient, cumulative glucocorticoid exposure, and complete remission (also at week 24).
And significant changes in SF-36 and FACIT-Fatigue from baseline to week 52 were seen for upadacitinib 15 mg.
The only secondary endpoints not showing a clear benefit for upadacitinib 15 mg were the changes in the Treatment Satisfaction Questionnaire for Medication at 52 weeks and the rate of glucocorticoid-related adverse events through week 52.
As for the 7.5-mg dose of upadacitinib, neither the primary nor secondary endpoints were significantly better vs placebo.
‘Life-Changing’
The study’s findings could be “really life-changing” for patients with this type of vasculitis if upadacitinib gets approval for use in this indication, Milena Bond, MD, PhD, of Brunico Hospital in Italy, told this news organization at the meeting.
“Unfortunately, nowadays, we still have only a few options for treating these patients,” she said. “So, this drug could be really, really important.”
Dr. Bond added: “The data ... also shows there is a very good safety profile, which was a main concern given the class of the drug. So, I’m very positive about this treatment and very excited to see the preliminary results.”
After his presentation, Dr. Blockmans said, “Of course, if we already had an ideal treatment for GCA, there would be no need for a JAK inhibitor, but I don’t think that steroid treatment or tocilizumab treatment is the ideal treatment.”
Judicious Use Still Warranted
Upadacitinib still needs to be used cautiously, following appropriate guidance from the European Medicines Agency (EMA) and the US Food and Drug Administration.
Dr. Bond said: “It is not advised to use to the drug when people are older than 65 years old,” according to the EMA, for example, and “given the rules that we have, I would not use this drug as a first-line treatment. We do not do that for rheumatoid arthritis.”
But, she added, “As for arthritis, when you fail treating patients with the other alternatives, you could use this drug, and you have to discuss risks with the patients.”
Dr. Blockmans reported there had been no increased risk for major adverse cardiovascular events or venous thromboembolism associated with upadacitinib relative to placebo in the population of patients studied, and he pointed out that they had a much higher risk for these events than perhaps an RA population.
He said: “It’s effective, and it’s apparently safe in these older people, despite what we heard about tofacitinib in the ORAL [Surveillance] study; we didn’t see these problems here in this elderly population.”
The SELECT-GCA trial was funded by AbbVie, and the company participated in all aspects of the study, including its design, conduct, interpretation of data, and reporting. Dr. Blockmans received no funding or other honoraria from the company but reported a research grant from Roche and consulting fees from GlaxoSmithKline. Most of his coauthors reported financial relationships with AbbVie, and some are employees of the company. Dr. Bond reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>VIENNA — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remissio</metaDescription> <articlePDF/> <teaserImage/> <teaser>Results from the SELECT-GCA study showed that upadacitinib (Rinvoq) induced significant and sustained remission in people with new-onset or relapsing giant cell arteritis.</teaser> <title>Upadacitinib Proves Successful in First JAK Inhibitor Trial for Giant Cell Arteritis</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>nr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle>Neurology Reviews</journalTitle> <journalFullTitle>Neurology Reviews</journalFullTitle> <copyrightStatement>2018 Frontline Medical Communications Inc.,</copyrightStatement> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>22</term> <term>21</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">241</term> <term>285</term> <term>290</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Upadacitinib Proves Successful in First JAK Inhibitor Trial for Giant Cell Arteritis</title> <deck/> </itemMeta> <itemContent> <p>VIENNA — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remission in people with new-onset or relapsing giant cell arteritis (GCA).</p> <p>The primary endpoint of sustained remission — the absence of GCA signs or symptoms from weeks 12 to 52 together with adherence to a steroid-tapering regimen — occurred in 46% of 210 individuals randomly assigned to treatment treated with a once-daily 15-mg dose of upadacitinib and 29% of 105 randomly assigned to placebo (P = .0019).<br/><br/>Nine of the 11 secondary endpoints were also positive for upadacitinib 15 mg vs placebo, and no new safety concerns were identified in a <a href="https://ard.bmj.com/content/83/Suppl_1/232">late-breaking abstract</a> presented at the at the annual European Congress of Rheumatology.<br/><br/></p> <h2>First JAK Trial in GCA</h2> <p>This is the first trial to look at the use of a JAK inhibitor for the treatment of GCA, and it is addressing a real unmet need, the presenting study investigator <a href="https://www.uzleuven.be/en/physicians-and-specialists/daniel-blockmans">Daniel Blockmans</a>, MD, PhD, of University Hospitals Leuven in Belgium, told this news organization.</p> <p>Glucocorticoids remain the mainstay of treatment, and tocilizumab has been licensed for use, but people don’t always get better or can relapse, he explained.<br/><br/>“I have the impression that these only suppress the disease but do not cure it,” Dr. Blockmans said, adding that “patients get very well soon after these treatments are started, but there are more and more reports that there is a kind of smoldering vasculitis that exists, and this can lead to dilatation of the aorta.”<br/><br/>Upadacitinib inhibits two JAK-dependent cytokines, interleukin 6 and interferon gamma, which have been implicated in the pathogenesis of GCA. The latter could be particularly important, Dr. Blockmans suggested.<br/><br/></p> <h2>Study Details</h2> <p><a href="https://classic.clinicaltrials.gov/ct2/show/NCT03725202">SELECT-GCA</a> is an ongoing multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib vs placebo in patients with GCA.</p> <p>A total of 428 patients have been included: 210 were randomly allocated to treatment with upadacitinib 15 mg, 105 to upadacitinib 7.5 mg, and 105 to placebo. The inclusion of the lower “minimally effective” upadacitinib dose was a requirement of the regulatory authorities, Dr. Blockmans said; the licensed dose in rheumatoid arthritis (RA) is 15 mg.<br/><br/>Dr. Blockmans reported data from the first 52 weeks of the trial during which all patients underwent glucocorticoid tapering — 26 weeks for upadacitinib and 52 weeks for placebo.<br/><br/>No imaging was done in this trial, which Dr. Blockmans said should be considered for future studies.<br/><br/></p> <h2>Secondary Endpoints</h2> <p>One of the key secondary endpoints was sustained complete remission, defined as sustained remission plus a normalized erythrocyte sedimentation rate to ≤ 30 mm/h and reducing high-sensitivity C-reactive protein to < 1 mg/dL.</p> <p>Sustained complete remission occurred in 37% and 16% of patients treated with upadacitinib 15 mg and placebo, respectively (<em>P</em> < .0001).<br/><br/>Additionally, a significantly lower proportion of upadacitinib 15 mg- than placebo-treated patients experienced at least one disease flare through week 52 (34% vs 56%, <em>P</em> = .0014).<br/><br/>Other positive secondary endpoints for upadacitinib 15 mg vs placebo out to week 52 were the number of disease flares per patient, cumulative glucocorticoid exposure, and complete remission (also at week 24).<br/><br/>And significant changes in SF-36 and FACIT-Fatigue from baseline to week 52 were seen for upadacitinib 15 mg.<br/><br/>The only secondary endpoints not showing a clear benefit for upadacitinib 15 mg were the changes in the Treatment Satisfaction Questionnaire for Medication at 52 weeks and the rate of glucocorticoid-related adverse events through week 52.<br/><br/>As for the 7.5-mg dose of upadacitinib, neither the primary nor secondary endpoints were significantly better vs placebo.<br/><br/></p> <h2>‘Life-Changing’</h2> <p>The study’s findings could be “really life-changing” for patients with this type of vasculitis if upadacitinib gets approval for use in this indication, Milena Bond, MD, PhD, of Brunico Hospital in Italy, told this news organization at the meeting.</p> <p>“Unfortunately, nowadays, we still have only a few options for treating these patients,” she said. “So, this drug could be really, really important.”<br/><br/>Dr. Bond added: “The data ... also shows there is a very good safety profile, which was a main concern given the class of the drug. So, I’m very positive about this treatment and very excited to see the preliminary results.”<br/><br/>After his presentation, Dr. Blockmans said, “Of course, if we already had an ideal treatment for GCA, there would be no need for a JAK inhibitor, but I don’t think that steroid treatment or tocilizumab treatment is the ideal treatment.”<br/><br/></p> <h2>Judicious Use Still Warranted</h2> <p>Upadacitinib still needs to be used cautiously, following appropriate guidance from the European Medicines Agency (EMA) and the US Food and Drug Administration.</p> <p>Dr. Bond said: “It is not advised to use to the drug when people are older than 65 years old,” according to the EMA, for example, and “given the rules that we have, I would not use this drug as a first-line treatment. We do not do that for rheumatoid arthritis.”<br/><br/>But, she added, “As for arthritis, when you fail treating patients with the other alternatives, you could use this drug, and you have to discuss risks with the patients.”<br/><br/>Dr. Blockmans reported there had been no increased risk for major adverse cardiovascular events or venous thromboembolism associated with upadacitinib relative to placebo in the population of patients studied, and he pointed out that they had a much higher risk for these events than perhaps an RA population.<br/><br/>He said: “It’s effective, and it’s apparently safe in these older people, despite what we heard about tofacitinib in the <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2109927">ORAL [Surveillance] study</a>; we didn’t see these problems here in this elderly population.”<br/><br/>The SELECT-GCA trial was funded by AbbVie, and the company participated in all aspects of the study, including its design, conduct, interpretation of data, and reporting. Dr. Blockmans received no funding or other honoraria from the company but reported a research grant from Roche and consulting fees from GlaxoSmithKline. Most of his coauthors reported financial relationships with AbbVie, and some are employees of the company. Dr. Bond reported no relevant financial relationships.</p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/upadacitinib-improves-giant-cell-arteritis-phase-3-trial-2024a1000b4r">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM EULAR 2024
EULAR 2024 Preview: Therapeutics in Development Take Center Stage
The European Alliance of Associations for Rheumatology (EULAR) 2024 European Congress of Rheumatology annual meeting is about to take place in Vienna, Austria. From June 12 to 15, some of the world’s leading researchers and clinicians will convene to present and learn about data on some of the new and innovative treatments for people with rheumatic and musculoskeletal diseases (RMDs) as well as to discuss how to use and optimize existing approaches.
Ahead of the Congress, this news organization asked the Congress Committee’s Scientific Programme Chair Caroline Ospelt, MD, PhD, and Abstract Chair Christian Dejaco, MD, PhD, MBA, to discuss some of their highlights of this year’s meeting.
From Bench to Bedside
“For me, the beauty at EULAR is really that you have the latest on basic research, how this can be translated in clinical trials, and then the last step would be how EULAR recommends it to be used in clinical practice,” Dr. Ospelt, professor of experimental rheumatology at University Hospital Zurich, said in an interview.
“So, if you go to EULAR continuously, you can actually follow the whole story of how novelty comes into clinical practice,” she added.
In a separate interview, Dr. Dejaco, a consultant rheumatologist and associate professor at the Medical University of Graz in Austria, said: “There are several new drug trials that are going to be presented.”
One of his highlights on the use of new drugs for the treatment of giant cell arteritis will be the phase 3 SELECT-GCA trial of the Janus kinase (JAK) inhibitor upadacitinib (LBA0001).
“It’s a trial that hopefully will lead to the approval of this drug in this indication,” Dr. Dejaco said.
Late-Breaking Abstracts
Dr. Ospelt noted: “We had a lot of good late-breaking abstracts this year.”
Some of these include:
- Real-world data on the comparative effectiveness of five different classes of drugs used to treat psoriatic arthritis (PsA; LBA0002)
- The 16-week results of a phase 2b/3 study with the novel interleukin (IL)–17A inhibitor izokibep in people with PsA (LBA0005)
- Data from the COSPIRIT-JIA trial on the efficacy and safety of ixekizumab (Taltz) in juvenile idiopathic arthritis (LBA0009)
- Phase 2 data on the safety and efficacy of the CD38-targeting monoclonal antibody daratumumab in systemic lupus erythematosus (LBA0007)
- Results of the phase 2 DAHLIAS study of the anti–neonatal Fc receptor monoclonal antibody nipocalimab in people with primary Sjögren disease (LBA0010)
- Safety and immunogenicity data from a phase 1 study of an active anti–IL-6 immunotherapy in people with knee osteoarthritis (LBA0011)
The latter is “really interesting,” Dr. Ospelt said. As of now, there is no approved treatment for osteoarthritis, and there is no immunotherapy, “so this would be the first.”
But it’s not just the late-breaker abstracts to look out for. Dr. Dejaco highlighted two abstracts that will be presented during the Abstract Plenary:
- A phase 3 study of a new selective JAK1 inhibitor, SHR0302, in rheumatoid arthritis (OP0037)
- A multi-omics analysis and targeted gene-editing study in people with , which causes inflammatory and hematologic changes (OP0073)
Of the latter, he said, “this disease is still incompletely understood, and this abstract really helps to better understand the mechanisms underlying this disease.”
One to Watch: CAR T-Cell Therapy
Dr. Ospelt said that the scientific program is about 80% clinical and 20% basic science overall. However, more sessions are being held jointly because data are starting to move from the bench to bedside.
One of the basic science areas that has had “a real buzz” around it and is now producing results in the clinic is the use of chimeric antigen receptor (CAR) T cells. In one of the first, and perhaps aptly titled What Is New, or WIN, sessions of the congress, Georg Schett, MD, vice president of research at Friedrich-Alexander-Universität Erlangen-Nüremberg in Germany, will discuss the use of CAR T-cell therapy for inflammatory RMDs. There are also multiple abstract presentations on this topic.
In-depth tissue analysis and prediction of treatment response is another interesting approach, Dr. Ospelt said. “I think that’s the way to go, that we come from the blood, we go into the tissue.” A “very nice” example of this approach will be presented during the Abstract Plenary session on Wednesday, June 12, looking at how synovial tissue macrophages may be able to give information on likely treatment response in treatment-naive rheumatoid arthritis (OP0062). There are also some further findings related to the tissue biopsy–driven treatment trial R4RA that are being presented at the meeting (OP0218, OP0242, and POS0351).
EULAR Highlighted Sessions
Among the highlighted sessions on the EULAR 2024 website is one on axial involvement in PsA and spondyloarthritis (SpA).
“Axial involvement in psoriatic arthritis and peripheral involvement in axial spondyloarthritis is quite a hot topic at the moment,” Dr. Ospelt said. There are lots of questions: “How connected are they? How different are they? Do we need different treatment for axial involvement compared to peripheral involvement?”
Another EULAR highlighted session is the 75th anniversary of glucocorticoid treatment, during which Past President of EULAR and Emeritus Professor of Rheumatology Josef S. Smolen, MD, will overview the “past, present, and future” of glucocorticoids in RMDs. Consultant rheumatologist Frank Buttgereit, MD, from the German Rheumatism Research Center in Berlin, will discuss the practicalities of using these drugs in clinical practice.
Dr. Dejaco noted: “Glucocorticoids have been one of the most important treatments for a very long time, and they’re still the most important treatment for the acute treatment of systemic inflammatory diseases.”
For a long time, there was no alternative to using steroids, he added, but steroid-sparing options now exist, and there will be data presented on a new type of drug that could potentially be used to control cortisol levels in the body (OP0335).
Recommendations and More
Dr. Ospelt and Dr. Dejaco both pointed out other sessions that are likely to be very popular, such as the first and second EULAR Recommendations sessions, a session on rheumatoid arthritis prevention, as well as the many presentations and sessions on digital health and nonpharmacologic interventions such as exercise.
With over 5242 submitted abstracts, there is going to be no shortage of data being presented at EULAR 2024. Alongside the traditional abstract submission categories, this year there is a new clinical case reports category.
“We had about 578 submissions for that category,” Dr. Dejaco said. There were 3315 abstracts submitted for the clinical research category, 812 for the basic and translational research category, 283 from health professionals in rheumatology, 152 from patient groups, and 102 in the field of pediatric rheumatology.
Join in On-Site, Watch on Demand
EULAR 2024 reverts to an on-site–only meeting this year. Some of the more lighthearted yet educational elements of the program for those attending include the second edition of the EMEUNET Rheumatology Quiz and, new for this year, two escape rooms. These rooms will provide an interactive experience where small teams will have to solve rheumatologic conundrums in order to escape the room within the hour, Dr. Dejaco explained. There will also be a morning run on Friday, June 14. “It’s not a race, it’s simply to meet and run together,” Dr. Dejaco said.
But if you cannot make the congress in person, the EULAR 2024 Livestream will be broadcasting throughout the congress. Anyone registered by June 30 will have on-demand access to the recorded content from June 17 until December 31, 2024.
Abstracts for the meeting will be published as a supplement to Annals of the Rheumatic Diseases, the official journal of EULAR.
Dr. Ospelt reported no relevant financial relationships. Dr. Dejaco has received consulting/speaker fees from AbbVie, Eli Lilly, Janssen, Sparrow, Novartis, Pfizer, Roche, Galapagos, and Sanofi.
A version of this article appeared on Medscape.com.
The European Alliance of Associations for Rheumatology (EULAR) 2024 European Congress of Rheumatology annual meeting is about to take place in Vienna, Austria. From June 12 to 15, some of the world’s leading researchers and clinicians will convene to present and learn about data on some of the new and innovative treatments for people with rheumatic and musculoskeletal diseases (RMDs) as well as to discuss how to use and optimize existing approaches.
Ahead of the Congress, this news organization asked the Congress Committee’s Scientific Programme Chair Caroline Ospelt, MD, PhD, and Abstract Chair Christian Dejaco, MD, PhD, MBA, to discuss some of their highlights of this year’s meeting.
From Bench to Bedside
“For me, the beauty at EULAR is really that you have the latest on basic research, how this can be translated in clinical trials, and then the last step would be how EULAR recommends it to be used in clinical practice,” Dr. Ospelt, professor of experimental rheumatology at University Hospital Zurich, said in an interview.
“So, if you go to EULAR continuously, you can actually follow the whole story of how novelty comes into clinical practice,” she added.
In a separate interview, Dr. Dejaco, a consultant rheumatologist and associate professor at the Medical University of Graz in Austria, said: “There are several new drug trials that are going to be presented.”
One of his highlights on the use of new drugs for the treatment of giant cell arteritis will be the phase 3 SELECT-GCA trial of the Janus kinase (JAK) inhibitor upadacitinib (LBA0001).
“It’s a trial that hopefully will lead to the approval of this drug in this indication,” Dr. Dejaco said.
Late-Breaking Abstracts
Dr. Ospelt noted: “We had a lot of good late-breaking abstracts this year.”
Some of these include:
- Real-world data on the comparative effectiveness of five different classes of drugs used to treat psoriatic arthritis (PsA; LBA0002)
- The 16-week results of a phase 2b/3 study with the novel interleukin (IL)–17A inhibitor izokibep in people with PsA (LBA0005)
- Data from the COSPIRIT-JIA trial on the efficacy and safety of ixekizumab (Taltz) in juvenile idiopathic arthritis (LBA0009)
- Phase 2 data on the safety and efficacy of the CD38-targeting monoclonal antibody daratumumab in systemic lupus erythematosus (LBA0007)
- Results of the phase 2 DAHLIAS study of the anti–neonatal Fc receptor monoclonal antibody nipocalimab in people with primary Sjögren disease (LBA0010)
- Safety and immunogenicity data from a phase 1 study of an active anti–IL-6 immunotherapy in people with knee osteoarthritis (LBA0011)
The latter is “really interesting,” Dr. Ospelt said. As of now, there is no approved treatment for osteoarthritis, and there is no immunotherapy, “so this would be the first.”
But it’s not just the late-breaker abstracts to look out for. Dr. Dejaco highlighted two abstracts that will be presented during the Abstract Plenary:
- A phase 3 study of a new selective JAK1 inhibitor, SHR0302, in rheumatoid arthritis (OP0037)
- A multi-omics analysis and targeted gene-editing study in people with , which causes inflammatory and hematologic changes (OP0073)
Of the latter, he said, “this disease is still incompletely understood, and this abstract really helps to better understand the mechanisms underlying this disease.”
One to Watch: CAR T-Cell Therapy
Dr. Ospelt said that the scientific program is about 80% clinical and 20% basic science overall. However, more sessions are being held jointly because data are starting to move from the bench to bedside.
One of the basic science areas that has had “a real buzz” around it and is now producing results in the clinic is the use of chimeric antigen receptor (CAR) T cells. In one of the first, and perhaps aptly titled What Is New, or WIN, sessions of the congress, Georg Schett, MD, vice president of research at Friedrich-Alexander-Universität Erlangen-Nüremberg in Germany, will discuss the use of CAR T-cell therapy for inflammatory RMDs. There are also multiple abstract presentations on this topic.
In-depth tissue analysis and prediction of treatment response is another interesting approach, Dr. Ospelt said. “I think that’s the way to go, that we come from the blood, we go into the tissue.” A “very nice” example of this approach will be presented during the Abstract Plenary session on Wednesday, June 12, looking at how synovial tissue macrophages may be able to give information on likely treatment response in treatment-naive rheumatoid arthritis (OP0062). There are also some further findings related to the tissue biopsy–driven treatment trial R4RA that are being presented at the meeting (OP0218, OP0242, and POS0351).
EULAR Highlighted Sessions
Among the highlighted sessions on the EULAR 2024 website is one on axial involvement in PsA and spondyloarthritis (SpA).
“Axial involvement in psoriatic arthritis and peripheral involvement in axial spondyloarthritis is quite a hot topic at the moment,” Dr. Ospelt said. There are lots of questions: “How connected are they? How different are they? Do we need different treatment for axial involvement compared to peripheral involvement?”
Another EULAR highlighted session is the 75th anniversary of glucocorticoid treatment, during which Past President of EULAR and Emeritus Professor of Rheumatology Josef S. Smolen, MD, will overview the “past, present, and future” of glucocorticoids in RMDs. Consultant rheumatologist Frank Buttgereit, MD, from the German Rheumatism Research Center in Berlin, will discuss the practicalities of using these drugs in clinical practice.
Dr. Dejaco noted: “Glucocorticoids have been one of the most important treatments for a very long time, and they’re still the most important treatment for the acute treatment of systemic inflammatory diseases.”
For a long time, there was no alternative to using steroids, he added, but steroid-sparing options now exist, and there will be data presented on a new type of drug that could potentially be used to control cortisol levels in the body (OP0335).
Recommendations and More
Dr. Ospelt and Dr. Dejaco both pointed out other sessions that are likely to be very popular, such as the first and second EULAR Recommendations sessions, a session on rheumatoid arthritis prevention, as well as the many presentations and sessions on digital health and nonpharmacologic interventions such as exercise.
With over 5242 submitted abstracts, there is going to be no shortage of data being presented at EULAR 2024. Alongside the traditional abstract submission categories, this year there is a new clinical case reports category.
“We had about 578 submissions for that category,” Dr. Dejaco said. There were 3315 abstracts submitted for the clinical research category, 812 for the basic and translational research category, 283 from health professionals in rheumatology, 152 from patient groups, and 102 in the field of pediatric rheumatology.
Join in On-Site, Watch on Demand
EULAR 2024 reverts to an on-site–only meeting this year. Some of the more lighthearted yet educational elements of the program for those attending include the second edition of the EMEUNET Rheumatology Quiz and, new for this year, two escape rooms. These rooms will provide an interactive experience where small teams will have to solve rheumatologic conundrums in order to escape the room within the hour, Dr. Dejaco explained. There will also be a morning run on Friday, June 14. “It’s not a race, it’s simply to meet and run together,” Dr. Dejaco said.
But if you cannot make the congress in person, the EULAR 2024 Livestream will be broadcasting throughout the congress. Anyone registered by June 30 will have on-demand access to the recorded content from June 17 until December 31, 2024.
Abstracts for the meeting will be published as a supplement to Annals of the Rheumatic Diseases, the official journal of EULAR.
Dr. Ospelt reported no relevant financial relationships. Dr. Dejaco has received consulting/speaker fees from AbbVie, Eli Lilly, Janssen, Sparrow, Novartis, Pfizer, Roche, Galapagos, and Sanofi.
A version of this article appeared on Medscape.com.
The European Alliance of Associations for Rheumatology (EULAR) 2024 European Congress of Rheumatology annual meeting is about to take place in Vienna, Austria. From June 12 to 15, some of the world’s leading researchers and clinicians will convene to present and learn about data on some of the new and innovative treatments for people with rheumatic and musculoskeletal diseases (RMDs) as well as to discuss how to use and optimize existing approaches.
Ahead of the Congress, this news organization asked the Congress Committee’s Scientific Programme Chair Caroline Ospelt, MD, PhD, and Abstract Chair Christian Dejaco, MD, PhD, MBA, to discuss some of their highlights of this year’s meeting.
From Bench to Bedside
“For me, the beauty at EULAR is really that you have the latest on basic research, how this can be translated in clinical trials, and then the last step would be how EULAR recommends it to be used in clinical practice,” Dr. Ospelt, professor of experimental rheumatology at University Hospital Zurich, said in an interview.
“So, if you go to EULAR continuously, you can actually follow the whole story of how novelty comes into clinical practice,” she added.
In a separate interview, Dr. Dejaco, a consultant rheumatologist and associate professor at the Medical University of Graz in Austria, said: “There are several new drug trials that are going to be presented.”
One of his highlights on the use of new drugs for the treatment of giant cell arteritis will be the phase 3 SELECT-GCA trial of the Janus kinase (JAK) inhibitor upadacitinib (LBA0001).
“It’s a trial that hopefully will lead to the approval of this drug in this indication,” Dr. Dejaco said.
Late-Breaking Abstracts
Dr. Ospelt noted: “We had a lot of good late-breaking abstracts this year.”
Some of these include:
- Real-world data on the comparative effectiveness of five different classes of drugs used to treat psoriatic arthritis (PsA; LBA0002)
- The 16-week results of a phase 2b/3 study with the novel interleukin (IL)–17A inhibitor izokibep in people with PsA (LBA0005)
- Data from the COSPIRIT-JIA trial on the efficacy and safety of ixekizumab (Taltz) in juvenile idiopathic arthritis (LBA0009)
- Phase 2 data on the safety and efficacy of the CD38-targeting monoclonal antibody daratumumab in systemic lupus erythematosus (LBA0007)
- Results of the phase 2 DAHLIAS study of the anti–neonatal Fc receptor monoclonal antibody nipocalimab in people with primary Sjögren disease (LBA0010)
- Safety and immunogenicity data from a phase 1 study of an active anti–IL-6 immunotherapy in people with knee osteoarthritis (LBA0011)
The latter is “really interesting,” Dr. Ospelt said. As of now, there is no approved treatment for osteoarthritis, and there is no immunotherapy, “so this would be the first.”
But it’s not just the late-breaker abstracts to look out for. Dr. Dejaco highlighted two abstracts that will be presented during the Abstract Plenary:
- A phase 3 study of a new selective JAK1 inhibitor, SHR0302, in rheumatoid arthritis (OP0037)
- A multi-omics analysis and targeted gene-editing study in people with , which causes inflammatory and hematologic changes (OP0073)
Of the latter, he said, “this disease is still incompletely understood, and this abstract really helps to better understand the mechanisms underlying this disease.”
One to Watch: CAR T-Cell Therapy
Dr. Ospelt said that the scientific program is about 80% clinical and 20% basic science overall. However, more sessions are being held jointly because data are starting to move from the bench to bedside.
One of the basic science areas that has had “a real buzz” around it and is now producing results in the clinic is the use of chimeric antigen receptor (CAR) T cells. In one of the first, and perhaps aptly titled What Is New, or WIN, sessions of the congress, Georg Schett, MD, vice president of research at Friedrich-Alexander-Universität Erlangen-Nüremberg in Germany, will discuss the use of CAR T-cell therapy for inflammatory RMDs. There are also multiple abstract presentations on this topic.
In-depth tissue analysis and prediction of treatment response is another interesting approach, Dr. Ospelt said. “I think that’s the way to go, that we come from the blood, we go into the tissue.” A “very nice” example of this approach will be presented during the Abstract Plenary session on Wednesday, June 12, looking at how synovial tissue macrophages may be able to give information on likely treatment response in treatment-naive rheumatoid arthritis (OP0062). There are also some further findings related to the tissue biopsy–driven treatment trial R4RA that are being presented at the meeting (OP0218, OP0242, and POS0351).
EULAR Highlighted Sessions
Among the highlighted sessions on the EULAR 2024 website is one on axial involvement in PsA and spondyloarthritis (SpA).
“Axial involvement in psoriatic arthritis and peripheral involvement in axial spondyloarthritis is quite a hot topic at the moment,” Dr. Ospelt said. There are lots of questions: “How connected are they? How different are they? Do we need different treatment for axial involvement compared to peripheral involvement?”
Another EULAR highlighted session is the 75th anniversary of glucocorticoid treatment, during which Past President of EULAR and Emeritus Professor of Rheumatology Josef S. Smolen, MD, will overview the “past, present, and future” of glucocorticoids in RMDs. Consultant rheumatologist Frank Buttgereit, MD, from the German Rheumatism Research Center in Berlin, will discuss the practicalities of using these drugs in clinical practice.
Dr. Dejaco noted: “Glucocorticoids have been one of the most important treatments for a very long time, and they’re still the most important treatment for the acute treatment of systemic inflammatory diseases.”
For a long time, there was no alternative to using steroids, he added, but steroid-sparing options now exist, and there will be data presented on a new type of drug that could potentially be used to control cortisol levels in the body (OP0335).
Recommendations and More
Dr. Ospelt and Dr. Dejaco both pointed out other sessions that are likely to be very popular, such as the first and second EULAR Recommendations sessions, a session on rheumatoid arthritis prevention, as well as the many presentations and sessions on digital health and nonpharmacologic interventions such as exercise.
With over 5242 submitted abstracts, there is going to be no shortage of data being presented at EULAR 2024. Alongside the traditional abstract submission categories, this year there is a new clinical case reports category.
“We had about 578 submissions for that category,” Dr. Dejaco said. There were 3315 abstracts submitted for the clinical research category, 812 for the basic and translational research category, 283 from health professionals in rheumatology, 152 from patient groups, and 102 in the field of pediatric rheumatology.
Join in On-Site, Watch on Demand
EULAR 2024 reverts to an on-site–only meeting this year. Some of the more lighthearted yet educational elements of the program for those attending include the second edition of the EMEUNET Rheumatology Quiz and, new for this year, two escape rooms. These rooms will provide an interactive experience where small teams will have to solve rheumatologic conundrums in order to escape the room within the hour, Dr. Dejaco explained. There will also be a morning run on Friday, June 14. “It’s not a race, it’s simply to meet and run together,” Dr. Dejaco said.
But if you cannot make the congress in person, the EULAR 2024 Livestream will be broadcasting throughout the congress. Anyone registered by June 30 will have on-demand access to the recorded content from June 17 until December 31, 2024.
Abstracts for the meeting will be published as a supplement to Annals of the Rheumatic Diseases, the official journal of EULAR.
Dr. Ospelt reported no relevant financial relationships. Dr. Dejaco has received consulting/speaker fees from AbbVie, Eli Lilly, Janssen, Sparrow, Novartis, Pfizer, Roche, Galapagos, and Sanofi.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>The European Alliance of Associations for Rheumatology (EULAR) 2024 European Congress of Rheumatology annual meeting is about to take place in Vienna, Austria. </metaDescription> <articlePDF/> <teaserImage>301894</teaserImage> <teaser>Experts give their top picks and hot tips on data being presented at the upcoming European Congress of Rheumatology taking place on June 12-15 in Vienna, Austria.</teaser> <title>EULAR 2024 Preview: Therapeutics in Development Take Center Stage</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>21</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">289</term> <term>282</term> <term>271</term> <term>265</term> <term>241</term> <term>290</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/240129f3.jpg</altRep> <description role="drol:caption">Dr. Caroline Ospelt</description> <description role="drol:credit">University Hospital Zurich</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/240129f4.jpg</altRep> <description role="drol:caption">Dr. Christian Dejaco</description> <description role="drol:credit">EULAR</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>EULAR 2024 Preview: Therapeutics in Development Take Center Stage</title> <deck/> </itemMeta> <itemContent> <p>The European Alliance of Associations for Rheumatology (EULAR) 2024 European Congress of Rheumatology annual meeting is about to take place in Vienna, Austria. From June 12 to 15, some of the world’s leading researchers and clinicians will convene to present and learn about data on some of the new and innovative treatments for people with rheumatic and musculoskeletal diseases (RMDs) as well as to discuss how to use and optimize existing approaches. </p> <p>Ahead of the Congress, this news organization asked the Congress Committee’s Scientific Programme Chair <a href="https://www.cabmm.uzh.ch/en/Membership2/MemberApplFields/MolMed/CarolineOspelt.html">Caroline Ospelt</a>, MD, PhD, and Abstract Chair <a href="https://forschung.medunigraz.at/fodok/suchen.person_uebersicht?sprache_in=en&menue_id_in=101&id_in=80374">Christian Dejaco</a>, MD, PhD, MBA, to discuss some of their highlights of this year’s meeting.<br/><br/></p> <h2>From Bench to Bedside</h2> <p>“For me, the beauty at EULAR is really that you have the latest on basic research, how this can be translated in clinical trials, and then the last step would be how EULAR recommends it to be used in clinical practice,” Dr. Ospelt, professor of experimental rheumatology at University Hospital Zurich, said in an interview. [[{"fid":"301894","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Caroline Ospelt, professor of experimental rheumatology at University Hospital Zurich in Switzerland","field_file_image_credit[und][0][value]":"University Hospital Zurich","field_file_image_caption[und][0][value]":"Dr. Caroline Ospelt"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]</p> <p>“So, if you go to EULAR continuously, you can actually follow the whole story of how novelty comes into clinical practice,” she added. <br/><br/>In a separate interview, Dr. Dejaco, a consultant rheumatologist and associate professor at the Medical University of Graz in Austria, said: “There are several new drug trials that are going to be presented.” <br/><br/>One of his highlights on the use of new drugs for the treatment of <span class="Hyperlink">giant cell arteritis</span> will be the phase 3 SELECT-GCA trial of the Janus kinase (JAK) inhibitor <span class="Hyperlink">upadacitinib</span> (<span class="Hyperlink"><a href="https://apps-congress.eular.org/eular2024/en-GB/pag/presentation/18972">LBA0001</a></span>).<br/><br/>“It’s a trial that hopefully will lead to the approval of this drug in this indication,” Dr. Dejaco said.[[{"fid":"301895","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Christian Dejaco, a consultant rheumatologist and associate professor at the Medical University of Graz in Austria","field_file_image_credit[und][0][value]":"EULAR","field_file_image_caption[und][0][value]":"Dr. Christian Dejaco"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]<br/><br/></p> <h2>Late-Breaking Abstracts</h2> <p>Dr. Ospelt noted: “We had a lot of good late-breaking abstracts this year.” </p> <p>Some of these include: </p> <ul class="body"> <li>Real-world data on the comparative effectiveness of five different classes of drugs used to treat psoriatic arthritis (PsA; ) </li> <li>The 16-week results of a phase 2b/3 study with the novel interleukin (IL)–17A inhibitor izokibep in people with PsA ()</li> <li>Data from the COSPIRIT-JIA trial on the efficacy and safety of ixekizumab (Taltz) in juvenile idiopathic arthritis ()</li> <li>Phase 2 data on the safety and efficacy of the CD38-targeting monoclonal antibody daratumumab in systemic lupus erythematosus ()</li> <li>Results of the phase 2 DAHLIAS study of the anti–neonatal Fc receptor monoclonal antibody nipocalimab in people with primary Sjögren disease () </li> <li>Safety and immunogenicity data from a phase 1 study of an active anti–IL-6 immunotherapy in people with knee osteoarthritis ()</li> </ul> <p>The latter is “really interesting,” Dr. Ospelt said. As of now, there is no approved treatment for osteoarthritis, and there is no immunotherapy, “so this would be the first.” <br/><br/>But it’s not just the late-breaker abstracts to look out for. Dr. Dejaco highlighted two abstracts that will be presented during the <a href="https://apps-congress.eular.org/eular2024/en-GB/pag/session/2110">Abstract Plenary</a>: </p> <ul class="body"> <li>A phase 3 study of a new selective JAK1 inhibitor, SHR0302, in rheumatoid arthritis ()</li> <li>A multi-omics analysis and targeted gene-editing study in people with , which causes inflammatory and hematologic changes ()</li> </ul> <p>Of the latter, he said, “this disease is still incompletely understood, and this abstract really helps to better understand the mechanisms underlying this disease.”<br/><br/></p> <h2>One to Watch: CAR T-Cell Therapy </h2> <p>Dr. Ospelt said that the scientific program is about 80% clinical and 20% basic science overall. However, more sessions are being held jointly because data are starting to move from the bench to bedside. </p> <p>One of the basic science areas that has had “a real buzz” around it and is now producing results in the clinic is the use of chimeric antigen receptor (CAR) T cells. In one of the first, and perhaps aptly titled What Is New, or WIN, sessions of the congress, <a href="https://www.fau.eu/fau/organisation-and-committees/executive-board/prof-dr-georg-schett/">Georg Schett</a>, MD, vice president of research at Friedrich-Alexander-Universität Erlangen-Nüremberg in Germany, will discuss the use of <a href="https://apps-congress.eular.org/eular2024/en-GB/pag/session/1907">CAR T-cell therapy for inflammatory RMDs</a>. There are also multiple abstract presentations on this topic. <br/><br/>In-depth tissue analysis and prediction of treatment response is another interesting approach, Dr. Ospelt said. “I think that’s the way to go, that we come from the blood, we go into the tissue.” A “very nice” example of this approach will be presented during the <a href="https://apps-congress.eular.org/eular2024/en-GB/pag/session/2110">Abstract Plenary</a> session on Wednesday, June 12, looking at how synovial tissue macrophages may be able to give information on likely treatment response in treatment-naive rheumatoid arthritis (<a href="https://apps-congress.eular.org/eular2024/en-GB/pag/presentation/17036">OP0062</a>). There are also some further findings related to the tissue biopsy–driven treatment trial <a href="https://r4ra-nihr.whri.qmul.ac.uk/">R4RA</a> that are being presented at the meeting (<a href="https://apps-congress.eular.org/eular2024/en-GB/pag/presentation/17592">OP0218</a>, <a href="https://apps-congress.eular.org/eular2024/en-GB/pag/presentation/17716">OP0242</a>, and <a href="https://apps-congress.eular.org/eular2024/en-GB/pag/presentation/17228">POS0351</a>).<br/><br/></p> <h2>EULAR Highlighted Sessions</h2> <p>Among the <a href="https://congress.eular.org/highlighted_sessions.cfm">highlighted sessions</a> on the EULAR 2024 website is one <a href="https://apps-congress.eular.org/eular2024/en-GB/pag/session/1905">on axial involvement in PsA and spondyloarthritis</a> (SpA). </p> <p>“Axial involvement in psoriatic arthritis and peripheral involvement in axial spondyloarthritis is quite a hot topic at the moment,” Dr. Ospelt said. There are lots of questions: “How connected are they? How different are they? Do we need different treatment for axial involvement compared to peripheral involvement?” <br/><br/>Another EULAR highlighted session is the <a href="https://apps-congress.eular.org/eular2024/en-GB/pag/session/2047">75th anniversary of glucocorticoid treatment</a>, during which Past President of EULAR and Emeritus Professor of Rheumatology <a href="https://en.wikipedia.org/wiki/Josef_Smolen">Josef S. Smolen</a>, MD, will overview the “past, present, and future” of glucocorticoids in RMDs. Consultant rheumatologist <a href="https://www.drfz.de/en/uber-uns/koepfe/prof-dr-med-frank-buttgereit/">Frank Buttgereit</a>, MD, from the German Rheumatism Research Center in Berlin, will discuss the practicalities of using these drugs in clinical practice.<br/><br/>Dr. Dejaco noted: “Glucocorticoids have been one of the most important treatments for a very long time, and they’re still the most important treatment for the acute treatment of systemic inflammatory diseases.”<br/><br/>For a long time, there was no alternative to using steroids, he added, but steroid-sparing options now exist, and there will be data presented on a new type of drug that could potentially be used to control cortisol levels in the body (<a href="https://apps-congress.eular.org/eular2024/en-GB/pag/presentation/17072">OP0335</a>).<br/><br/></p> <h2>Recommendations and More</h2> <p>Dr. Ospelt and Dr. Dejaco both pointed out other sessions that are likely to be very popular, such as the <a href="https://apps-congress.eular.org/eular2024/en-GB/pag/session/2049">first</a> and <a href="https://apps-congress.eular.org/eular2024/en-GB/pag/session/1920">second</a> EULAR Recommendations sessions, a session on <a href="https://apps-congress.eular.org/eular2024/en-GB/pag/session/1981">rheumatoid arthritis prevention</a>, as well as the many presentations and sessions on <a href="https://apps-congress.eular.org/eular2024/en-GB/pag/session/1914">digital health</a> and nonpharmacologic interventions such as <a href="https://apps-congress.eular.org/eular2024/en-GB/pag/session/2217">exercise</a>. </p> <p>With over 5242 submitted abstracts, there is going to be no shortage of data being presented at EULAR 2024. Alongside the traditional abstract submission categories, this year there is a new clinical case reports category. <br/><br/>“We had about 578 submissions for that category,” Dr. Dejaco said. There were 3315 abstracts submitted for the clinical research category, 812 for the basic and translational research category, 283 from health professionals in rheumatology, 152 from patient groups, and 102 in the field of pediatric rheumatology.<br/><br/></p> <h2>Join in On-Site, Watch on Demand </h2> <p>EULAR 2024 reverts to an on-site–only meeting this year. Some of the more lighthearted yet educational elements of the program for those attending include the second edition of the <a href="https://apps-congress.eular.org/eular2024/en-GB/pag/session/1999">EMEUNET Rheumatology Quiz</a> and, new for this year, two escape rooms. These rooms will provide an interactive experience where small teams will have to solve rheumatologic conundrums in order to escape the room within the hour, Dr. Dejaco explained. There will also be a <a href="https://forms.office.com/pages/responsepage.aspx?id=6UGD6hSyqkeXP0pI186fJkcVyZ4Y0ilLo0JUl4f4d2pUOFY0VDdOMVhBMUpKVDJTTkZTU0Y5VVk2Vy4u&utm_source=twitter&utm_medium=social&utm_campaign&utm_content=ap_nwxwdkyvbv">morning run</a> on Friday, June 14. “It’s not a race, it’s simply to meet and run together,” Dr. Dejaco said. </p> <p>But if you cannot make the congress in person, the <a href="https://www.youtube.com/watch?v=7GZcsLnfdZI&list=PLrhgQ-ztgkhc6zrSQrVTpY3BzFNvO_N4V&index=1">EULAR 2024 Livestream</a> will be broadcasting throughout the congress. Anyone <a href="https://congress.eular.org/registration.cfm">registered</a> by June 30 will have on-demand access to the recorded content from June 17 until December 31, 2024. <br/><br/>Abstracts for the meeting will be published as a supplement to <em>Annals of the Rheumatic Diseases</em>, the official journal of EULAR. <br/><br/>Dr. Ospelt reported no relevant financial relationships. Dr. Dejaco has received consulting/speaker fees from AbbVie, Eli Lilly, Janssen, Sparrow, Novartis, Pfizer, Roche, Galapagos, and Sanofi.</p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/eular-2024-preview-whats-not-miss-this-years-congress-2024a1000avi">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
What Does Natural Healing of ACL Ruptures Mean for Long-Term Outcomes?
VIENNA — Nearly one third of anterior cruciate ligament (ACL) injuries appear to heal without surgery, according to an analysis of three-dimensional MRI data taken from the NACOX study, presented as a late-breaking poster at the OARSI 2024 World Congress.
At 2 years after injury, three-dimensional MRI showed that 13 of 43 (30%) knees had evidence of normal, continuous ACL fibers. Moreover, a further 14 (33%) knees had a continuous ACL fiber structure following rehabilitation alone. ACL fibers were partly (16%) or completely (21%) ruptured in the remainder of cases.
“If you think of the ACL like a rope, when there is continuity, it means those fibers have rejoined,” study coauthor Stephanie Filbay, PhD, an associate professor at the University of Melbourne in Australia, told this news organization.
“Within that, there’s a few variations of healing that we’re seeing. Some look like they’ve never been injured, while some have rejoined but appear thinner or longer than a normal ACL,” Dr. Filbay said.
She added: “What all this research is showing is that it’s happening at a much higher rate than we thought possible. And in some of the studies, it looks like ACL healing is associated with very favorable outcomes.”
At OARSI 2024, Dr. Filbay presented additional data from her and others’ research on the relationships between ACL healing and long-term functional outcomes and osteoarthritis (OA) incidence in comparisons between patients’ treatment pathways: Early ACL surgery, rehabilitation followed by delayed surgery, or rehabilitation only.
Healing Without Surgery
The idea that the ACL can heal without surgery is relatively recent and perhaps still not widely accepted as a concept, as Dr. Filbay explained during a plenary lecture at the congress.
Dr. Filbay explained that the ideal management of ACL injury depends on the severity of knee injury and whether someone’s knee is stable after trying nonsurgical management. Results of the ACL SNNAP trial, for example, have suggested that surgical reconstruction is superior to a rehabilitation strategy for managing non-acute ACL injuries where there are persistent symptoms of instability.
However, there have been two trials — COMPARE performed in the Netherlands and KANON performed in Sweden — that found that early surgery was no better than a strategy of initial rehabilitation with the option of having a delayed ACL surgery if needed.
What Happens Long Term?
Posttraumatic OA is a well-known long-term consequence of ACL injury. According to a recent meta-analysis, there is a sevenfold increased risk for OA comparing people who have and have not had an ACL injury.
ACL injury also results in OA occurring at an earlier age than in people with OA who have not had an ACL injury. This has been shown to progress at a faster rate and be associated with a longer period of disability, Dr. Filbay said at the congress, sponsored by the Osteoarthritis Research Society International.
But does the ACL really heal? Dr. Filbay thinks that it does and has been involved in several studies that have used MRI to look at how the ACL may do so.
In a recently published paper, Dr. Filbay and colleagues reported the findings from a secondary analysis of the KANON trial and found that nearly one in three (30%) of the participants who had been randomized to optional delayed surgery had MRI evidence of healing at 2 years. But when they excluded people who had delayed surgery, 53% of people managed by rehabilitation alone had evidence of healing.
The evaluation also found that those who had a healed vs non-healed ligament had better results using the Knee Injury and Osteoarthritis Outcome Score (KOOS), and that there were better outcomes at 2 years among those with ACL healing vs those who had early or delayed ACL surgery.
ACL Continuity and Long-Term Outcomes
At OARSI 2024, Dr. Filbay and colleagues reported an even longer-term secondary analysis of the KANON trial on the relationship between ACL healing at 5 years and outcomes at 11 years. The results were first reported in NEJM Evidence.
Dr. Filbay reported that participants with ACL continuity on MRI at 5 years actually had worse patient-reported outcomes 11 years later than those who were managed with early or delayed ACL reconstruction.
“This does not align with previous findings suggesting better 2-year outcomes compared to the surgically managed groups,” Dr. Filbay said.
However, people with ACL continuity following rehabilitation did seem to show numerically similar or fewer signs of radiographic OA at 11 years vs the surgical groups.
Radiographic OA of the tibiofemoral joint (TFJ) or patellofemoral joint (PFJ) at 11 years was observed in a respective 14% and 21% of people with ACL continuity at 5 years (n = 14) and in 22% and 11% of people with ACL discontinuity at 5 years in the rehabilitation alone group.
By comparison, radiographic OA of the TFJ or PFJ at 11 years was seen in a respective 23% and 35% of people who had rehabilitation with delayed surgery (n = 26) and in 18% and 41% of those who had early surgery (n = 49).
These are descriptive results, Dr. Filbay said, because the numbers were too small to do a statistical analysis. Further, larger, longitudinal studies will be needed.
Posttraumatic OA After ACL Surgery
Elsewhere at OARSI 2024, Matthew Harkey, PhD, and colleagues from Michigan State University, East Lansing, Michigan, reported data showing that nearly two thirds of people who undergo surgical reconstruction have symptoms at 6 months that could be indicative of early knee OA.
Knee symptoms indicative of OA declined to 53% at 12 months and 45% at 24 months.
“It’s a bit complex — we can’t outright say arthritis is developing, but there’s a large group of patients whose symptoms linger long after surgery,” Dr. Harkey said in a press release.
“Often, clinicians assume that these postoperative symptoms will naturally improve as patients reengage with their usual activities. However, what we’re seeing suggests these symptoms persist and likely require a targeted approach to manage or improve them,” Dr. Harkey said.
The analysis used data on 3752 individuals aged 14-40 years who were enrolled in the New Zealand ACL Registry and who completed the KOOS at 6, 12, and 24 months after having ACL reconstruction.
Dr. Harkey and team reported that one in three people had persistent early OA symptoms at 2 years, while 23% had no early OA symptoms at any timepoint.
The studies were independently supported. Dr. Filbay and Dr. Harkey had no relevant financial relationships to report.
Dr. Filbay and colleagues have developed a treatment decision aid for individuals who have sustained an ACL injury. This provides information on the different treatment options available and how they compare.
A version of this article appeared on Medscape.com.
VIENNA — Nearly one third of anterior cruciate ligament (ACL) injuries appear to heal without surgery, according to an analysis of three-dimensional MRI data taken from the NACOX study, presented as a late-breaking poster at the OARSI 2024 World Congress.
At 2 years after injury, three-dimensional MRI showed that 13 of 43 (30%) knees had evidence of normal, continuous ACL fibers. Moreover, a further 14 (33%) knees had a continuous ACL fiber structure following rehabilitation alone. ACL fibers were partly (16%) or completely (21%) ruptured in the remainder of cases.
“If you think of the ACL like a rope, when there is continuity, it means those fibers have rejoined,” study coauthor Stephanie Filbay, PhD, an associate professor at the University of Melbourne in Australia, told this news organization.
“Within that, there’s a few variations of healing that we’re seeing. Some look like they’ve never been injured, while some have rejoined but appear thinner or longer than a normal ACL,” Dr. Filbay said.
She added: “What all this research is showing is that it’s happening at a much higher rate than we thought possible. And in some of the studies, it looks like ACL healing is associated with very favorable outcomes.”
At OARSI 2024, Dr. Filbay presented additional data from her and others’ research on the relationships between ACL healing and long-term functional outcomes and osteoarthritis (OA) incidence in comparisons between patients’ treatment pathways: Early ACL surgery, rehabilitation followed by delayed surgery, or rehabilitation only.
Healing Without Surgery
The idea that the ACL can heal without surgery is relatively recent and perhaps still not widely accepted as a concept, as Dr. Filbay explained during a plenary lecture at the congress.
Dr. Filbay explained that the ideal management of ACL injury depends on the severity of knee injury and whether someone’s knee is stable after trying nonsurgical management. Results of the ACL SNNAP trial, for example, have suggested that surgical reconstruction is superior to a rehabilitation strategy for managing non-acute ACL injuries where there are persistent symptoms of instability.
However, there have been two trials — COMPARE performed in the Netherlands and KANON performed in Sweden — that found that early surgery was no better than a strategy of initial rehabilitation with the option of having a delayed ACL surgery if needed.
What Happens Long Term?
Posttraumatic OA is a well-known long-term consequence of ACL injury. According to a recent meta-analysis, there is a sevenfold increased risk for OA comparing people who have and have not had an ACL injury.
ACL injury also results in OA occurring at an earlier age than in people with OA who have not had an ACL injury. This has been shown to progress at a faster rate and be associated with a longer period of disability, Dr. Filbay said at the congress, sponsored by the Osteoarthritis Research Society International.
But does the ACL really heal? Dr. Filbay thinks that it does and has been involved in several studies that have used MRI to look at how the ACL may do so.
In a recently published paper, Dr. Filbay and colleagues reported the findings from a secondary analysis of the KANON trial and found that nearly one in three (30%) of the participants who had been randomized to optional delayed surgery had MRI evidence of healing at 2 years. But when they excluded people who had delayed surgery, 53% of people managed by rehabilitation alone had evidence of healing.
The evaluation also found that those who had a healed vs non-healed ligament had better results using the Knee Injury and Osteoarthritis Outcome Score (KOOS), and that there were better outcomes at 2 years among those with ACL healing vs those who had early or delayed ACL surgery.
ACL Continuity and Long-Term Outcomes
At OARSI 2024, Dr. Filbay and colleagues reported an even longer-term secondary analysis of the KANON trial on the relationship between ACL healing at 5 years and outcomes at 11 years. The results were first reported in NEJM Evidence.
Dr. Filbay reported that participants with ACL continuity on MRI at 5 years actually had worse patient-reported outcomes 11 years later than those who were managed with early or delayed ACL reconstruction.
“This does not align with previous findings suggesting better 2-year outcomes compared to the surgically managed groups,” Dr. Filbay said.
However, people with ACL continuity following rehabilitation did seem to show numerically similar or fewer signs of radiographic OA at 11 years vs the surgical groups.
Radiographic OA of the tibiofemoral joint (TFJ) or patellofemoral joint (PFJ) at 11 years was observed in a respective 14% and 21% of people with ACL continuity at 5 years (n = 14) and in 22% and 11% of people with ACL discontinuity at 5 years in the rehabilitation alone group.
By comparison, radiographic OA of the TFJ or PFJ at 11 years was seen in a respective 23% and 35% of people who had rehabilitation with delayed surgery (n = 26) and in 18% and 41% of those who had early surgery (n = 49).
These are descriptive results, Dr. Filbay said, because the numbers were too small to do a statistical analysis. Further, larger, longitudinal studies will be needed.
Posttraumatic OA After ACL Surgery
Elsewhere at OARSI 2024, Matthew Harkey, PhD, and colleagues from Michigan State University, East Lansing, Michigan, reported data showing that nearly two thirds of people who undergo surgical reconstruction have symptoms at 6 months that could be indicative of early knee OA.
Knee symptoms indicative of OA declined to 53% at 12 months and 45% at 24 months.
“It’s a bit complex — we can’t outright say arthritis is developing, but there’s a large group of patients whose symptoms linger long after surgery,” Dr. Harkey said in a press release.
“Often, clinicians assume that these postoperative symptoms will naturally improve as patients reengage with their usual activities. However, what we’re seeing suggests these symptoms persist and likely require a targeted approach to manage or improve them,” Dr. Harkey said.
The analysis used data on 3752 individuals aged 14-40 years who were enrolled in the New Zealand ACL Registry and who completed the KOOS at 6, 12, and 24 months after having ACL reconstruction.
Dr. Harkey and team reported that one in three people had persistent early OA symptoms at 2 years, while 23% had no early OA symptoms at any timepoint.
The studies were independently supported. Dr. Filbay and Dr. Harkey had no relevant financial relationships to report.
Dr. Filbay and colleagues have developed a treatment decision aid for individuals who have sustained an ACL injury. This provides information on the different treatment options available and how they compare.
A version of this article appeared on Medscape.com.
VIENNA — Nearly one third of anterior cruciate ligament (ACL) injuries appear to heal without surgery, according to an analysis of three-dimensional MRI data taken from the NACOX study, presented as a late-breaking poster at the OARSI 2024 World Congress.
At 2 years after injury, three-dimensional MRI showed that 13 of 43 (30%) knees had evidence of normal, continuous ACL fibers. Moreover, a further 14 (33%) knees had a continuous ACL fiber structure following rehabilitation alone. ACL fibers were partly (16%) or completely (21%) ruptured in the remainder of cases.
“If you think of the ACL like a rope, when there is continuity, it means those fibers have rejoined,” study coauthor Stephanie Filbay, PhD, an associate professor at the University of Melbourne in Australia, told this news organization.
“Within that, there’s a few variations of healing that we’re seeing. Some look like they’ve never been injured, while some have rejoined but appear thinner or longer than a normal ACL,” Dr. Filbay said.
She added: “What all this research is showing is that it’s happening at a much higher rate than we thought possible. And in some of the studies, it looks like ACL healing is associated with very favorable outcomes.”
At OARSI 2024, Dr. Filbay presented additional data from her and others’ research on the relationships between ACL healing and long-term functional outcomes and osteoarthritis (OA) incidence in comparisons between patients’ treatment pathways: Early ACL surgery, rehabilitation followed by delayed surgery, or rehabilitation only.
Healing Without Surgery
The idea that the ACL can heal without surgery is relatively recent and perhaps still not widely accepted as a concept, as Dr. Filbay explained during a plenary lecture at the congress.
Dr. Filbay explained that the ideal management of ACL injury depends on the severity of knee injury and whether someone’s knee is stable after trying nonsurgical management. Results of the ACL SNNAP trial, for example, have suggested that surgical reconstruction is superior to a rehabilitation strategy for managing non-acute ACL injuries where there are persistent symptoms of instability.
However, there have been two trials — COMPARE performed in the Netherlands and KANON performed in Sweden — that found that early surgery was no better than a strategy of initial rehabilitation with the option of having a delayed ACL surgery if needed.
What Happens Long Term?
Posttraumatic OA is a well-known long-term consequence of ACL injury. According to a recent meta-analysis, there is a sevenfold increased risk for OA comparing people who have and have not had an ACL injury.
ACL injury also results in OA occurring at an earlier age than in people with OA who have not had an ACL injury. This has been shown to progress at a faster rate and be associated with a longer period of disability, Dr. Filbay said at the congress, sponsored by the Osteoarthritis Research Society International.
But does the ACL really heal? Dr. Filbay thinks that it does and has been involved in several studies that have used MRI to look at how the ACL may do so.
In a recently published paper, Dr. Filbay and colleagues reported the findings from a secondary analysis of the KANON trial and found that nearly one in three (30%) of the participants who had been randomized to optional delayed surgery had MRI evidence of healing at 2 years. But when they excluded people who had delayed surgery, 53% of people managed by rehabilitation alone had evidence of healing.
The evaluation also found that those who had a healed vs non-healed ligament had better results using the Knee Injury and Osteoarthritis Outcome Score (KOOS), and that there were better outcomes at 2 years among those with ACL healing vs those who had early or delayed ACL surgery.
ACL Continuity and Long-Term Outcomes
At OARSI 2024, Dr. Filbay and colleagues reported an even longer-term secondary analysis of the KANON trial on the relationship between ACL healing at 5 years and outcomes at 11 years. The results were first reported in NEJM Evidence.
Dr. Filbay reported that participants with ACL continuity on MRI at 5 years actually had worse patient-reported outcomes 11 years later than those who were managed with early or delayed ACL reconstruction.
“This does not align with previous findings suggesting better 2-year outcomes compared to the surgically managed groups,” Dr. Filbay said.
However, people with ACL continuity following rehabilitation did seem to show numerically similar or fewer signs of radiographic OA at 11 years vs the surgical groups.
Radiographic OA of the tibiofemoral joint (TFJ) or patellofemoral joint (PFJ) at 11 years was observed in a respective 14% and 21% of people with ACL continuity at 5 years (n = 14) and in 22% and 11% of people with ACL discontinuity at 5 years in the rehabilitation alone group.
By comparison, radiographic OA of the TFJ or PFJ at 11 years was seen in a respective 23% and 35% of people who had rehabilitation with delayed surgery (n = 26) and in 18% and 41% of those who had early surgery (n = 49).
These are descriptive results, Dr. Filbay said, because the numbers were too small to do a statistical analysis. Further, larger, longitudinal studies will be needed.
Posttraumatic OA After ACL Surgery
Elsewhere at OARSI 2024, Matthew Harkey, PhD, and colleagues from Michigan State University, East Lansing, Michigan, reported data showing that nearly two thirds of people who undergo surgical reconstruction have symptoms at 6 months that could be indicative of early knee OA.
Knee symptoms indicative of OA declined to 53% at 12 months and 45% at 24 months.
“It’s a bit complex — we can’t outright say arthritis is developing, but there’s a large group of patients whose symptoms linger long after surgery,” Dr. Harkey said in a press release.
“Often, clinicians assume that these postoperative symptoms will naturally improve as patients reengage with their usual activities. However, what we’re seeing suggests these symptoms persist and likely require a targeted approach to manage or improve them,” Dr. Harkey said.
The analysis used data on 3752 individuals aged 14-40 years who were enrolled in the New Zealand ACL Registry and who completed the KOOS at 6, 12, and 24 months after having ACL reconstruction.
Dr. Harkey and team reported that one in three people had persistent early OA symptoms at 2 years, while 23% had no early OA symptoms at any timepoint.
The studies were independently supported. Dr. Filbay and Dr. Harkey had no relevant financial relationships to report.
Dr. Filbay and colleagues have developed a treatment decision aid for individuals who have sustained an ACL injury. This provides information on the different treatment options available and how they compare.
A version of this article appeared on Medscape.com.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>168078</fileName> <TBEID>0C0501AA.SIG</TBEID> <TBUniqueIdentifier>MD_0C0501AA</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240515T150616</QCDate> <firstPublished>20240515T154441</firstPublished> <LastPublished>20240515T154441</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240515T154441</CMSDate> <articleSource>FROM OARSI 2024</articleSource> <facebookInfo/> <meetingNumber>3588-24</meetingNumber> <byline>Sara Freeman</byline> <bylineText>SARA FREEMAN</bylineText> <bylineFull>SARA FREEMAN</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>VIENNA — Nearly one third of anterior cruciate ligament (ACL) injuries appear to heal without surgery, according to an analysis of three-dimensional MRI data ta</metaDescription> <articlePDF/> <teaserImage>301452</teaserImage> <teaser>Evidence mounts that the anterior cruciate ligament may heal without surgery, but the long-term outcomes are only beginning to be evaluated.</teaser> <title>What Does Natural Healing of ACL Ruptures Mean for Long-Term Outcomes?</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>mdsurg</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle/> <journalFullTitle/> <copyrightStatement>2018 Frontline Medical Communications Inc.,</copyrightStatement> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>52226</term> <term>21</term> <term>15</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">264</term> <term>265</term> <term>237</term> <term>290</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2401294d.jpg</altRep> <description role="drol:caption">Dr. Stephanie Filbay</description> <description role="drol:credit">Sara Freeman/Medscape Medical News</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>What Does Natural Healing of ACL Ruptures Mean for Long-Term Outcomes?</title> <deck/> </itemMeta> <itemContent> <p>VIENNA — Nearly one third of anterior cruciate ligament (ACL) injuries appear to heal without surgery, according to an analysis of three-dimensional MRI data taken from the <span class="Hyperlink"><a href="https://clinicaltrials.gov/study/NCT02931084">NACOX</a></span> study, presented as a late-breaking poster at the <span class="Hyperlink"><a href="https://www.medscape.com/viewcollection/37518">OARSI 2024 World Congress</a></span>. </p> <p>At 2 years after injury, three-dimensional MRI showed that 13 of 43 (30%) knees had evidence of normal, continuous ACL fibers. Moreover, a further 14 (33%) knees had a continuous ACL fiber structure following rehabilitation alone. ACL fibers were partly (16%) or completely (21%) ruptured in the remainder of cases.<br/><br/>[[{"fid":"301452","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Stephanie Filbay, associate professor at The University of Melbourne in Melbourne, Australia","field_file_image_credit[und][0][value]":"Sara Freeman/Medscape Medical News","field_file_image_caption[und][0][value]":"Dr. Stephanie Filbay"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]“If you think of the ACL like a rope, when there is continuity, it means those fibers have rejoined,” study coauthor <span class="Hyperlink"><a href="https://mdhs.unimelb.edu.au/research/researcher-profiles2/dr-stephanie-filbay">Stephanie Filbay, PhD</a></span>, an associate professor at the University of Melbourne in Australia, told this news organization.<br/><br/>“Within that, there’s a few variations of healing that we’re seeing. Some look like they’ve never been injured, while some have rejoined but appear thinner or longer than a normal ACL,” Dr. Filbay said.<br/><br/>She added: “What all this research is showing is that it’s happening at a much higher rate than we thought possible. And in some of the studies, it looks like ACL healing is associated with very favorable outcomes.”<br/><br/>At OARSI 2024, Dr. Filbay presented additional data from her and others’ research on the relationships between ACL healing and long-term functional outcomes and osteoarthritis (OA) incidence in comparisons between patients’ treatment pathways: Early ACL surgery, rehabilitation followed by delayed surgery, or rehabilitation only.<br/><br/></p> <h2>Healing Without Surgery</h2> <p>The idea that the ACL can heal without surgery is relatively recent and perhaps still not widely accepted as a concept, as Dr. Filbay explained during a <a href="https://congress.oarsi.org/program/sessions/concurrent-session-3-rehabilitation-medicine-and-biomechanics">plenary lecture at the congress</a>. </p> <p>Dr. Filbay explained that the ideal management of ACL injury depends on the severity of knee injury and whether someone’s knee is stable after trying nonsurgical management. Results of the <a href="https://doi.org/10.1016/S0140-6736(22)01424-6">ACL SNNAP trial</a>, for example, have suggested that surgical reconstruction is superior to a rehabilitation strategy for managing non-acute ACL injuries where there are persistent symptoms of instability.<br/><br/>However, there have been two trials — <a href="https://www.bmj.com/content/372/bmj.n375.long">COMPARE</a> performed in the Netherlands and <a href="https://www.bmj.com/content/346/bmj.f232">KANON</a> performed in Sweden — that found that early surgery was no better than a strategy of initial rehabilitation with the option of having a delayed ACL surgery if needed.<br/><br/></p> <h2>What Happens Long Term?</h2> <p>Posttraumatic OA is a well-known long-term consequence of ACL injury. According to a <a href="https://journals.lww.com/cjsportsmed/abstract/2022/03000/anterior_cruciate_ligament_injury_and_knee.13.aspx">recent meta-analysis</a>, there is a sevenfold increased risk for OA comparing people who have and have not had an ACL injury.</p> <p>ACL injury also results in OA occurring at an earlier age than in people with OA who have not had an ACL injury. This has been shown to progress at a faster rate and be associated with a longer period of disability, Dr. Filbay said at the congress, sponsored by the Osteoarthritis Research Society International.<br/><br/>But does the ACL really heal? Dr. Filbay thinks that it does and has been involved in several studies that have used MRI to look at how the ACL may do so.<br/><br/>In a <a href="https://bjsm.bmj.com/content/57/2/91">recently published paper</a>, Dr. Filbay and colleagues reported the findings from a secondary analysis of the KANON trial and found that nearly one in three (30%) of the participants who had been randomized to optional delayed surgery had MRI evidence of healing at 2 years. But when they excluded people who had delayed surgery, 53% of people managed by rehabilitation alone had evidence of healing.<br/><br/>The evaluation also found that those who had a healed vs non-healed ligament had better results using the Knee Injury and Osteoarthritis Outcome Score (KOOS), and that there were better outcomes at 2 years among those with ACL healing vs those who had early or delayed ACL surgery.<br/><br/></p> <h2>ACL Continuity and Long-Term Outcomes</h2> <p>At OARSI 2024, Dr. Filbay and colleagues reported an even longer-term <a href="https://www.sciencedirect.com/science/article/abs/pii/S1063458424000724">secondary analysis of the KANON trial</a> on the relationship between ACL healing at 5 years and outcomes at 11 years. The results were <a href="https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200287">first reported</a> in <em>NEJM Evidence</em>.</p> <p>Dr. Filbay reported that participants with ACL continuity on MRI at 5 years actually had worse patient-reported outcomes 11 years later than those who were managed with early or delayed ACL reconstruction.<br/><br/>“This does not align with previous findings suggesting better 2-year outcomes compared to the surgically managed groups,” Dr. Filbay said.<br/><br/>However, people with ACL continuity following rehabilitation did seem to show numerically similar or fewer signs of radiographic OA at 11 years vs the surgical groups.<br/><br/>Radiographic OA of the tibiofemoral joint (TFJ) or patellofemoral joint (PFJ) at 11 years was observed in a respective 14% and 21% of people with ACL continuity at 5 years (n = 14) and in 22% and 11% of people with ACL discontinuity at 5 years in the rehabilitation alone group.<br/><br/>By comparison, radiographic OA of the TFJ or PFJ at 11 years was seen in a respective 23% and 35% of people who had rehabilitation with delayed surgery (n = 26) and in 18% and 41% of those who had early surgery (n = 49).<br/><br/>These are descriptive results, Dr. Filbay said, because the numbers were too small to do a statistical analysis. Further, larger, longitudinal studies will be needed.<br/><br/></p> <h2>Posttraumatic OA After ACL Surgery</h2> <p>Elsewhere at OARSI 2024, <a href="https://education.msu.edu/people/harkey-matt/">Matthew Harkey</a>, PhD, and colleagues from Michigan State University, East Lansing, Michigan, <a href="https://www.sciencedirect.com/science/article/abs/pii/S1063458424004035">reported data</a> showing that nearly two thirds of people who undergo surgical reconstruction have symptoms at 6 months that could be indicative of early knee OA.</p> <p>Knee symptoms indicative of OA declined to 53% at 12 months and 45% at 24 months.<br/><br/>“It’s a bit complex — we can’t outright say arthritis is developing, but there’s a large group of patients whose symptoms linger long after surgery,” Dr. Harkey said in a <a href="https://www.eurekalert.org/news-releases/1040502">press release</a>.<br/><br/>“Often, clinicians assume that these postoperative symptoms will naturally improve as patients reengage with their usual activities. However, what we’re seeing suggests these symptoms persist and likely require a targeted approach to manage or improve them,” Dr. Harkey said.<br/><br/>The analysis used data on 3752 individuals aged 14-40 years who were enrolled in the <a href="https://www.aclregistry.nz/">New Zealand ACL Registry</a> and who completed the KOOS at 6, 12, and 24 months after having ACL reconstruction.<br/><br/>Dr. Harkey and team reported that one in three people had persistent early OA symptoms at 2 years, while 23% had no early OA symptoms at any timepoint.<br/><br/>The studies were independently supported. Dr. Filbay and Dr. Harkey had no relevant financial relationships to report.<br/><br/>Dr. Filbay and colleagues have developed a <a href="https://www.aclinjurytreatment.com/">treatment decision aid</a> for individuals who have sustained an ACL injury. This provides information on the different treatment options available and how they compare.<span class="end"/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/one-third-anterior-cruciate-ligament-ruptures-heal-naturally-2024a100094e">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM OARSI 2024
Will Diabetes Drugs Advance Osteoarthritis Management?
VIENNA — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) recently shown to significantly induce weight loss in people with osteoarthritis (OA) and obesity in the STEP-9 trial, could drugs traditionally used to treat type 2 diabetes be the next big thing for OA management?
“Hormone-based weight loss drugs are a game changer” for obesity management, Sébastien Czernichow, MD, PhD, said during a plenary session at the OARSI 2024 World Congress.
Drugs such as semaglutide may also have a cardioprotective effect, reducing the risk for major adverse cardiovascular events by as much as 20% vs placebo, added Dr. Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France.
“You have to keep in mind that the short-term side effects are mainly gastrointestinal and [are] manageable. The mid-term side effects are an increased gallbladder [disease] risk, and the long-term benefits and risks are not really well known yet,” Dr. Czernichow said. With regard to that, the effects of these drugs on lean body mass, bone health, and nutritional deficiencies need to be further evaluated and monitored.
Weight Loss Benefits
Weight loss is one of the cornerstones of OA management, and in addition to the weight loss seen with the GLP-1 receptor agonists, there have also been changes in body composition, Dr. Czernichow said.
In SURMOUNT-1, for example, the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide (Zepbound) was shown to significantly reduce total fat mass with a smaller decrease in total lean mass in a subanalysis.
It has been argued that effects on body composition need to be considered when evaluating new weight loss drugs, and that focusing only on the degree of weight reduction is “encouraging inaccurate measures of medication efficacy for both patients and clinicians,” Dr. Czernichow said, citing a viewpoint published in JAMA Internal Medicine.
“The real question is: Are we able to fund these drugs for everyone? Or will only the richest patients be allocated to these drugs?” Dr. Czernichow said.
Weight Rebound
Tonia Vincent, MBBS, PhD, professor of musculoskeletal biology and an honorary rheumatologist at The Kennedy Institute of Rheumatology at University of Oxford in England, was concerned about rebound weight gain.
“We hear a lot about this, that people stopping drugs actually get worse weight gain than before they started, and that’s a concern about a drug that is going to have a huge pressure for supply,” Dr. Vincent said following Dr. Czernichow’s presentation.
Another delegate said that calling GLP-1 receptor agonists a “game changer” for weight loss in OA was premature because long-term results are needed.
“You mentioned that the double-digit weight loss is getting very close to the results from bariatric surgery, but bariatric surgery you do once, and for these drugs, to maintain the weight loss, you need to take them continuously,” she said.
Weight Loss Affects Bone
Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.
Separately at OARSI 2024, Anne C. Bay-Jensen, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues reported data showing that weight loss was associated with an increase in bone and cartilage degradation.
Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.
Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.
GLP-1 and Bone Effects
Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.
Dr. Çiftci and researchers reported the findings of an in vitro study that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”
The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for articular cartilage function — also was preserved.
These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.
New Role for Dipeptidyl Transferase Inhibitors?
Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.
Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.
“Last year, we published a paper where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”
For their analysis, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.
Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).
DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.
Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”
Could Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors Be Beneficial?
So, what about SGLT2 inhibitors? Do they also have a potential role to play in managing people with OA, regardless of whether there is diabetes present? Perhaps, and their effect may be even greater than what’s been observed for GLP-1 receptor agonists, as data presented by epidemiologist S. Reza Jafarzadeh, DVM, PhD, suggested.
“While GLP-1 receptor agonist drugs have been reported to reduce OA risk, largely attributed to their weight loss effect, SGLT2 inhibitors may provide a greater protective effect on OA outcomes,” said Dr. Jafarzadeh, assistant professor at Boston University.
He presented data from a large analysis of new users of SGLT2 inhibitors and GLP-1 receptor agonists within two claims databases — Merative (n = 603,471) and TriNetX (n = 1,202,972) — showing that SGLT2 inhibitors were associated with significantly lower risks for OA and the need for TKR.
Comparing new users of SGLT2 inhibitors and GLP-1 receptor agonists in the Merative dataset, the relative risks and odds ratios for OA were a respective 0.96 and 0.80, and having a TKR, 0.88 and 0.76.
Similar results were seen using the TriNetX dataset, with respective relative risks and hazard ratios of 0.90 and 0.85 for OA, and 0.81 and 0.78 for TKR.
In an interview, Dr. Jafarzadeh said that the initial hypothesis was that because SGLT2 inhibitors have only a modest effect on weight loss, there would be no effect on OA outcomes.
“But we were surprised that it actually looked like they reduced the risk of OA outcomes even more than GLP-1 receptor agonists,” Dr. Jafarzadeh said.
Further work is needed to understand these data, but they could mean that SLGT2 inhibitors, like GLP-1 receptor agonists, may have a role to play outside their current use in type 2 diabetes.
The congress was sponsored by the Osteoarthritis Research Society International.
Dr. Czernichow disclosed ties with BariaTek Medical, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Jellynov, Lilly, Novo Nordisk, Novartis, and ViiV Healthcare. Dr. Vincent had no relevant disclosures. Dr. Bay-Jensen is the chief technology officer and director of immunoscience at Nordic Bioscience, which funded the work in the poster she presented at OARSI 2024. The work presented by Dr. Çiftci and colleagues was funded by the Eurostars-2 joint program with co-funding from the European Horizon 2020 research and innovation program. Dr. Çiftci had no personal disclosures to report. Dr. Chen’s work was supported by the government of Taiwan, and she had no financial conflicts of interest to disclose. Dr. Jafarzadeh had no conflicts of interest to disclose.
A version of this article appeared on Medscape.com .
VIENNA — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) recently shown to significantly induce weight loss in people with osteoarthritis (OA) and obesity in the STEP-9 trial, could drugs traditionally used to treat type 2 diabetes be the next big thing for OA management?
“Hormone-based weight loss drugs are a game changer” for obesity management, Sébastien Czernichow, MD, PhD, said during a plenary session at the OARSI 2024 World Congress.
Drugs such as semaglutide may also have a cardioprotective effect, reducing the risk for major adverse cardiovascular events by as much as 20% vs placebo, added Dr. Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France.
“You have to keep in mind that the short-term side effects are mainly gastrointestinal and [are] manageable. The mid-term side effects are an increased gallbladder [disease] risk, and the long-term benefits and risks are not really well known yet,” Dr. Czernichow said. With regard to that, the effects of these drugs on lean body mass, bone health, and nutritional deficiencies need to be further evaluated and monitored.
Weight Loss Benefits
Weight loss is one of the cornerstones of OA management, and in addition to the weight loss seen with the GLP-1 receptor agonists, there have also been changes in body composition, Dr. Czernichow said.
In SURMOUNT-1, for example, the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide (Zepbound) was shown to significantly reduce total fat mass with a smaller decrease in total lean mass in a subanalysis.
It has been argued that effects on body composition need to be considered when evaluating new weight loss drugs, and that focusing only on the degree of weight reduction is “encouraging inaccurate measures of medication efficacy for both patients and clinicians,” Dr. Czernichow said, citing a viewpoint published in JAMA Internal Medicine.
“The real question is: Are we able to fund these drugs for everyone? Or will only the richest patients be allocated to these drugs?” Dr. Czernichow said.
Weight Rebound
Tonia Vincent, MBBS, PhD, professor of musculoskeletal biology and an honorary rheumatologist at The Kennedy Institute of Rheumatology at University of Oxford in England, was concerned about rebound weight gain.
“We hear a lot about this, that people stopping drugs actually get worse weight gain than before they started, and that’s a concern about a drug that is going to have a huge pressure for supply,” Dr. Vincent said following Dr. Czernichow’s presentation.
Another delegate said that calling GLP-1 receptor agonists a “game changer” for weight loss in OA was premature because long-term results are needed.
“You mentioned that the double-digit weight loss is getting very close to the results from bariatric surgery, but bariatric surgery you do once, and for these drugs, to maintain the weight loss, you need to take them continuously,” she said.
Weight Loss Affects Bone
Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.
Separately at OARSI 2024, Anne C. Bay-Jensen, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues reported data showing that weight loss was associated with an increase in bone and cartilage degradation.
Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.
Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.
GLP-1 and Bone Effects
Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.
Dr. Çiftci and researchers reported the findings of an in vitro study that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”
The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for articular cartilage function — also was preserved.
These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.
New Role for Dipeptidyl Transferase Inhibitors?
Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.
Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.
“Last year, we published a paper where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”
For their analysis, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.
Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).
DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.
Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”
Could Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors Be Beneficial?
So, what about SGLT2 inhibitors? Do they also have a potential role to play in managing people with OA, regardless of whether there is diabetes present? Perhaps, and their effect may be even greater than what’s been observed for GLP-1 receptor agonists, as data presented by epidemiologist S. Reza Jafarzadeh, DVM, PhD, suggested.
“While GLP-1 receptor agonist drugs have been reported to reduce OA risk, largely attributed to their weight loss effect, SGLT2 inhibitors may provide a greater protective effect on OA outcomes,” said Dr. Jafarzadeh, assistant professor at Boston University.
He presented data from a large analysis of new users of SGLT2 inhibitors and GLP-1 receptor agonists within two claims databases — Merative (n = 603,471) and TriNetX (n = 1,202,972) — showing that SGLT2 inhibitors were associated with significantly lower risks for OA and the need for TKR.
Comparing new users of SGLT2 inhibitors and GLP-1 receptor agonists in the Merative dataset, the relative risks and odds ratios for OA were a respective 0.96 and 0.80, and having a TKR, 0.88 and 0.76.
Similar results were seen using the TriNetX dataset, with respective relative risks and hazard ratios of 0.90 and 0.85 for OA, and 0.81 and 0.78 for TKR.
In an interview, Dr. Jafarzadeh said that the initial hypothesis was that because SGLT2 inhibitors have only a modest effect on weight loss, there would be no effect on OA outcomes.
“But we were surprised that it actually looked like they reduced the risk of OA outcomes even more than GLP-1 receptor agonists,” Dr. Jafarzadeh said.
Further work is needed to understand these data, but they could mean that SLGT2 inhibitors, like GLP-1 receptor agonists, may have a role to play outside their current use in type 2 diabetes.
The congress was sponsored by the Osteoarthritis Research Society International.
Dr. Czernichow disclosed ties with BariaTek Medical, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Jellynov, Lilly, Novo Nordisk, Novartis, and ViiV Healthcare. Dr. Vincent had no relevant disclosures. Dr. Bay-Jensen is the chief technology officer and director of immunoscience at Nordic Bioscience, which funded the work in the poster she presented at OARSI 2024. The work presented by Dr. Çiftci and colleagues was funded by the Eurostars-2 joint program with co-funding from the European Horizon 2020 research and innovation program. Dr. Çiftci had no personal disclosures to report. Dr. Chen’s work was supported by the government of Taiwan, and she had no financial conflicts of interest to disclose. Dr. Jafarzadeh had no conflicts of interest to disclose.
A version of this article appeared on Medscape.com .
VIENNA — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) recently shown to significantly induce weight loss in people with osteoarthritis (OA) and obesity in the STEP-9 trial, could drugs traditionally used to treat type 2 diabetes be the next big thing for OA management?
“Hormone-based weight loss drugs are a game changer” for obesity management, Sébastien Czernichow, MD, PhD, said during a plenary session at the OARSI 2024 World Congress.
Drugs such as semaglutide may also have a cardioprotective effect, reducing the risk for major adverse cardiovascular events by as much as 20% vs placebo, added Dr. Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France.
“You have to keep in mind that the short-term side effects are mainly gastrointestinal and [are] manageable. The mid-term side effects are an increased gallbladder [disease] risk, and the long-term benefits and risks are not really well known yet,” Dr. Czernichow said. With regard to that, the effects of these drugs on lean body mass, bone health, and nutritional deficiencies need to be further evaluated and monitored.
Weight Loss Benefits
Weight loss is one of the cornerstones of OA management, and in addition to the weight loss seen with the GLP-1 receptor agonists, there have also been changes in body composition, Dr. Czernichow said.
In SURMOUNT-1, for example, the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide (Zepbound) was shown to significantly reduce total fat mass with a smaller decrease in total lean mass in a subanalysis.
It has been argued that effects on body composition need to be considered when evaluating new weight loss drugs, and that focusing only on the degree of weight reduction is “encouraging inaccurate measures of medication efficacy for both patients and clinicians,” Dr. Czernichow said, citing a viewpoint published in JAMA Internal Medicine.
“The real question is: Are we able to fund these drugs for everyone? Or will only the richest patients be allocated to these drugs?” Dr. Czernichow said.
Weight Rebound
Tonia Vincent, MBBS, PhD, professor of musculoskeletal biology and an honorary rheumatologist at The Kennedy Institute of Rheumatology at University of Oxford in England, was concerned about rebound weight gain.
“We hear a lot about this, that people stopping drugs actually get worse weight gain than before they started, and that’s a concern about a drug that is going to have a huge pressure for supply,” Dr. Vincent said following Dr. Czernichow’s presentation.
Another delegate said that calling GLP-1 receptor agonists a “game changer” for weight loss in OA was premature because long-term results are needed.
“You mentioned that the double-digit weight loss is getting very close to the results from bariatric surgery, but bariatric surgery you do once, and for these drugs, to maintain the weight loss, you need to take them continuously,” she said.
Weight Loss Affects Bone
Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.
Separately at OARSI 2024, Anne C. Bay-Jensen, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues reported data showing that weight loss was associated with an increase in bone and cartilage degradation.
Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.
Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.
GLP-1 and Bone Effects
Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.
Dr. Çiftci and researchers reported the findings of an in vitro study that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”
The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for articular cartilage function — also was preserved.
These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.
New Role for Dipeptidyl Transferase Inhibitors?
Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.
Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.
“Last year, we published a paper where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”
For their analysis, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.
Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).
DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.
Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”
Could Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors Be Beneficial?
So, what about SGLT2 inhibitors? Do they also have a potential role to play in managing people with OA, regardless of whether there is diabetes present? Perhaps, and their effect may be even greater than what’s been observed for GLP-1 receptor agonists, as data presented by epidemiologist S. Reza Jafarzadeh, DVM, PhD, suggested.
“While GLP-1 receptor agonist drugs have been reported to reduce OA risk, largely attributed to their weight loss effect, SGLT2 inhibitors may provide a greater protective effect on OA outcomes,” said Dr. Jafarzadeh, assistant professor at Boston University.
He presented data from a large analysis of new users of SGLT2 inhibitors and GLP-1 receptor agonists within two claims databases — Merative (n = 603,471) and TriNetX (n = 1,202,972) — showing that SGLT2 inhibitors were associated with significantly lower risks for OA and the need for TKR.
Comparing new users of SGLT2 inhibitors and GLP-1 receptor agonists in the Merative dataset, the relative risks and odds ratios for OA were a respective 0.96 and 0.80, and having a TKR, 0.88 and 0.76.
Similar results were seen using the TriNetX dataset, with respective relative risks and hazard ratios of 0.90 and 0.85 for OA, and 0.81 and 0.78 for TKR.
In an interview, Dr. Jafarzadeh said that the initial hypothesis was that because SGLT2 inhibitors have only a modest effect on weight loss, there would be no effect on OA outcomes.
“But we were surprised that it actually looked like they reduced the risk of OA outcomes even more than GLP-1 receptor agonists,” Dr. Jafarzadeh said.
Further work is needed to understand these data, but they could mean that SLGT2 inhibitors, like GLP-1 receptor agonists, may have a role to play outside their current use in type 2 diabetes.
The congress was sponsored by the Osteoarthritis Research Society International.
Dr. Czernichow disclosed ties with BariaTek Medical, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Jellynov, Lilly, Novo Nordisk, Novartis, and ViiV Healthcare. Dr. Vincent had no relevant disclosures. Dr. Bay-Jensen is the chief technology officer and director of immunoscience at Nordic Bioscience, which funded the work in the poster she presented at OARSI 2024. The work presented by Dr. Çiftci and colleagues was funded by the Eurostars-2 joint program with co-funding from the European Horizon 2020 research and innovation program. Dr. Çiftci had no personal disclosures to report. Dr. Chen’s work was supported by the government of Taiwan, and she had no financial conflicts of interest to disclose. Dr. Jafarzadeh had no conflicts of interest to disclose.
A version of this article appeared on Medscape.com .
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>VIENNA — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) recently shown to significantly induce weight loss in people with osteoart</metaDescription> <articlePDF/> <teaserImage>301453</teaserImage> <teaser>Researchers are looking to see if GLP-1 receptor agonists, DPP4 inhibitors, and SGLT2 inhibitors have beneficial effects in osteoarthritis.</teaser> <title>Will Diabetes Drugs Advance Osteoarthritis Management?</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>34</term> <term>15</term> <term>21</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">265</term> <term>205</term> <term>261</term> <term>290</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2401294e.jpg</altRep> <description role="drol:caption">Dr. Sébastien Czernichow</description> <description role="drol:credit">Sara Freeman/Medscape Medical News</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2401294f.jpg</altRep> <description role="drol:caption">Dr. S Reza Jafarzadeh</description> <description role="drol:credit">Sara Freeman/Medscape Medical News</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Will Diabetes Drugs Advance Osteoarthritis Management?</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">VIENNA</span> — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/semaglutide-improves-knee-osteoarthritis-pain-physical-2024a10007s0">recently shown</a></span> to significantly induce weight loss in people with osteoarthritis (OA) and obesity in the <span class="Hyperlink"><a href="https://clinicaltrials.gov/study/NCT05064735">STEP-9 trial</a></span>, could drugs traditionally used to treat type 2 diabetes be the next big thing for OA management?</p> <p>“Hormone-based weight loss drugs are a game changer” for obesity management, Sébastien Czernichow, MD, PhD, said during a plenary session at the <span class="Hyperlink"><a href="https://www.medscape.com/viewcollection/37518">OARSI 2024 World Congress</a></span>.<br/><br/>[[{"fid":"301453","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Sébastien Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France","field_file_image_credit[und][0][value]":"Sara Freeman/Medscape Medical News","field_file_image_caption[und][0][value]":"Dr. Sébastien Czernichow"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]Drugs such as semaglutide may also have a cardioprotective effect, reducing the risk for major adverse cardiovascular events <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2307563">by as much as 20% vs placebo</a>, added Dr. Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France.<br/><br/>“You have to keep in mind that the short-term side effects are mainly gastrointestinal and [are] manageable. The mid-term side effects are an increased gallbladder [disease] risk, and the long-term benefits and risks are not really well known yet,” Dr. Czernichow said. With regard to that, the effects of these drugs on lean body mass, bone health, and nutritional deficiencies need to be further evaluated and monitored.<br/><br/></p> <h2>Weight Loss Benefits</h2> <p>Weight loss is one of the cornerstones of OA management, and in addition to the weight loss seen with the GLP-1 receptor agonists, there have also been changes in body composition, Dr. Czernichow said.</p> <p>In <a href="https://clinicaltrials.gov/study/NCT04184622">SURMOUNT-1</a>, for example, the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide (Zepbound) was shown to significantly reduce total fat mass with a smaller decrease in total lean mass in a <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2206038">subanalysis</a>.<br/><br/>It has been argued that effects on body composition need to be considered when evaluating new weight loss drugs, and that focusing only on the degree of weight reduction is “encouraging inaccurate measures of medication efficacy for both patients and clinicians,” Dr. Czernichow said, citing a <span class="Hyperlink"><a href="https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2815006">viewpoint published</a></span> in <em>JAMA Internal Medicine</em>.<br/><br/>“The real question is: Are we able to fund these drugs for everyone? Or will only the richest patients be allocated to these drugs?” Dr. Czernichow said.<br/><br/></p> <h2>Weight Rebound</h2> <p><a href="https://www.kennedy.ox.ac.uk/team/tonia-vincent">Tonia Vincent</a>, MBBS, PhD, professor of musculoskeletal biology and an honorary rheumatologist at The Kennedy Institute of Rheumatology at University of Oxford in England, was concerned about rebound weight gain.</p> <p>“We hear a lot about this, that people stopping drugs actually get worse weight gain than before they started, and that’s a concern about a drug that is going to have a huge pressure for supply,” Dr. Vincent said following Dr. Czernichow’s presentation.<br/><br/>Another delegate said that calling GLP-1 receptor agonists a “game changer” for weight loss in OA was premature because long-term results are needed.<br/><br/>“You mentioned that the double-digit weight loss is getting very close to the results from bariatric surgery, but bariatric surgery you do once, and for these drugs, to maintain the weight loss, you need to take them continuously,” she said.<br/><br/></p> <h2>Weight Loss Affects Bone</h2> <p>Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.</p> <p>Separately at OARSI 2024, <a href="https://www.nordicbioscience.com/about/scientific-leadership/anne-christine-bay-jensen-mmba-phd">Anne C. Bay-Jensen</a>, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues <a href="https://www.sciencedirect.com/science/article/abs/pii/S1063458424007878">reported data</a> showing that weight loss was associated with an increase in bone and cartilage degradation.<br/><br/>Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.<br/><br/>Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.<br/><br/></p> <h2>GLP-1 and Bone Effects</h2> <p>Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.</p> <p>Dr. Çiftci and researchers reported the findings of an <a href="https://doi.org/10.1016/j.joca.2024.02.162">in vitro study</a> that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”<br/><br/>The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for <a href="https://www.nature.com/articles/7290106">articular cartilage function</a> — also was preserved.<br/><br/>These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.<br/><br/></p> <h2>New Role for Dipeptidyl Transferase Inhibitors?</h2> <p>Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.</p> <p>Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.<br/><br/>“Last year, we <a href="https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.42455">published a paper</a> where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”<br/><br/>For <a href="https://www.sciencedirect.com/science/article/abs/pii/S1063458424003030">their analysis</a>, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.<br/><br/>Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).<br/><br/>DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.<br/><br/>Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”<br/><br/></p> <h2>Could Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors Be Beneficial?</h2> <p>So, what about SGLT2 inhibitors? Do they also have a potential role to play in managing people with OA, regardless of whether there is diabetes present? Perhaps, and their effect may be even greater than what’s been observed for GLP-1 receptor agonists, as data presented by epidemiologist <a href="https://profiles.bu.edu/Reza.Jafarzadeh">S. Reza Jafarzadeh</a>, DVM, PhD, suggested.</p> <p>“While GLP-1 receptor agonist drugs have been reported to reduce OA risk, largely attributed to their weight loss effect, SGLT2 inhibitors may provide a greater protective effect on OA outcomes,” said Dr. Jafarzadeh, assistant professor at Boston University.[[{"fid":"301454","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. S Reza Jafarzadeh, an epidemiologist and assistant professor at Boston University","field_file_image_credit[und][0][value]":"Sara Freeman/Medscape Medical News","field_file_image_caption[und][0][value]":"Dr. S Reza Jafarzadeh"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]<br/><br/>He presented data from a <span class="Hyperlink"><a href="https://www.sciencedirect.com/science/article/abs/pii/S1063458424001079">large analysis</a></span> of new users of SGLT2 inhibitors and GLP-1 receptor agonists within two claims databases — Merative (n = 603,471) and TriNetX (n = 1,202,972) — showing that SGLT2 inhibitors were associated with significantly lower risks for OA and the need for TKR.<br/><br/>Comparing new users of SGLT2 inhibitors and GLP-1 receptor agonists in the Merative dataset, the relative risks and odds ratios for OA were a respective 0.96 and 0.80, and having a TKR, 0.88 and 0.76.<br/><br/>Similar results were seen using the TriNetX dataset, with respective relative risks and hazard ratios of 0.90 and 0.85 for OA, and 0.81 and 0.78 for TKR.<br/><br/>In an interview, Dr. Jafarzadeh said<span class="Emphasis"> </span>that the initial hypothesis was that because SGLT2 inhibitors have only a modest effect on weight loss, there would be no effect on OA outcomes.<br/><br/>“But we were surprised that it actually looked like they reduced the risk of OA outcomes even more than GLP-1 receptor agonists,” Dr. Jafarzadeh said.<br/><br/>Further work is needed to understand these data, but they could mean that SLGT2 inhibitors, like GLP-1 receptor agonists, may have a role to play outside their current use in type 2 diabetes.<br/><br/>Dr. Czernichow disclosed ties with BariaTek Medical, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Jellynov, Lilly, Novo Nordisk, Novartis, and ViiV Healthcare. Dr. Vincent had no relevant disclosures. Dr. Bay-Jensen is the chief technology officer and director of immunoscience at Nordic Bioscience, which funded the work in the poster she presented at OARSI 2024. The work presented by Dr. Çiftci and colleagues was funded by the Eurostars-2 joint program with co-funding from the European Horizon 2020 research and innovation program. Dr. Çiftci had no personal disclosures to report. Dr. Chen’s work was supported by the government of Taiwan, and she had no financial conflicts of interest to disclose. Dr. Jafarzadeh had no conflicts of interest to disclose.</p> <p> <em> <span class="Emphasis">A version of this article appeared on </span> <span class="Hyperlink"> <a href="https://www.medscape.com/viewarticle/are-diabetes-drugs-set-move-osteoarthritis-management-2024a100094y">Medscape.com</a> </span> <span class="Emphasis">.</span> </em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM OARSI 2024
Monoclonal Antibody With Unique Mechanism Gets Second Chance in RA
LIVERPOOL, ENGLAND — The IRIS-RA study of the investigational monoclonal antibody drug nipocalimab in patients with rheumatoid arthritis (RA) did not meet its primary endpoint, but there could still be people with moderate to severe RA who might benefit from treatment with the drug, according to information reported at the British Society for Rheumatology annual meeting.
The primary endpoint for the phase 2A trial was the least squares mean change in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) from baseline to 12 weeks of treatment. This was reduced by −1.03 with nipocalimab and by −0.58 with placebo, giving a mean difference of just −0.45 (P = .224).
However, one of the key secondary endpoints was the proportion of patients who had 20% improvement in American College of Rheumatology response criteria (ACR20). Results for this endpoint showed a greater difference in response to nipocalimab vs placebo, with a respective 45.5% and 20.0% (P = .055) of individuals achieving ACR20.
Moreover, an analysis stratifying for anti-citrullinated protein autoantibody (ACPA) levels at baseline found that people with higher levels had a better response to nipocalimab.
Choice of Endpoint
“The way this study was powered was to look at a change between the treatment groups of a DAS28-CRP reduction of 1.0,” said Peter C. Taylor, BMBCh, PhD, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in Oxford, England.
DAS28-CRP was often chosen as the primary endpoint in small proof-of-concept studies, such as IRIS-RA, because it was a “measure of continuous change [that] theoretically, would allow greater sensitivity to change,” Dr. Taylor added.
“Ironically, it has to be said that had we chosen ACR20, we would have hit the primary endpoint. One lives and learns,” noted Dr. Taylor.
Proof of Concept
IRIS-RA was billed as a “proof-of-concept” study because it was the first time that a monoclonal antibody targeting the neonatal fragment crystallizable receptor (FcRn) was being tested in an RA population.
The study was a randomized double-blind trial in which 33 people with moderate to severe RA who had an inadequate response to tumor necrosis factor (TNF) inhibitors were treated with nipocalimab at a dose of 15 mg/kg given intravenously every 2 weeks, and 20 received a matching placebo. Participants were treated for 10 weeks, and then the primary follow-up was at 12 weeks, with additional follow-up for safety undertaken at 18 weeks.
Nipocalimab is a fully human, immunoglobulin G1 (IgG1) monoclonal antibody that is designed to selectively block the FcRn. By doing so, it essentially stops IgG from being recycled within the immune system, and this in turn lowers IgG levels. That includes potentially harmful ACPAs, among other pathogenic antibodies, Dr. Taylor and fellow investigators explained in their abstract.
“We’ve known for a long time that ACPA have prognostic value, but there’s been controversy about whether or not ACPA are actually pathogenic,” Dr. Taylor said. “So, one of the hypotheses that this study gives rise to is that by blocking FcRn, and thereby reducing, potentially, the concentration of ACPA in the blood, will we actually have efficacy in patients?”
Are ACPA Really Lowered?
Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in Leeds, England, questioned the reduction in antibody levels during the discussion that followed.
Although these data had not been presented, Dr. Emery observed that the reduction in IgG was actually greater than that in ACPA, “which is fairly critical. Is it feasible to look to selectively lower normal immunoglobulin over pathogenic autoantibodies?”
Dr. Emery also wanted to know if there “was a floor on the reduction of immunoglobulin” with long-term therapy, “which would be a worry.”
Dr. Taylor responded that total IgG had been reduced by about 65% and ACPA by about 40%. Why this difference exists is not yet clear. It could be because ACPA are part of complexed antibodies.
“Most of these patients are rheumatoid factor [RF]–positive,” said Taylor, pointing out that although IgM “wouldn’t normally be affected by FcRn blockade,” there was a 10% reduction in RF IgM, probably because it was complexed to IgG.
“So, the hypothesis here is that if you look at the clearance of complexes, they’re handled differently in the cytoplasm from the clearance of monomeric IgG. But that’s a hypothesis. It needs further investigation. In vitro, there’s very good, confirmatory evidence to support that. But we’ve yet to explore that more fully in vivo,” Dr. Taylor said.
As for long-term effects, Dr. Taylor responded: “All I can tell you is [that] after the 10-week intervention, that up to an 18-week observation period, immunoglobulin levels recovered very rapidly afterwards. And you mustn’t forget that other isotypes are not affected, unlike rituximab.”
Safety and Other Results
With regard to safety, 27 (82%) of nipocalimab- and 12 (60%) of placebo-treated participants experienced at least one treatment-emergent adverse event (TEAE). The most common, occurring in 10% or more of cases, were RA flares (36.4% for nipocalimab vs 15.0% with placebo), headache (12.1% vs 5.0%), and COVID-19 (12.1% vs 0.0%).
There were three serious TEAEs, all in the nipocalimab-treatment group: One was an infection of a burn that had been present at inclusion, another was a deep vein thrombosis that resolved with apixaban treatment, and the other was an infusion-related reaction that resolved with supportive treatment.
Another notable efficacy finding was the proportion of patients achieving DAS28-CRP remission at 12 weeks in the nipocalimab vs the placebo group was substantially greater if considering only people with high baseline ACPA levels, at a respective 40.0% vs 16.7%, when compared with the total population (21.2% vs 10.0%).
Similar findings were seen for the proportion of patients achieving an ACR50, and there were numerically greater reductions in the components of the ACR response criteria such as tender and swollen joints with nipocalimab vs placebo. All of these were exploratory observations, Dr. Taylor emphasized.
Combination and Further Trials
Further trials of nipocalimab are planned or are already ongoing in systemic lupus erythematosus, active lupus nephritis, Sjögren disease, and five other diseases.
In RA, nipocalimab is now being tested in combination with the TNF inhibitor certolizumab pegol (Cimzia) in the DAISY-RA trial. This is another proof-of-concept, phase 2A trial with a target accrual of 104 patients.
The IRIS-RA study was funded by Janssen Research & Development. Dr. Taylor serves as a consultant to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB and received research funding from Galapagos, among others. Dr. Emery received research grants paid to his institution from AbbVie, Bristol Myers Squibb (BMS), Pfizer, MSD, and Roche; received consultant fees from BMS, AbbVie, Pfizer, MSD, Novartis, Roche, and UCB; and has undertaken clinical trials and provided expert advice to Pfizer, MSD, AbbVie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, and Lilly.
A version of this article appeared on Medscape.com.
LIVERPOOL, ENGLAND — The IRIS-RA study of the investigational monoclonal antibody drug nipocalimab in patients with rheumatoid arthritis (RA) did not meet its primary endpoint, but there could still be people with moderate to severe RA who might benefit from treatment with the drug, according to information reported at the British Society for Rheumatology annual meeting.
The primary endpoint for the phase 2A trial was the least squares mean change in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) from baseline to 12 weeks of treatment. This was reduced by −1.03 with nipocalimab and by −0.58 with placebo, giving a mean difference of just −0.45 (P = .224).
However, one of the key secondary endpoints was the proportion of patients who had 20% improvement in American College of Rheumatology response criteria (ACR20). Results for this endpoint showed a greater difference in response to nipocalimab vs placebo, with a respective 45.5% and 20.0% (P = .055) of individuals achieving ACR20.
Moreover, an analysis stratifying for anti-citrullinated protein autoantibody (ACPA) levels at baseline found that people with higher levels had a better response to nipocalimab.
Choice of Endpoint
“The way this study was powered was to look at a change between the treatment groups of a DAS28-CRP reduction of 1.0,” said Peter C. Taylor, BMBCh, PhD, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in Oxford, England.
DAS28-CRP was often chosen as the primary endpoint in small proof-of-concept studies, such as IRIS-RA, because it was a “measure of continuous change [that] theoretically, would allow greater sensitivity to change,” Dr. Taylor added.
“Ironically, it has to be said that had we chosen ACR20, we would have hit the primary endpoint. One lives and learns,” noted Dr. Taylor.
Proof of Concept
IRIS-RA was billed as a “proof-of-concept” study because it was the first time that a monoclonal antibody targeting the neonatal fragment crystallizable receptor (FcRn) was being tested in an RA population.
The study was a randomized double-blind trial in which 33 people with moderate to severe RA who had an inadequate response to tumor necrosis factor (TNF) inhibitors were treated with nipocalimab at a dose of 15 mg/kg given intravenously every 2 weeks, and 20 received a matching placebo. Participants were treated for 10 weeks, and then the primary follow-up was at 12 weeks, with additional follow-up for safety undertaken at 18 weeks.
Nipocalimab is a fully human, immunoglobulin G1 (IgG1) monoclonal antibody that is designed to selectively block the FcRn. By doing so, it essentially stops IgG from being recycled within the immune system, and this in turn lowers IgG levels. That includes potentially harmful ACPAs, among other pathogenic antibodies, Dr. Taylor and fellow investigators explained in their abstract.
“We’ve known for a long time that ACPA have prognostic value, but there’s been controversy about whether or not ACPA are actually pathogenic,” Dr. Taylor said. “So, one of the hypotheses that this study gives rise to is that by blocking FcRn, and thereby reducing, potentially, the concentration of ACPA in the blood, will we actually have efficacy in patients?”
Are ACPA Really Lowered?
Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in Leeds, England, questioned the reduction in antibody levels during the discussion that followed.
Although these data had not been presented, Dr. Emery observed that the reduction in IgG was actually greater than that in ACPA, “which is fairly critical. Is it feasible to look to selectively lower normal immunoglobulin over pathogenic autoantibodies?”
Dr. Emery also wanted to know if there “was a floor on the reduction of immunoglobulin” with long-term therapy, “which would be a worry.”
Dr. Taylor responded that total IgG had been reduced by about 65% and ACPA by about 40%. Why this difference exists is not yet clear. It could be because ACPA are part of complexed antibodies.
“Most of these patients are rheumatoid factor [RF]–positive,” said Taylor, pointing out that although IgM “wouldn’t normally be affected by FcRn blockade,” there was a 10% reduction in RF IgM, probably because it was complexed to IgG.
“So, the hypothesis here is that if you look at the clearance of complexes, they’re handled differently in the cytoplasm from the clearance of monomeric IgG. But that’s a hypothesis. It needs further investigation. In vitro, there’s very good, confirmatory evidence to support that. But we’ve yet to explore that more fully in vivo,” Dr. Taylor said.
As for long-term effects, Dr. Taylor responded: “All I can tell you is [that] after the 10-week intervention, that up to an 18-week observation period, immunoglobulin levels recovered very rapidly afterwards. And you mustn’t forget that other isotypes are not affected, unlike rituximab.”
Safety and Other Results
With regard to safety, 27 (82%) of nipocalimab- and 12 (60%) of placebo-treated participants experienced at least one treatment-emergent adverse event (TEAE). The most common, occurring in 10% or more of cases, were RA flares (36.4% for nipocalimab vs 15.0% with placebo), headache (12.1% vs 5.0%), and COVID-19 (12.1% vs 0.0%).
There were three serious TEAEs, all in the nipocalimab-treatment group: One was an infection of a burn that had been present at inclusion, another was a deep vein thrombosis that resolved with apixaban treatment, and the other was an infusion-related reaction that resolved with supportive treatment.
Another notable efficacy finding was the proportion of patients achieving DAS28-CRP remission at 12 weeks in the nipocalimab vs the placebo group was substantially greater if considering only people with high baseline ACPA levels, at a respective 40.0% vs 16.7%, when compared with the total population (21.2% vs 10.0%).
Similar findings were seen for the proportion of patients achieving an ACR50, and there were numerically greater reductions in the components of the ACR response criteria such as tender and swollen joints with nipocalimab vs placebo. All of these were exploratory observations, Dr. Taylor emphasized.
Combination and Further Trials
Further trials of nipocalimab are planned or are already ongoing in systemic lupus erythematosus, active lupus nephritis, Sjögren disease, and five other diseases.
In RA, nipocalimab is now being tested in combination with the TNF inhibitor certolizumab pegol (Cimzia) in the DAISY-RA trial. This is another proof-of-concept, phase 2A trial with a target accrual of 104 patients.
The IRIS-RA study was funded by Janssen Research & Development. Dr. Taylor serves as a consultant to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB and received research funding from Galapagos, among others. Dr. Emery received research grants paid to his institution from AbbVie, Bristol Myers Squibb (BMS), Pfizer, MSD, and Roche; received consultant fees from BMS, AbbVie, Pfizer, MSD, Novartis, Roche, and UCB; and has undertaken clinical trials and provided expert advice to Pfizer, MSD, AbbVie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, and Lilly.
A version of this article appeared on Medscape.com.
LIVERPOOL, ENGLAND — The IRIS-RA study of the investigational monoclonal antibody drug nipocalimab in patients with rheumatoid arthritis (RA) did not meet its primary endpoint, but there could still be people with moderate to severe RA who might benefit from treatment with the drug, according to information reported at the British Society for Rheumatology annual meeting.
The primary endpoint for the phase 2A trial was the least squares mean change in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) from baseline to 12 weeks of treatment. This was reduced by −1.03 with nipocalimab and by −0.58 with placebo, giving a mean difference of just −0.45 (P = .224).
However, one of the key secondary endpoints was the proportion of patients who had 20% improvement in American College of Rheumatology response criteria (ACR20). Results for this endpoint showed a greater difference in response to nipocalimab vs placebo, with a respective 45.5% and 20.0% (P = .055) of individuals achieving ACR20.
Moreover, an analysis stratifying for anti-citrullinated protein autoantibody (ACPA) levels at baseline found that people with higher levels had a better response to nipocalimab.
Choice of Endpoint
“The way this study was powered was to look at a change between the treatment groups of a DAS28-CRP reduction of 1.0,” said Peter C. Taylor, BMBCh, PhD, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in Oxford, England.
DAS28-CRP was often chosen as the primary endpoint in small proof-of-concept studies, such as IRIS-RA, because it was a “measure of continuous change [that] theoretically, would allow greater sensitivity to change,” Dr. Taylor added.
“Ironically, it has to be said that had we chosen ACR20, we would have hit the primary endpoint. One lives and learns,” noted Dr. Taylor.
Proof of Concept
IRIS-RA was billed as a “proof-of-concept” study because it was the first time that a monoclonal antibody targeting the neonatal fragment crystallizable receptor (FcRn) was being tested in an RA population.
The study was a randomized double-blind trial in which 33 people with moderate to severe RA who had an inadequate response to tumor necrosis factor (TNF) inhibitors were treated with nipocalimab at a dose of 15 mg/kg given intravenously every 2 weeks, and 20 received a matching placebo. Participants were treated for 10 weeks, and then the primary follow-up was at 12 weeks, with additional follow-up for safety undertaken at 18 weeks.
Nipocalimab is a fully human, immunoglobulin G1 (IgG1) monoclonal antibody that is designed to selectively block the FcRn. By doing so, it essentially stops IgG from being recycled within the immune system, and this in turn lowers IgG levels. That includes potentially harmful ACPAs, among other pathogenic antibodies, Dr. Taylor and fellow investigators explained in their abstract.
“We’ve known for a long time that ACPA have prognostic value, but there’s been controversy about whether or not ACPA are actually pathogenic,” Dr. Taylor said. “So, one of the hypotheses that this study gives rise to is that by blocking FcRn, and thereby reducing, potentially, the concentration of ACPA in the blood, will we actually have efficacy in patients?”
Are ACPA Really Lowered?
Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in Leeds, England, questioned the reduction in antibody levels during the discussion that followed.
Although these data had not been presented, Dr. Emery observed that the reduction in IgG was actually greater than that in ACPA, “which is fairly critical. Is it feasible to look to selectively lower normal immunoglobulin over pathogenic autoantibodies?”
Dr. Emery also wanted to know if there “was a floor on the reduction of immunoglobulin” with long-term therapy, “which would be a worry.”
Dr. Taylor responded that total IgG had been reduced by about 65% and ACPA by about 40%. Why this difference exists is not yet clear. It could be because ACPA are part of complexed antibodies.
“Most of these patients are rheumatoid factor [RF]–positive,” said Taylor, pointing out that although IgM “wouldn’t normally be affected by FcRn blockade,” there was a 10% reduction in RF IgM, probably because it was complexed to IgG.
“So, the hypothesis here is that if you look at the clearance of complexes, they’re handled differently in the cytoplasm from the clearance of monomeric IgG. But that’s a hypothesis. It needs further investigation. In vitro, there’s very good, confirmatory evidence to support that. But we’ve yet to explore that more fully in vivo,” Dr. Taylor said.
As for long-term effects, Dr. Taylor responded: “All I can tell you is [that] after the 10-week intervention, that up to an 18-week observation period, immunoglobulin levels recovered very rapidly afterwards. And you mustn’t forget that other isotypes are not affected, unlike rituximab.”
Safety and Other Results
With regard to safety, 27 (82%) of nipocalimab- and 12 (60%) of placebo-treated participants experienced at least one treatment-emergent adverse event (TEAE). The most common, occurring in 10% or more of cases, were RA flares (36.4% for nipocalimab vs 15.0% with placebo), headache (12.1% vs 5.0%), and COVID-19 (12.1% vs 0.0%).
There were three serious TEAEs, all in the nipocalimab-treatment group: One was an infection of a burn that had been present at inclusion, another was a deep vein thrombosis that resolved with apixaban treatment, and the other was an infusion-related reaction that resolved with supportive treatment.
Another notable efficacy finding was the proportion of patients achieving DAS28-CRP remission at 12 weeks in the nipocalimab vs the placebo group was substantially greater if considering only people with high baseline ACPA levels, at a respective 40.0% vs 16.7%, when compared with the total population (21.2% vs 10.0%).
Similar findings were seen for the proportion of patients achieving an ACR50, and there were numerically greater reductions in the components of the ACR response criteria such as tender and swollen joints with nipocalimab vs placebo. All of these were exploratory observations, Dr. Taylor emphasized.
Combination and Further Trials
Further trials of nipocalimab are planned or are already ongoing in systemic lupus erythematosus, active lupus nephritis, Sjögren disease, and five other diseases.
In RA, nipocalimab is now being tested in combination with the TNF inhibitor certolizumab pegol (Cimzia) in the DAISY-RA trial. This is another proof-of-concept, phase 2A trial with a target accrual of 104 patients.
The IRIS-RA study was funded by Janssen Research & Development. Dr. Taylor serves as a consultant to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB and received research funding from Galapagos, among others. Dr. Emery received research grants paid to his institution from AbbVie, Bristol Myers Squibb (BMS), Pfizer, MSD, and Roche; received consultant fees from BMS, AbbVie, Pfizer, MSD, Novartis, Roche, and UCB; and has undertaken clinical trials and provided expert advice to Pfizer, MSD, AbbVie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, and Lilly.
A version of this article appeared on Medscape.com.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>168049</fileName> <TBEID>0C0500FB.SIG</TBEID> <TBUniqueIdentifier>MD_0C0500FB</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240513T153453</QCDate> <firstPublished>20240513T153731</firstPublished> <LastPublished>20240513T153731</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240513T153731</CMSDate> <articleSource>FROM BSR 2024</articleSource> <facebookInfo/> <meetingNumber>3388-24</meetingNumber> <byline>Sara Freeman</byline> <bylineText>SARA FREEMAN</bylineText> <bylineFull>SARA FREEMAN</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>LIVERPOOL, ENGLAND — The IRIS-RA study of the investigational monoclonal antibody drug nipocalimab in patients with rheumatoid arthritis (RA) did not meet its p</metaDescription> <articlePDF/> <teaserImage>301444</teaserImage> <teaser>The trial proved that nipocalimab reduced IgG antibodies, including anti-citrullinated protein autoantibodies, but the primary endpoint was missed.</teaser> <title>Monoclonal Antibody With Unique Mechanism Gets Second Chance in RA</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">289</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012935.jpg</altRep> <description role="drol:caption">Dr. Peter C. Taylor</description> <description role="drol:credit">Sara Freeman/Medscape Medical News</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24011147.jpg</altRep> <description role="drol:caption">Dr. Paul Emery</description> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Monoclonal Antibody With Unique Mechanism Gets Second Chance in RA</title> <deck/> </itemMeta> <itemContent> <p>LIVERPOOL, ENGLAND — The IRIS-RA study of the investigational monoclonal antibody drug nipocalimab in patients with rheumatoid arthritis (RA) did not meet its primary endpoint, but there could still be people with moderate to severe RA who might benefit from treatment with the drug, according to information reported at the <a href="https://www.medscape.com/viewcollection/37509">British Society for Rheumatology annual meeting</a>.</p> <p>The primary endpoint for <a href="https://clinicaltrials.gov/study/NCT04991753">the phase 2A trial</a> was the least squares mean change in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) from baseline to 12 weeks of treatment. This was reduced by −1.03 with nipocalimab and by −0.58 with placebo, giving a mean difference of just −0.45 (<em>P</em> = .224).<br/><br/>However, one of the key secondary endpoints was the proportion of patients who had 20% improvement in American College of Rheumatology response criteria (ACR20). Results for this endpoint showed a greater difference in response to nipocalimab vs placebo, with a respective 45.5% and 20.0% (<em>P</em> = .055) of individuals achieving ACR20.<br/><br/>Moreover, an analysis stratifying for anti-citrullinated protein autoantibody (ACPA) levels at baseline found that people with higher levels had a better response to nipocalimab.<br/><br/></p> <h2>Choice of Endpoint</h2> <p>“The way this study was powered was to look at a change between the treatment groups of a DAS28-CRP reduction of 1.0,” said <a href="https://www.ndorms.ox.ac.uk/team/peter-taylor">Peter C. Taylor</a>, BMBCh, PhD, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in Oxford, England.</p> <p>DAS28-CRP was often chosen as the primary endpoint in small proof-of-concept studies, such as IRIS-RA, because it was a “measure of continuous change [that] theoretically, would allow greater sensitivity to change,” Dr. Taylor added.[[{"fid":"301444","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Peter C. Taylor, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in Oxford, England","field_file_image_credit[und][0][value]":"Sara Freeman/Medscape Medical News","field_file_image_caption[und][0][value]":"Dr. Peter C. Taylor"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]<br/><br/>“Ironically, it has to be said that had we chosen ACR20, we would have hit the primary endpoint. One lives and learns,” noted Dr. Taylor.<br/><br/></p> <h2>Proof of Concept</h2> <p>IRIS-RA was billed as a “proof-of-concept” study because it was the first time that a monoclonal antibody targeting the neonatal fragment crystallizable receptor (FcRn) was being tested in an RA population.</p> <p>The study was a randomized double-blind trial in which 33 people with moderate to severe RA who had an inadequate response to tumor necrosis factor (TNF) inhibitors were treated with nipocalimab at a dose of 15 mg/kg given intravenously every 2 weeks, and 20 received a matching placebo. Participants were treated for 10 weeks, and then the primary follow-up was at 12 weeks, with additional follow-up for safety undertaken at 18 weeks.<br/><br/>Nipocalimab is a fully human, immunoglobulin G1 (IgG1) monoclonal antibody that is designed to selectively block the FcRn. By doing so, it essentially stops IgG from being recycled within the immune system, and this in turn lowers IgG levels. That includes potentially harmful ACPAs, among other pathogenic antibodies, Dr. Taylor and fellow investigators explained in <a href="https://academic.oup.com/rheumatology/article/63/Supplement_1/keae163.004/7656043">their abstract</a>.<br/><br/>“We’ve known for a long time that ACPA have prognostic value, but there’s been controversy about whether or not ACPA are actually pathogenic,” Dr. Taylor said. “So, one of the hypotheses that this study gives rise to is that by blocking FcRn, and thereby reducing, potentially, the concentration of ACPA in the blood, will we actually have efficacy in patients?”<br/><br/></p> <h2>Are ACPA Really Lowered?</h2> <p><a href="https://medicinehealth.leeds.ac.uk/medicine/staff/308/professor-paul-emery">Paul Emery</a>, MD, Versus Arthritis professor of rheumatology and <a href="https://leedsbrc.nihr.ac.uk/professor-paul-emery-obe-flsw-ma-md-frcp-frcpe-fmedsci-macr/">director of the Leeds Biomedical Research Centre</a> at the University of Leeds in Leeds, England, questioned the reduction in antibody levels during the discussion that followed.[[{"fid":"288998","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Paul Emery, professor of rheumatology and director of the University of Leeds (England) Musculoskeletal Biomedical Research Centre","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Paul Emery"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]</p> <p>Although these data had not been presented, Dr. Emery observed that the reduction in IgG was actually greater than that in ACPA, “which is fairly critical. Is it feasible to look to selectively lower normal immunoglobulin over pathogenic autoantibodies?”<br/><br/>Dr. Emery also wanted to know if there “was a floor on the reduction of immunoglobulin” with long-term therapy, “which would be a worry.”<br/><br/>Dr. Taylor responded that total IgG had been reduced by about 65% and ACPA by about 40%. Why this difference exists is not yet clear. It could be because ACPA are part of complexed antibodies.<br/><br/>“Most of these patients are rheumatoid factor [RF]–positive,” said Taylor, pointing out that although IgM “wouldn’t normally be affected by FcRn blockade,” there was a 10% reduction in RF IgM, probably because it was complexed to IgG.<br/><br/>“So, the hypothesis here is that if you look at the clearance of complexes, they’re handled differently in the cytoplasm from the clearance of monomeric IgG. But that’s a hypothesis. It needs further investigation. In vitro, there’s very good, confirmatory evidence to support that. But we’ve yet to explore that more fully in vivo,” Dr. Taylor said.<br/><br/>As for long-term effects, Dr. Taylor responded: “All I can tell you is [that] after the 10-week intervention, that up to an 18-week observation period, immunoglobulin levels recovered very rapidly afterwards. And you mustn’t forget that other isotypes are not affected, unlike rituximab.”<br/><br/></p> <h2>Safety and Other Results</h2> <p>With regard to safety, 27 (82%) of nipocalimab- and 12 (60%) of placebo-treated participants experienced at least one treatment-emergent adverse event (TEAE). The most common, occurring in 10% or more of cases, were RA flares (36.4% for nipocalimab vs 15.0% with placebo), headache (12.1% vs 5.0%), and COVID-19 (12.1% vs 0.0%).</p> <p>There were three serious TEAEs, all in the nipocalimab-treatment group: One was an infection of a burn that had been present at inclusion, another was a deep vein thrombosis that resolved with apixaban treatment, and the other was an infusion-related reaction that resolved with supportive treatment.<br/><br/>Another notable efficacy finding was the proportion of patients achieving DAS28-CRP remission at 12 weeks in the nipocalimab vs the placebo group was substantially greater if considering only people with high baseline ACPA levels, at a respective 40.0% vs 16.7%, when compared with the total population (21.2% vs 10.0%).<br/><br/>Similar findings were seen for the proportion of patients achieving an ACR50, and there were numerically greater reductions in the components of the ACR response criteria such as tender and swollen joints with nipocalimab vs placebo. All of these were exploratory observations, Dr. Taylor emphasized.<br/><br/></p> <h2>Combination and Further Trials</h2> <p>Further trials of nipocalimab are planned or are already ongoing in <a href="https://clinicaltrials.gov/study/NCT04882878">systemic lupus erythematosus</a>, <a href="https://clinicaltrials.gov/study/NCT04883619">active lupus nephritis</a>, <a href="https://clinicaltrials.gov/study/NCT04968912">Sjögren disease</a>, and five other diseases.</p> <p>In RA, nipocalimab is now being tested in combination with the TNF inhibitor <a href="https://reference.medscape.com/drug/cimzia-certolizumab-pegol-343185">certolizumab pegol</a> (Cimzia) in <a href="https://clinicaltrials.gov/study/NCT06028438">the DAISY-RA trial</a>. This is another proof-of-concept, phase 2A trial with a target accrual of 104 patients.<br/><br/>The IRIS-RA study was funded by Janssen Research & Development. Dr. Taylor serves as a consultant to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB and received research funding from Galapagos, among others. Dr. Emery received research grants paid to his institution from AbbVie, Bristol Myers Squibb (BMS), Pfizer, MSD, and Roche; received consultant fees from BMS, AbbVie, Pfizer, MSD, Novartis, Roche, and UCB; and has undertaken clinical trials and provided expert advice to Pfizer, MSD, AbbVie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, and Lilly.<br/><br/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/nipocalimabs-unique-mechanism-gets-second-chance-rheumatoid-2024a100091h">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM BSR 2024
Diacerein, Resveratrol, Botulinum Toxin Disappoint in Knee Osteoarthritis
VIENNA — Data do not back the use of diacerein or resveratrol for managing the pain of knee osteoarthritis (OA), according to the results of two well-performed, multicenter, double-blind, randomized controlled clinical trials.
During the News in Therapies session at the OARSI 2024 World Congress, the null findings of the DICKENS study and ARTHROL trial were presented alongside a reappraisal of the possible role of botulinum toxin.
DICKENS Study of Diacerein
“The role of diacerein in the treatment of OA is controversial,” acknowledged Dawn Aitken, PhD, associate professor at the University of Tasmania in Hobart, Tasmania, Australia. “There are only a few acceptable quality trials to date, and the results are inconsistent,” Dr. Aitken added.
Indeed, a Cochrane review performed in 2014 had concluded that there was “low-quality evidence that diacerein had a small beneficial effect on pain,” she said. The reported overall effect size on a 100-mm visual analog scale, based on a meta-analysis of 10 trials, has been just −8.65 mm, equating to just a 9% pain reduction.
At the time the DICKENS study was conceived, diacerein was recommended by a number of international guidelines for the management of hip and knee OA, although further, higher-quality studies were needed.
Diacerein blocks interleukin-1 beta, which is one of the key inflammatory markers of OA, so Dr. Aitken and collaborators postulated that perhaps it would work better if used in patients with an inflammatory phenotype.
They set about to test their hypothesis by recruiting 260 individuals with knee OA and MRI-detected effusion synovitis. The participants were then randomly allocated to treatment with either diacerein or a matching placebo for 24 weeks.
Individuals in the diacerein group were treated with an oral dose of 50 mg once daily for the first 2 weeks. If tolerated, the dose was increased to 50 mg twice daily.
No significant improvement in the primary endpoint of knee pain was seen comparing diacerein with placebo, with mean values of 53.2 mm and 56.4 mm, respectively, at 24 weeks using a 0-100 mm visual analog scale where 0 represented no pain and 100 represented the worst pain. It followed that there was no significant difference in the change from baseline to week 24 (−19.9 mm vs −18.6 mm; P = .77).
There was also no difference in the secondary endpoints, which included Western Ontario and McMaster Universities Arthritis Index pain, function, and stiffness. In fact, placebo-treated patients appeared to do better in terms of resolution of effusion synovitis as measured by a repeat MRI and quality of life, Dr. Aitken reported.
“These findings do not support the use of diacerein in treating patients with knee OA and effusion synovitis,” Dr. Aitken concluded.
ARTHROL Trial of Resveratrol
Similarly, negative results were reported for resveratrol from the ARTHROL trial, with 55% of the resveratrol- and 55% of placebo-treated individuals achieving a 20% reduction in knee pain intensity at 3 months. The actual change in knee pain from baseline to 3 months was −15.7 for resveratrol and −15.2 for placebo on a numerical rating scale that went from 0 (no pain) up to 100 (worst pain).
Resveratrol is found naturally in grapes, peanuts, pine cones, and Chinese knotweed, and there is a growing body of evidence that it may have pleiotropic effects, said investigator Christelle Nguyen, PhD, MD, a professor of physical and rehabilitation medicine at Université Paris Cité, Paris, France.
It’s available in a powder form over the counter as a treatment for multiple ailments, but more recently, became available as an oral formulation. Dr. Nguyen and colleagues wanted to know if this would make a difference to OA knee pain when added to usual care.
A double-blind, multicenter, placebo-controlled randomized trial was therefore conducted that involved 142 people with knee OA who had been experiencing knee pain for at least 1 month. The participants were equally randomly allocated to receive either oral resveratrol given as two caplets of 20 mg twice daily for the first week, then once daily for a total of 6 months, or a matched placebo.
There was also no effect of resveratrol vs placebo on a host of secondary outcomes measured at 3 and 6 months.
The interpretation is that oral resveratrol may not be effective in this indication or have a biologic effect on the pain pathway, Dr. Nguyen said.
“Our findings do not support the use of [trans-resveratrol] supplementation in this patented formulation for reducing knee pain in adults with painful knee OA,” she concluded.
Botulinum Toxin: Over But Not Out?
Dr. Nguyen separately reported data from a new systematic review and meta-analysis on the use of intra-articular (IA) botulinum toxin type A (BoNT-A) for knee OA pain.
Seven of the 14 randomized controlled trials included in the meta-analysis had looked specifically at knee OA outcomes in the short, intermediate, and long term.
Results showed a nonsignificant trend favoring BoNT-A use, with the standard mean difference in pain of 0.35 (−0.82; 0.12), −0.27 (−0.61; 0.08), and −0.43 (−1.12; 0.26) for short-, intermediate-, and long-term use, respectively.
In contrast, pain reductions were seen with BoNT-A in three trials that included people with OA of the shoulder or base of the thumb. This begs the question as to whether botulinum toxin may still have a role to play, Dr. Nguyen said in an interview.
“It seems like there may be a positive effect for the shoulder joint and base of the thumb,” she told this news organization.
“So, basically, we found differences between large and small to intermediate joints,” Dr. Nguyen added. “It questions the dilution of botulinum toxin into the joint. If it’s a big joint, maybe the dilution is too high,” she suggested.
This hypothesis will be tested in the upcoming RHIBOT II trial that will begin recruitment later this year. This is a follow-on from the RHIBOT trial that was published in The Lancet Rheumatology 2 years ago.
Meanwhile, the use of botulinum toxin is off-label, Dr. Nguyen said. “We use it in our clinics only when first-line treatment had failed for base of thumb OA.” It’s not offered as a stand-alone intervention, and the IA injections need to be given by someone with experience, she said.
Methodologically Sound Studies
Commenting on the studies, Nancy E. Lane, MD, said: “There have been small botulinum studies before but not powered enough so that you could confirm or refute hypotheses.”
Dr. Lane, endowed professor of medicine, rheumatology, and aging research and director for the Center for Musculoskeletal Health at the University of California Davis School of Medicine, Sacramento, California, added: “Similarly for resveratrol, there have been lots of studies.”
Moreover, Dr. Lane observed that the studies were “really well-designed. They were well-powered. The subjects were selected in such a way that was good rigor in the methodologic design, and there were enough people in the studies so that you could really believe the results.”
The take-home is probably that these approaches do not work, Dr. Lane said, “at least when you apply them to moderate-severe knee OA patients, they don’t seem to make a difference.”
The congress was sponsored by the Osteoarthritis Research Society International.
The DICKENS study of diacerein was an investigator-initiated trial that was funded by the National Health and Medical Research Council of Australia. TRB Chemedica International S.A. provided diacerein free of charge for the trial but was not involved in the implementation or data analysis. Dr. Aitken had no conflicts of interest to disclose.
The ARTHROL trial of oral resveratrol was funded by the French Ministry of Health and Solidarity (Ministré des Solidarités et de la Santé). Yvery Laboratory provided the resveratrol caplet and matching placebo free of charge. Dr. Nguyen has financial relationships with Actelion, Grünenthal, Ipsen, Lilly, Meda, Merz, Novartis, Preciphar, Sandoz, Takeda, Thuasne, and UCB.
Dr. Lane had no relevant conflicts of interest to declare.
A version of this article appeared on Medscape.com.
VIENNA — Data do not back the use of diacerein or resveratrol for managing the pain of knee osteoarthritis (OA), according to the results of two well-performed, multicenter, double-blind, randomized controlled clinical trials.
During the News in Therapies session at the OARSI 2024 World Congress, the null findings of the DICKENS study and ARTHROL trial were presented alongside a reappraisal of the possible role of botulinum toxin.
DICKENS Study of Diacerein
“The role of diacerein in the treatment of OA is controversial,” acknowledged Dawn Aitken, PhD, associate professor at the University of Tasmania in Hobart, Tasmania, Australia. “There are only a few acceptable quality trials to date, and the results are inconsistent,” Dr. Aitken added.
Indeed, a Cochrane review performed in 2014 had concluded that there was “low-quality evidence that diacerein had a small beneficial effect on pain,” she said. The reported overall effect size on a 100-mm visual analog scale, based on a meta-analysis of 10 trials, has been just −8.65 mm, equating to just a 9% pain reduction.
At the time the DICKENS study was conceived, diacerein was recommended by a number of international guidelines for the management of hip and knee OA, although further, higher-quality studies were needed.
Diacerein blocks interleukin-1 beta, which is one of the key inflammatory markers of OA, so Dr. Aitken and collaborators postulated that perhaps it would work better if used in patients with an inflammatory phenotype.
They set about to test their hypothesis by recruiting 260 individuals with knee OA and MRI-detected effusion synovitis. The participants were then randomly allocated to treatment with either diacerein or a matching placebo for 24 weeks.
Individuals in the diacerein group were treated with an oral dose of 50 mg once daily for the first 2 weeks. If tolerated, the dose was increased to 50 mg twice daily.
No significant improvement in the primary endpoint of knee pain was seen comparing diacerein with placebo, with mean values of 53.2 mm and 56.4 mm, respectively, at 24 weeks using a 0-100 mm visual analog scale where 0 represented no pain and 100 represented the worst pain. It followed that there was no significant difference in the change from baseline to week 24 (−19.9 mm vs −18.6 mm; P = .77).
There was also no difference in the secondary endpoints, which included Western Ontario and McMaster Universities Arthritis Index pain, function, and stiffness. In fact, placebo-treated patients appeared to do better in terms of resolution of effusion synovitis as measured by a repeat MRI and quality of life, Dr. Aitken reported.
“These findings do not support the use of diacerein in treating patients with knee OA and effusion synovitis,” Dr. Aitken concluded.
ARTHROL Trial of Resveratrol
Similarly, negative results were reported for resveratrol from the ARTHROL trial, with 55% of the resveratrol- and 55% of placebo-treated individuals achieving a 20% reduction in knee pain intensity at 3 months. The actual change in knee pain from baseline to 3 months was −15.7 for resveratrol and −15.2 for placebo on a numerical rating scale that went from 0 (no pain) up to 100 (worst pain).
Resveratrol is found naturally in grapes, peanuts, pine cones, and Chinese knotweed, and there is a growing body of evidence that it may have pleiotropic effects, said investigator Christelle Nguyen, PhD, MD, a professor of physical and rehabilitation medicine at Université Paris Cité, Paris, France.
It’s available in a powder form over the counter as a treatment for multiple ailments, but more recently, became available as an oral formulation. Dr. Nguyen and colleagues wanted to know if this would make a difference to OA knee pain when added to usual care.
A double-blind, multicenter, placebo-controlled randomized trial was therefore conducted that involved 142 people with knee OA who had been experiencing knee pain for at least 1 month. The participants were equally randomly allocated to receive either oral resveratrol given as two caplets of 20 mg twice daily for the first week, then once daily for a total of 6 months, or a matched placebo.
There was also no effect of resveratrol vs placebo on a host of secondary outcomes measured at 3 and 6 months.
The interpretation is that oral resveratrol may not be effective in this indication or have a biologic effect on the pain pathway, Dr. Nguyen said.
“Our findings do not support the use of [trans-resveratrol] supplementation in this patented formulation for reducing knee pain in adults with painful knee OA,” she concluded.
Botulinum Toxin: Over But Not Out?
Dr. Nguyen separately reported data from a new systematic review and meta-analysis on the use of intra-articular (IA) botulinum toxin type A (BoNT-A) for knee OA pain.
Seven of the 14 randomized controlled trials included in the meta-analysis had looked specifically at knee OA outcomes in the short, intermediate, and long term.
Results showed a nonsignificant trend favoring BoNT-A use, with the standard mean difference in pain of 0.35 (−0.82; 0.12), −0.27 (−0.61; 0.08), and −0.43 (−1.12; 0.26) for short-, intermediate-, and long-term use, respectively.
In contrast, pain reductions were seen with BoNT-A in three trials that included people with OA of the shoulder or base of the thumb. This begs the question as to whether botulinum toxin may still have a role to play, Dr. Nguyen said in an interview.
“It seems like there may be a positive effect for the shoulder joint and base of the thumb,” she told this news organization.
“So, basically, we found differences between large and small to intermediate joints,” Dr. Nguyen added. “It questions the dilution of botulinum toxin into the joint. If it’s a big joint, maybe the dilution is too high,” she suggested.
This hypothesis will be tested in the upcoming RHIBOT II trial that will begin recruitment later this year. This is a follow-on from the RHIBOT trial that was published in The Lancet Rheumatology 2 years ago.
Meanwhile, the use of botulinum toxin is off-label, Dr. Nguyen said. “We use it in our clinics only when first-line treatment had failed for base of thumb OA.” It’s not offered as a stand-alone intervention, and the IA injections need to be given by someone with experience, she said.
Methodologically Sound Studies
Commenting on the studies, Nancy E. Lane, MD, said: “There have been small botulinum studies before but not powered enough so that you could confirm or refute hypotheses.”
Dr. Lane, endowed professor of medicine, rheumatology, and aging research and director for the Center for Musculoskeletal Health at the University of California Davis School of Medicine, Sacramento, California, added: “Similarly for resveratrol, there have been lots of studies.”
Moreover, Dr. Lane observed that the studies were “really well-designed. They were well-powered. The subjects were selected in such a way that was good rigor in the methodologic design, and there were enough people in the studies so that you could really believe the results.”
The take-home is probably that these approaches do not work, Dr. Lane said, “at least when you apply them to moderate-severe knee OA patients, they don’t seem to make a difference.”
The congress was sponsored by the Osteoarthritis Research Society International.
The DICKENS study of diacerein was an investigator-initiated trial that was funded by the National Health and Medical Research Council of Australia. TRB Chemedica International S.A. provided diacerein free of charge for the trial but was not involved in the implementation or data analysis. Dr. Aitken had no conflicts of interest to disclose.
The ARTHROL trial of oral resveratrol was funded by the French Ministry of Health and Solidarity (Ministré des Solidarités et de la Santé). Yvery Laboratory provided the resveratrol caplet and matching placebo free of charge. Dr. Nguyen has financial relationships with Actelion, Grünenthal, Ipsen, Lilly, Meda, Merz, Novartis, Preciphar, Sandoz, Takeda, Thuasne, and UCB.
Dr. Lane had no relevant conflicts of interest to declare.
A version of this article appeared on Medscape.com.
VIENNA — Data do not back the use of diacerein or resveratrol for managing the pain of knee osteoarthritis (OA), according to the results of two well-performed, multicenter, double-blind, randomized controlled clinical trials.
During the News in Therapies session at the OARSI 2024 World Congress, the null findings of the DICKENS study and ARTHROL trial were presented alongside a reappraisal of the possible role of botulinum toxin.
DICKENS Study of Diacerein
“The role of diacerein in the treatment of OA is controversial,” acknowledged Dawn Aitken, PhD, associate professor at the University of Tasmania in Hobart, Tasmania, Australia. “There are only a few acceptable quality trials to date, and the results are inconsistent,” Dr. Aitken added.
Indeed, a Cochrane review performed in 2014 had concluded that there was “low-quality evidence that diacerein had a small beneficial effect on pain,” she said. The reported overall effect size on a 100-mm visual analog scale, based on a meta-analysis of 10 trials, has been just −8.65 mm, equating to just a 9% pain reduction.
At the time the DICKENS study was conceived, diacerein was recommended by a number of international guidelines for the management of hip and knee OA, although further, higher-quality studies were needed.
Diacerein blocks interleukin-1 beta, which is one of the key inflammatory markers of OA, so Dr. Aitken and collaborators postulated that perhaps it would work better if used in patients with an inflammatory phenotype.
They set about to test their hypothesis by recruiting 260 individuals with knee OA and MRI-detected effusion synovitis. The participants were then randomly allocated to treatment with either diacerein or a matching placebo for 24 weeks.
Individuals in the diacerein group were treated with an oral dose of 50 mg once daily for the first 2 weeks. If tolerated, the dose was increased to 50 mg twice daily.
No significant improvement in the primary endpoint of knee pain was seen comparing diacerein with placebo, with mean values of 53.2 mm and 56.4 mm, respectively, at 24 weeks using a 0-100 mm visual analog scale where 0 represented no pain and 100 represented the worst pain. It followed that there was no significant difference in the change from baseline to week 24 (−19.9 mm vs −18.6 mm; P = .77).
There was also no difference in the secondary endpoints, which included Western Ontario and McMaster Universities Arthritis Index pain, function, and stiffness. In fact, placebo-treated patients appeared to do better in terms of resolution of effusion synovitis as measured by a repeat MRI and quality of life, Dr. Aitken reported.
“These findings do not support the use of diacerein in treating patients with knee OA and effusion synovitis,” Dr. Aitken concluded.
ARTHROL Trial of Resveratrol
Similarly, negative results were reported for resveratrol from the ARTHROL trial, with 55% of the resveratrol- and 55% of placebo-treated individuals achieving a 20% reduction in knee pain intensity at 3 months. The actual change in knee pain from baseline to 3 months was −15.7 for resveratrol and −15.2 for placebo on a numerical rating scale that went from 0 (no pain) up to 100 (worst pain).
Resveratrol is found naturally in grapes, peanuts, pine cones, and Chinese knotweed, and there is a growing body of evidence that it may have pleiotropic effects, said investigator Christelle Nguyen, PhD, MD, a professor of physical and rehabilitation medicine at Université Paris Cité, Paris, France.
It’s available in a powder form over the counter as a treatment for multiple ailments, but more recently, became available as an oral formulation. Dr. Nguyen and colleagues wanted to know if this would make a difference to OA knee pain when added to usual care.
A double-blind, multicenter, placebo-controlled randomized trial was therefore conducted that involved 142 people with knee OA who had been experiencing knee pain for at least 1 month. The participants were equally randomly allocated to receive either oral resveratrol given as two caplets of 20 mg twice daily for the first week, then once daily for a total of 6 months, or a matched placebo.
There was also no effect of resveratrol vs placebo on a host of secondary outcomes measured at 3 and 6 months.
The interpretation is that oral resveratrol may not be effective in this indication or have a biologic effect on the pain pathway, Dr. Nguyen said.
“Our findings do not support the use of [trans-resveratrol] supplementation in this patented formulation for reducing knee pain in adults with painful knee OA,” she concluded.
Botulinum Toxin: Over But Not Out?
Dr. Nguyen separately reported data from a new systematic review and meta-analysis on the use of intra-articular (IA) botulinum toxin type A (BoNT-A) for knee OA pain.
Seven of the 14 randomized controlled trials included in the meta-analysis had looked specifically at knee OA outcomes in the short, intermediate, and long term.
Results showed a nonsignificant trend favoring BoNT-A use, with the standard mean difference in pain of 0.35 (−0.82; 0.12), −0.27 (−0.61; 0.08), and −0.43 (−1.12; 0.26) for short-, intermediate-, and long-term use, respectively.
In contrast, pain reductions were seen with BoNT-A in three trials that included people with OA of the shoulder or base of the thumb. This begs the question as to whether botulinum toxin may still have a role to play, Dr. Nguyen said in an interview.
“It seems like there may be a positive effect for the shoulder joint and base of the thumb,” she told this news organization.
“So, basically, we found differences between large and small to intermediate joints,” Dr. Nguyen added. “It questions the dilution of botulinum toxin into the joint. If it’s a big joint, maybe the dilution is too high,” she suggested.
This hypothesis will be tested in the upcoming RHIBOT II trial that will begin recruitment later this year. This is a follow-on from the RHIBOT trial that was published in The Lancet Rheumatology 2 years ago.
Meanwhile, the use of botulinum toxin is off-label, Dr. Nguyen said. “We use it in our clinics only when first-line treatment had failed for base of thumb OA.” It’s not offered as a stand-alone intervention, and the IA injections need to be given by someone with experience, she said.
Methodologically Sound Studies
Commenting on the studies, Nancy E. Lane, MD, said: “There have been small botulinum studies before but not powered enough so that you could confirm or refute hypotheses.”
Dr. Lane, endowed professor of medicine, rheumatology, and aging research and director for the Center for Musculoskeletal Health at the University of California Davis School of Medicine, Sacramento, California, added: “Similarly for resveratrol, there have been lots of studies.”
Moreover, Dr. Lane observed that the studies were “really well-designed. They were well-powered. The subjects were selected in such a way that was good rigor in the methodologic design, and there were enough people in the studies so that you could really believe the results.”
The take-home is probably that these approaches do not work, Dr. Lane said, “at least when you apply them to moderate-severe knee OA patients, they don’t seem to make a difference.”
The congress was sponsored by the Osteoarthritis Research Society International.
The DICKENS study of diacerein was an investigator-initiated trial that was funded by the National Health and Medical Research Council of Australia. TRB Chemedica International S.A. provided diacerein free of charge for the trial but was not involved in the implementation or data analysis. Dr. Aitken had no conflicts of interest to disclose.
The ARTHROL trial of oral resveratrol was funded by the French Ministry of Health and Solidarity (Ministré des Solidarités et de la Santé). Yvery Laboratory provided the resveratrol caplet and matching placebo free of charge. Dr. Nguyen has financial relationships with Actelion, Grünenthal, Ipsen, Lilly, Meda, Merz, Novartis, Preciphar, Sandoz, Takeda, Thuasne, and UCB.
Dr. Lane had no relevant conflicts of interest to declare.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>VIENNA — Data do not back the use of diacerein or resveratrol for managing the pain of knee osteoarthritis (OA), according to the results of two well-performed,</metaDescription> <articlePDF/> <teaserImage>195552</teaserImage> <teaser>Data do not back the use of diacerein, resveratrol, or botulinum toxin for knee OA, according to the results of well-performed, multicenter, randomized controlled clinical trials.</teaser> <title>Diacerein, Resveratrol, Botulinum Toxin Disappoint in Knee Osteoarthritis</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>21</term> <term>15</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">265</term> <term>290</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2400777b.jpg</altRep> <description role="drol:caption">Dr. Dawn Aitken</description> <description role="drol:credit">Bruce Jancin/MDedge News</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012907.jpg</altRep> <description role="drol:caption">Dr. Christelle Nguyen</description> <description role="drol:credit">Sara Freeman/Medscape Medical News</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Diacerein, Resveratrol, Botulinum Toxin Disappoint in Knee Osteoarthritis</title> <deck/> </itemMeta> <itemContent> <p>VIENNA — Data do not back the use of diacerein or resveratrol for managing the pain of knee osteoarthritis (OA), according to the results of two well-performed, multicenter, double-blind, randomized controlled clinical trials.</p> <p>During the <a href="https://congress.oarsi.org/program/sessions/concurrent-session-09-news-therapies">News in Therapies</a> session at the <a href="https://www.medscape.com/viewcollection/37518">OARSI 2024 World Congress</a>, the null findings of the <a href="https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06715-w">DICKENS study</a> and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640106/">ARTHROL trial</a> were presented alongside a reappraisal of the possible role of botulinum toxin.<br/><br/></p> <h2>DICKENS Study of Diacerein</h2> <p>“The role of diacerein in the treatment of OA is controversial,” acknowledged <a href="https://discover.utas.edu.au/Dawn.Aitken">Dawn Aitken</a>, PhD, associate professor at the University of Tasmania in Hobart, Tasmania, Australia. “There are only a few acceptable quality trials to date, and the results are inconsistent,” Dr. Aitken added.</p> <p>Indeed, a <a href="https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005117.pub3/full">Cochrane review performed in 2014</a> had concluded that there was “low-quality evidence that diacerein had a small beneficial effect on pain,” she said. The reported overall effect size on a 100-mm visual analog scale, based on a meta-analysis of 10 trials, has been just −8.65 mm, equating to just a 9% pain reduction.[[{"fid":"195552","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Dawn Aitken, University of Tasmania in Hobart, Tasmania, Australia","field_file_image_credit[und][0][value]":"Bruce Jancin/MDedge News","field_file_image_caption[und][0][value]":"Dr. Dawn Aitken"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]<br/><br/>At the time the DICKENS study was conceived, diacerein was recommended by a number of international guidelines for the management of hip and knee OA, although further, higher-quality studies were needed.<br/><br/>Diacerein blocks interleukin-1 beta, which is one of the key inflammatory markers of OA, so Dr. Aitken and collaborators postulated that perhaps it would work better if used in patients with an inflammatory phenotype.<br/><br/>They set about to test their hypothesis by recruiting 260 individuals with knee OA and MRI-detected effusion synovitis. The participants were then randomly allocated to treatment with either diacerein or a matching placebo for 24 weeks.<br/><br/>Individuals in the diacerein group were treated with an oral dose of 50 mg once daily for the first 2 weeks. If tolerated, the dose was increased to 50 mg twice daily.<br/><br/>No significant improvement in the primary endpoint of knee pain was seen comparing diacerein with placebo, with mean values of 53.2 mm and 56.4 mm, respectively, at 24 weeks using a 0-100 mm visual analog scale where 0 represented no pain and 100 represented the worst pain. It followed that there was no significant difference in the change from baseline to week 24 (−19.9 mm vs −18.6 mm; <em>P</em> = .77).<br/><br/>There was also no difference in the secondary endpoints, which included Western Ontario and McMaster Universities Arthritis Index pain, function, and stiffness. In fact, placebo-treated patients appeared to do better in terms of resolution of effusion synovitis as measured by a repeat MRI and quality of life, Dr. <a href="https://www.sciencedirect.com/science/article/abs/pii/S1063458424001201">Aitken reported</a>.<br/><br/>“These findings do not support the use of diacerein in treating patients with knee OA and effusion synovitis,” Dr. Aitken concluded.<br/><br/></p> <h2>ARTHROL Trial of Resveratrol</h2> <p>Similarly, <a href="https://www.sciencedirect.com/science/article/abs/pii/S1063458424001237">negative results were reported for resveratrol</a> from the ARTHROL trial, with 55% of the resveratrol- and 55% of placebo-treated individuals achieving a 20% reduction in knee pain intensity at 3 months. The actual change in knee pain from baseline to 3 months was −15.7 for resveratrol and −15.2 for placebo on a numerical rating scale that went from 0 (no pain) up to 100 (worst pain).</p> <p>Resveratrol is found naturally in grapes, peanuts, pine cones, and Chinese knotweed, and there is a growing body of evidence that it may have pleiotropic effects, said investigator <a href="https://t3s-1124.biomedicale.parisdescartes.fr/nos-publications-2/christelle-nguyen/">Christelle Nguyen</a>, PhD, MD, a professor of physical and rehabilitation medicine at Université Paris Cité, Paris, France.<br/><br/>It’s available in a powder form over the counter as a <a href="https://www.webmd.com/vitamins/ai/ingredientmono-307/resveratrol">treatment for multiple ailments</a>, but more recently, became available as an oral formulation. Dr. Nguyen and colleagues wanted to know if this would make a difference to OA knee pain when added to usual care.<br/><br/>A double-blind, multicenter, placebo-controlled randomized trial was therefore conducted that involved 142 people with knee OA who had been experiencing knee pain for at least 1 month. The participants were equally randomly allocated to receive either oral resveratrol given as two caplets of 20 mg twice daily for the first week, then once daily for a total of 6 months, or a matched placebo.<br/><br/>There was also no effect of resveratrol vs placebo on a host of secondary outcomes measured at 3 and 6 months.<br/><br/>The interpretation is that oral resveratrol may not be effective in this indication or have a biologic effect on the pain pathway, Dr. Nguyen said.[[{"fid":"301383","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Christelle Nguyen, professor of physical and rehabilitation medicine at Université Paris Cité, Paris, France","field_file_image_credit[und][0][value]":"Sara Freeman/Medscape Medical News","field_file_image_caption[und][0][value]":"Dr. Christelle Nguyen"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]<br/><br/>“Our findings do not support the use of [trans-resveratrol] supplementation in this patented formulation for reducing knee pain in adults with painful knee OA,” she concluded.<br/><br/></p> <h2>Botulinum Toxin: Over But Not Out?</h2> <p>Dr. Nguyen <a href="https://www.sciencedirect.com/science/article/abs/pii/S1063458424009075">separately reported data</a> from a new systematic review and meta-analysis on the use of intra-articular (IA) botulinum toxin type A (BoNT-A) for knee OA pain.</p> <p>Seven of the 14 randomized controlled trials included in the meta-analysis had looked specifically at knee OA outcomes in the short, intermediate, and long term.<br/><br/>Results showed a nonsignificant trend favoring BoNT-A use, with the standard mean difference in pain of 0.35 (−0.82; 0.12), −0.27 (−0.61; 0.08), and −0.43 (−1.12; 0.26) for short-, intermediate-, and long-term use, respectively.<br/><br/>In contrast, pain reductions were seen with BoNT-A in three trials that included people with OA of the shoulder or base of the thumb. This begs the question as to whether botulinum toxin may still have a role to play, Dr. Nguyen said in an interview.<br/><br/>“It seems like there may be a positive effect for the shoulder joint and base of the thumb,” she told this news organization.<br/><br/>“So, basically, we found differences between large and small to intermediate joints,” Dr. Nguyen added. “It questions the dilution of botulinum toxin into the joint. If it’s a big joint, maybe the dilution is too high,” she suggested.<br/><br/>This hypothesis will be tested in the upcoming RHIBOT II trial that will begin recruitment later this year. This is a follow-on from the RHIBOT trial that <a href="https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(22)00129-1/abstract">was published</a> in <em>The Lancet Rheumatology</em> 2 years ago.<br/><br/>Meanwhile, the use of botulinum toxin is off-label, Dr. Nguyen said. “We use it in our clinics only when first-line treatment had failed for base of thumb OA.” It’s not offered as a stand-alone intervention, and the IA injections need to be given by someone with experience, she said.<br/><br/></p> <h2>Methodologically Sound Studies</h2> <p>Commenting on the studies, <a href="https://health.ucdavis.edu/musculoskeletalhealth/bios/lane.html">Nancy E. Lane</a>, MD, said: “There have been small botulinum studies before but not powered enough so that you could confirm or refute hypotheses.”</p> <p>Dr. Lane, endowed professor of medicine, rheumatology, and aging research and director for the Center for Musculoskeletal Health at the University of California Davis School of Medicine, Sacramento, California, added: “Similarly for resveratrol, there have been lots of studies.”<br/><br/>Moreover, Dr. Lane observed that the studies were “really well-designed. They were well-powered. The subjects were selected in such a way that was good rigor in the methodologic design, and there were enough people in the studies so that you could really believe the results.”<br/><br/>The take-home is probably that these approaches do not work, Dr. Lane said, “at least when you apply them to moderate-severe knee OA patients, they don’t seem to make a difference.”<br/><br/>The congress was sponsored by the Osteoarthritis Research Society International.<br/><br/>The DICKENS study of diacerein was an investigator-initiated trial that was funded by the National Health and Medical Research Council of Australia. TRB Chemedica International S.A. provided diacerein free of charge for the trial but was not involved in the implementation or data analysis. Dr. Aitken had no conflicts of interest to disclose.<br/><br/>The ARTHROL trial of oral resveratrol was funded by the French Ministry of Health and Solidarity (Ministré des Solidarités et de la Santé). Yvery Laboratory provided the resveratrol caplet and matching placebo free of charge. Dr. Nguyen has financial relationships with Actelion, Grünenthal, Ipsen, Lilly, Meda, Merz, Novartis, Preciphar, Sandoz, Takeda, Thuasne, and UCB.<br/><br/>Dr. Lane had no relevant conflicts of interest to declare.</p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/diacerein-resveratrol-botulinum-toxin-disappoint-knee-2024a10008u8">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM OARSI 2024
EMA’s JAK Inhibitor Warning Criteria May Affect Up to 80% of Patients With Rheumatoid Arthritis
LIVERPOOL, ENGLAND — Four in five people with rheumatoid arthritis (RA) fall into “at risk” categories for the initiation of Janus kinase (JAK) inhibitors set by the European Medicines Agency (EMA), according to data from the long-running British Society for Rheumatology (BSR) Biologics Register in RA (BSRBR-RA).
The EMA decided in January 2023 to implement measures to reduce the risk for serious side effects with JAK inhibitors in the treatment of chronic inflammatory diseases. The EMA’s recommendations advise that JAK inhibitors “should be used in the following patients only if no suitable treatment alternatives are available: those aged 65 years or above, those at increased risk of major cardiovascular problems (such as heart attack or stroke), those who smoke or have done so for a long time in the past, and those at increased risk of cancer.” The guidance also says to use JAK inhibitors “with caution in patients with risk factors for blood clots in the lungs and in deep veins (venous thromboembolism [VTE]) ... [and that] the doses should be reduced in patient groups who are at risk of VTE, cancer, or major cardiovascular problems, where possible.”
To gauge the potential impact of the EMA’s decision, researchers analyzed BSRBR-RA data from 1341 individuals with RA who had started treatment with a JAK inhibitor before the agency issued its new recommendations. Among these individuals, 1075 (80.2%) met ≥ 1 EMA risk criterion. Half (54%) were current or past smokers, 44% had an increased risk for major cardiovascular events such as heart attack or stroke, 39% were 65 years or older, and 10% had an increased risk for cancer.
Nearly half (49%) of the study population who met ≥ 1 EMA risk criterion had received only one (31%) or no (18%) prior biologic disease-modifying antirheumatic drug (bDMARD), Zixing Tian, a PhD student at the University of Manchester in England, reported at the annual meeting of the British Society for Rheumatology. Of the remainder, 23% had received two prior bDMARDs, and 28% had previously received three or more bDMARDs.
The work suggests that majority of people who are currently being treated with JAK inhibitors would probably not be advised to start treatment with a JAK inhibitor today, the researchers suggested in their abstract.
Considerable Implications
There are potentially two ways of interpreting these data, suggested Ken Baker, BMBCh, PhD, senior clinical fellow and honorary consultant rheumatologist at Newcastle University in Newcastle upon Tyne, England.
“One is that rheumatologists starting these treatments are throwing caution to the wind and ignoring all guidance,” Dr. Baker said.
“The second is perhaps that the EMA guidance is difficult to implement in practice when it involves lots of the comorbidities and risk factors that commonly affect patients with rheumatoid arthritis.”
Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in England, also commented on the findings.
“We are going to exclude practically all of our patients if we follow EMA,” Dr. Emery said. “The implications are considerable because if someone has a DVT [deep vein thrombosis] or an MI [myocardial infarction], when we included them with a risk factor, what’s the implication if they choose to sue you?”
Moreover, the bigger question is what to do with all the people who are already established on a JAK inhibitor, Dr. Emery said. Should patients now switch off their medication? Doing so may well leave them with a period of inflammation that may be more harmful than continuing the JAK inhibitor, he suggested.
Were Cautions Warranted?
Like the US Food and Drug Administration, the EMA has concerns over the use of JAK inhibitors because of the drugs’ potential to increase the risk for serious side effects such as VTE, major adverse cardiovascular events, cancer, and all-cause mortality relative to tumor necrosis factor–alpha inhibitors.
Initially, the EMA issued cautions that only related to the use of tofacitinib (Xeljanz), which was the first JAK inhibitor to gain approval for RA and other chronic inflammatory diseases in Europe, but this expanded to include baricitinib (Olumiant) and most recently any member of the drug class, including abrocitinib (Cibinqo), filgotinib (Jyseleca), and upadacitinib (Rinvoq).
The EMA has done a responsible job of looking at the available data and issuing cautions to protect the populations of patients who may be exposed to these drugs, Peter C. Taylor, BMBCh, PhD, told this news organization. However, they are also severely restricting the populations of patients who can be treated with them. “It’s a complicated situation,” he said.
Dr. Taylor, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in England, was not only involved in some of the major JAK inhibitor clinical trials but also privy to the EMA’s recent deliberations as an observer during the process. He noted that the EMA originally considered restricting the use of the drug class in patients older than 50 years but settled upon age 65 years and older.
Shared Decision
“The issue for benefit and risk is there for any drug we use,” said Dr. Taylor, noting that there are over-the-counter drugs that can be “far more dangerous” than JAK inhibitors in terms of cardiovascular risk.
“In my opinion, the really key thing is to be able to communicate the issues with integrity, in a manner that the patient understands, to make sure that the risk is acceptable to them,” Dr. Taylor said.
It is all about optimizing treatment for an individual and proactively managing any other factors that may increase their personal risk for unwanted effects, Maya Buch, MBChB, PhD, professor of rheumatology and honorary consultant rheumatologist at the University of Manchester, said during a debate at the meeting.
“We still have unmet needs for our patient population. Patients aren’t achieving the goals and endpoints that we need,” Dr. Buch said.
“Don’t lose sight of the positive attributes that we’ve seen with JAK inhibitors,” she advised.
“We presume we know what the patient thinks when it comes to a matter of risk assessment, but it is always about tailoring treatment to that individual, and we are sometimes surprised in terms of what the patients want, even in the face of apparent higher risk,” Dr. Buch added.
Judicious Use
Iain McInnes, MBChB, PhD, observed during the same debate that it was “hard to argue that drugs are generally unsafe when they have already been approved. It’s also challenging to suggest they are not useful when they are being used.”
Dr. McInnes, honorary consultant rheumatologist and vice principal and head of the College of Medical Veterinary & Life Sciences at the University of Glasgow in Scotland, pointed out that the EMA warnings assume that all JAK inhibitors are the same, but is that really the case? This is complex biochemistry, and could newer JAK inhibitors have an improved safety profile?
“There is no free ride in the immune system, and we should bear that in mind,” Dr. McInnes said. “These drugs work ... but we are absolutely flitting along the boundaries of the safety/efficacy window.”
Dr. McInnes told this news organization that clinicians do have to be cautious.
“There’s a paradox in that the very age group that the regulators are now asking us to be cautious about prescribing is pushing JAK inhibitors later and later in the disease course,” he said. This is a time when people would already have other risks for cardiovascular and other events.
“Overall, if used within the regulatory advice, Janus kinase inhibitors are a really useful drug class.”
The BSRBR-RA is funded by a grant from the BSR. The BSR currently receives funding from AbbVie, Amgen, Celltrion, Eli Lilly, Pfizer, Samsung Bioepis, Sanofi, and Sandoz and in the past from Hospira, Merck Sharp & Dohme (MSD), Roche, SOBI, and UCB. This income finances a wholly separate contract between the BSR and the University of Manchester to host the BSRBR-RA. All decisions concerning study design, data capture, analyses, interpretation, and publication are made autonomously of any industrial contribution. Ms. Tian had no conflicts of interest to report. Dr. Emery disclosed ties to AbbVie, Bristol Myers Squibb (BMS), Eli Lilly, Pfizer, MSD, Novartis, Roche, Sandoz, Samsung, and UCB. Dr. Taylor disclosed ties to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB. Dr. Buch disclosed ties to Gilead, AbbVie, Arxx Therapeutics, Boehringer Ingelheim, CESAS Medical, Galapagos, Gilead, MediStreams, and Pfizer. Dr. McInnes disclosed ties to AbbVie, AstraZeneca, Boehringer Ingelheim, Compugen, Cabaletta Bio, Causeway, Dexterra, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, and UCB.
A version of this article appeared on Medscape.com .
LIVERPOOL, ENGLAND — Four in five people with rheumatoid arthritis (RA) fall into “at risk” categories for the initiation of Janus kinase (JAK) inhibitors set by the European Medicines Agency (EMA), according to data from the long-running British Society for Rheumatology (BSR) Biologics Register in RA (BSRBR-RA).
The EMA decided in January 2023 to implement measures to reduce the risk for serious side effects with JAK inhibitors in the treatment of chronic inflammatory diseases. The EMA’s recommendations advise that JAK inhibitors “should be used in the following patients only if no suitable treatment alternatives are available: those aged 65 years or above, those at increased risk of major cardiovascular problems (such as heart attack or stroke), those who smoke or have done so for a long time in the past, and those at increased risk of cancer.” The guidance also says to use JAK inhibitors “with caution in patients with risk factors for blood clots in the lungs and in deep veins (venous thromboembolism [VTE]) ... [and that] the doses should be reduced in patient groups who are at risk of VTE, cancer, or major cardiovascular problems, where possible.”
To gauge the potential impact of the EMA’s decision, researchers analyzed BSRBR-RA data from 1341 individuals with RA who had started treatment with a JAK inhibitor before the agency issued its new recommendations. Among these individuals, 1075 (80.2%) met ≥ 1 EMA risk criterion. Half (54%) were current or past smokers, 44% had an increased risk for major cardiovascular events such as heart attack or stroke, 39% were 65 years or older, and 10% had an increased risk for cancer.
Nearly half (49%) of the study population who met ≥ 1 EMA risk criterion had received only one (31%) or no (18%) prior biologic disease-modifying antirheumatic drug (bDMARD), Zixing Tian, a PhD student at the University of Manchester in England, reported at the annual meeting of the British Society for Rheumatology. Of the remainder, 23% had received two prior bDMARDs, and 28% had previously received three or more bDMARDs.
The work suggests that majority of people who are currently being treated with JAK inhibitors would probably not be advised to start treatment with a JAK inhibitor today, the researchers suggested in their abstract.
Considerable Implications
There are potentially two ways of interpreting these data, suggested Ken Baker, BMBCh, PhD, senior clinical fellow and honorary consultant rheumatologist at Newcastle University in Newcastle upon Tyne, England.
“One is that rheumatologists starting these treatments are throwing caution to the wind and ignoring all guidance,” Dr. Baker said.
“The second is perhaps that the EMA guidance is difficult to implement in practice when it involves lots of the comorbidities and risk factors that commonly affect patients with rheumatoid arthritis.”
Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in England, also commented on the findings.
“We are going to exclude practically all of our patients if we follow EMA,” Dr. Emery said. “The implications are considerable because if someone has a DVT [deep vein thrombosis] or an MI [myocardial infarction], when we included them with a risk factor, what’s the implication if they choose to sue you?”
Moreover, the bigger question is what to do with all the people who are already established on a JAK inhibitor, Dr. Emery said. Should patients now switch off their medication? Doing so may well leave them with a period of inflammation that may be more harmful than continuing the JAK inhibitor, he suggested.
Were Cautions Warranted?
Like the US Food and Drug Administration, the EMA has concerns over the use of JAK inhibitors because of the drugs’ potential to increase the risk for serious side effects such as VTE, major adverse cardiovascular events, cancer, and all-cause mortality relative to tumor necrosis factor–alpha inhibitors.
Initially, the EMA issued cautions that only related to the use of tofacitinib (Xeljanz), which was the first JAK inhibitor to gain approval for RA and other chronic inflammatory diseases in Europe, but this expanded to include baricitinib (Olumiant) and most recently any member of the drug class, including abrocitinib (Cibinqo), filgotinib (Jyseleca), and upadacitinib (Rinvoq).
The EMA has done a responsible job of looking at the available data and issuing cautions to protect the populations of patients who may be exposed to these drugs, Peter C. Taylor, BMBCh, PhD, told this news organization. However, they are also severely restricting the populations of patients who can be treated with them. “It’s a complicated situation,” he said.
Dr. Taylor, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in England, was not only involved in some of the major JAK inhibitor clinical trials but also privy to the EMA’s recent deliberations as an observer during the process. He noted that the EMA originally considered restricting the use of the drug class in patients older than 50 years but settled upon age 65 years and older.
Shared Decision
“The issue for benefit and risk is there for any drug we use,” said Dr. Taylor, noting that there are over-the-counter drugs that can be “far more dangerous” than JAK inhibitors in terms of cardiovascular risk.
“In my opinion, the really key thing is to be able to communicate the issues with integrity, in a manner that the patient understands, to make sure that the risk is acceptable to them,” Dr. Taylor said.
It is all about optimizing treatment for an individual and proactively managing any other factors that may increase their personal risk for unwanted effects, Maya Buch, MBChB, PhD, professor of rheumatology and honorary consultant rheumatologist at the University of Manchester, said during a debate at the meeting.
“We still have unmet needs for our patient population. Patients aren’t achieving the goals and endpoints that we need,” Dr. Buch said.
“Don’t lose sight of the positive attributes that we’ve seen with JAK inhibitors,” she advised.
“We presume we know what the patient thinks when it comes to a matter of risk assessment, but it is always about tailoring treatment to that individual, and we are sometimes surprised in terms of what the patients want, even in the face of apparent higher risk,” Dr. Buch added.
Judicious Use
Iain McInnes, MBChB, PhD, observed during the same debate that it was “hard to argue that drugs are generally unsafe when they have already been approved. It’s also challenging to suggest they are not useful when they are being used.”
Dr. McInnes, honorary consultant rheumatologist and vice principal and head of the College of Medical Veterinary & Life Sciences at the University of Glasgow in Scotland, pointed out that the EMA warnings assume that all JAK inhibitors are the same, but is that really the case? This is complex biochemistry, and could newer JAK inhibitors have an improved safety profile?
“There is no free ride in the immune system, and we should bear that in mind,” Dr. McInnes said. “These drugs work ... but we are absolutely flitting along the boundaries of the safety/efficacy window.”
Dr. McInnes told this news organization that clinicians do have to be cautious.
“There’s a paradox in that the very age group that the regulators are now asking us to be cautious about prescribing is pushing JAK inhibitors later and later in the disease course,” he said. This is a time when people would already have other risks for cardiovascular and other events.
“Overall, if used within the regulatory advice, Janus kinase inhibitors are a really useful drug class.”
The BSRBR-RA is funded by a grant from the BSR. The BSR currently receives funding from AbbVie, Amgen, Celltrion, Eli Lilly, Pfizer, Samsung Bioepis, Sanofi, and Sandoz and in the past from Hospira, Merck Sharp & Dohme (MSD), Roche, SOBI, and UCB. This income finances a wholly separate contract between the BSR and the University of Manchester to host the BSRBR-RA. All decisions concerning study design, data capture, analyses, interpretation, and publication are made autonomously of any industrial contribution. Ms. Tian had no conflicts of interest to report. Dr. Emery disclosed ties to AbbVie, Bristol Myers Squibb (BMS), Eli Lilly, Pfizer, MSD, Novartis, Roche, Sandoz, Samsung, and UCB. Dr. Taylor disclosed ties to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB. Dr. Buch disclosed ties to Gilead, AbbVie, Arxx Therapeutics, Boehringer Ingelheim, CESAS Medical, Galapagos, Gilead, MediStreams, and Pfizer. Dr. McInnes disclosed ties to AbbVie, AstraZeneca, Boehringer Ingelheim, Compugen, Cabaletta Bio, Causeway, Dexterra, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, and UCB.
A version of this article appeared on Medscape.com .
LIVERPOOL, ENGLAND — Four in five people with rheumatoid arthritis (RA) fall into “at risk” categories for the initiation of Janus kinase (JAK) inhibitors set by the European Medicines Agency (EMA), according to data from the long-running British Society for Rheumatology (BSR) Biologics Register in RA (BSRBR-RA).
The EMA decided in January 2023 to implement measures to reduce the risk for serious side effects with JAK inhibitors in the treatment of chronic inflammatory diseases. The EMA’s recommendations advise that JAK inhibitors “should be used in the following patients only if no suitable treatment alternatives are available: those aged 65 years or above, those at increased risk of major cardiovascular problems (such as heart attack or stroke), those who smoke or have done so for a long time in the past, and those at increased risk of cancer.” The guidance also says to use JAK inhibitors “with caution in patients with risk factors for blood clots in the lungs and in deep veins (venous thromboembolism [VTE]) ... [and that] the doses should be reduced in patient groups who are at risk of VTE, cancer, or major cardiovascular problems, where possible.”
To gauge the potential impact of the EMA’s decision, researchers analyzed BSRBR-RA data from 1341 individuals with RA who had started treatment with a JAK inhibitor before the agency issued its new recommendations. Among these individuals, 1075 (80.2%) met ≥ 1 EMA risk criterion. Half (54%) were current or past smokers, 44% had an increased risk for major cardiovascular events such as heart attack or stroke, 39% were 65 years or older, and 10% had an increased risk for cancer.
Nearly half (49%) of the study population who met ≥ 1 EMA risk criterion had received only one (31%) or no (18%) prior biologic disease-modifying antirheumatic drug (bDMARD), Zixing Tian, a PhD student at the University of Manchester in England, reported at the annual meeting of the British Society for Rheumatology. Of the remainder, 23% had received two prior bDMARDs, and 28% had previously received three or more bDMARDs.
The work suggests that majority of people who are currently being treated with JAK inhibitors would probably not be advised to start treatment with a JAK inhibitor today, the researchers suggested in their abstract.
Considerable Implications
There are potentially two ways of interpreting these data, suggested Ken Baker, BMBCh, PhD, senior clinical fellow and honorary consultant rheumatologist at Newcastle University in Newcastle upon Tyne, England.
“One is that rheumatologists starting these treatments are throwing caution to the wind and ignoring all guidance,” Dr. Baker said.
“The second is perhaps that the EMA guidance is difficult to implement in practice when it involves lots of the comorbidities and risk factors that commonly affect patients with rheumatoid arthritis.”
Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in England, also commented on the findings.
“We are going to exclude practically all of our patients if we follow EMA,” Dr. Emery said. “The implications are considerable because if someone has a DVT [deep vein thrombosis] or an MI [myocardial infarction], when we included them with a risk factor, what’s the implication if they choose to sue you?”
Moreover, the bigger question is what to do with all the people who are already established on a JAK inhibitor, Dr. Emery said. Should patients now switch off their medication? Doing so may well leave them with a period of inflammation that may be more harmful than continuing the JAK inhibitor, he suggested.
Were Cautions Warranted?
Like the US Food and Drug Administration, the EMA has concerns over the use of JAK inhibitors because of the drugs’ potential to increase the risk for serious side effects such as VTE, major adverse cardiovascular events, cancer, and all-cause mortality relative to tumor necrosis factor–alpha inhibitors.
Initially, the EMA issued cautions that only related to the use of tofacitinib (Xeljanz), which was the first JAK inhibitor to gain approval for RA and other chronic inflammatory diseases in Europe, but this expanded to include baricitinib (Olumiant) and most recently any member of the drug class, including abrocitinib (Cibinqo), filgotinib (Jyseleca), and upadacitinib (Rinvoq).
The EMA has done a responsible job of looking at the available data and issuing cautions to protect the populations of patients who may be exposed to these drugs, Peter C. Taylor, BMBCh, PhD, told this news organization. However, they are also severely restricting the populations of patients who can be treated with them. “It’s a complicated situation,” he said.
Dr. Taylor, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in England, was not only involved in some of the major JAK inhibitor clinical trials but also privy to the EMA’s recent deliberations as an observer during the process. He noted that the EMA originally considered restricting the use of the drug class in patients older than 50 years but settled upon age 65 years and older.
Shared Decision
“The issue for benefit and risk is there for any drug we use,” said Dr. Taylor, noting that there are over-the-counter drugs that can be “far more dangerous” than JAK inhibitors in terms of cardiovascular risk.
“In my opinion, the really key thing is to be able to communicate the issues with integrity, in a manner that the patient understands, to make sure that the risk is acceptable to them,” Dr. Taylor said.
It is all about optimizing treatment for an individual and proactively managing any other factors that may increase their personal risk for unwanted effects, Maya Buch, MBChB, PhD, professor of rheumatology and honorary consultant rheumatologist at the University of Manchester, said during a debate at the meeting.
“We still have unmet needs for our patient population. Patients aren’t achieving the goals and endpoints that we need,” Dr. Buch said.
“Don’t lose sight of the positive attributes that we’ve seen with JAK inhibitors,” she advised.
“We presume we know what the patient thinks when it comes to a matter of risk assessment, but it is always about tailoring treatment to that individual, and we are sometimes surprised in terms of what the patients want, even in the face of apparent higher risk,” Dr. Buch added.
Judicious Use
Iain McInnes, MBChB, PhD, observed during the same debate that it was “hard to argue that drugs are generally unsafe when they have already been approved. It’s also challenging to suggest they are not useful when they are being used.”
Dr. McInnes, honorary consultant rheumatologist and vice principal and head of the College of Medical Veterinary & Life Sciences at the University of Glasgow in Scotland, pointed out that the EMA warnings assume that all JAK inhibitors are the same, but is that really the case? This is complex biochemistry, and could newer JAK inhibitors have an improved safety profile?
“There is no free ride in the immune system, and we should bear that in mind,” Dr. McInnes said. “These drugs work ... but we are absolutely flitting along the boundaries of the safety/efficacy window.”
Dr. McInnes told this news organization that clinicians do have to be cautious.
“There’s a paradox in that the very age group that the regulators are now asking us to be cautious about prescribing is pushing JAK inhibitors later and later in the disease course,” he said. This is a time when people would already have other risks for cardiovascular and other events.
“Overall, if used within the regulatory advice, Janus kinase inhibitors are a really useful drug class.”
The BSRBR-RA is funded by a grant from the BSR. The BSR currently receives funding from AbbVie, Amgen, Celltrion, Eli Lilly, Pfizer, Samsung Bioepis, Sanofi, and Sandoz and in the past from Hospira, Merck Sharp & Dohme (MSD), Roche, SOBI, and UCB. This income finances a wholly separate contract between the BSR and the University of Manchester to host the BSRBR-RA. All decisions concerning study design, data capture, analyses, interpretation, and publication are made autonomously of any industrial contribution. Ms. Tian had no conflicts of interest to report. Dr. Emery disclosed ties to AbbVie, Bristol Myers Squibb (BMS), Eli Lilly, Pfizer, MSD, Novartis, Roche, Sandoz, Samsung, and UCB. Dr. Taylor disclosed ties to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB. Dr. Buch disclosed ties to Gilead, AbbVie, Arxx Therapeutics, Boehringer Ingelheim, CESAS Medical, Galapagos, Gilead, MediStreams, and Pfizer. Dr. McInnes disclosed ties to AbbVie, AstraZeneca, Boehringer Ingelheim, Compugen, Cabaletta Bio, Causeway, Dexterra, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, and UCB.
A version of this article appeared on Medscape.com .
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>LIVERPOOL, ENGLAND — Four in five people with rheumatoid arthritis (RA) fall into “at risk” categories for the initiation of Janus kinase (JAK) inhibitors set b</metaDescription> <articlePDF/> <teaserImage>301382</teaserImage> <teaser>Recent regulatory warnings could mean that four in five patients with RA in Europe may not be prescribed JAK inhibitors unless there is no other alternative.</teaser> <title>EMA’s JAK Inhibitor Warning Criteria May Affect Up to 80% of Patients With Rheumatoid Arthritis</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>21</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">289</term> <term>290</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012906.jpg</altRep> <description role="drol:caption">Zixing Tian</description> <description role="drol:credit">Sara Freeman/Medscape Medical News</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24011147.jpg</altRep> <description role="drol:caption">Dr. Paul Emery</description> <description role="drol:credit"/> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24006d55.jpg</altRep> <description role="drol:caption">Dr. Peter C. Taylor</description> <description role="drol:credit"/> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012905.jpg</altRep> <description role="drol:caption">Dr. Maya Buch (left) and Dr. Iain McInnes</description> <description role="drol:credit">Sara Freeman/Medscape Medical News</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>EMA’s JAK Inhibitor Warning Criteria May Affect Up to 80% of Patients With Rheumatoid Arthritis</title> <deck/> </itemMeta> <itemContent> <p>LIVERPOOL, ENGLAND — Four in five people with rheumatoid arthritis (RA) fall into “at risk” categories for the initiation of Janus kinase (JAK) inhibitors set by the European Medicines Agency (EMA), according to data from the long-running British Society for Rheumatology (BSR) Biologics Register in RA (BSRBR-RA).</p> <p>The EMA <span class="Hyperlink"><a href="https://www.ema.europa.eu/en/medicines/human/referrals/janus-kinase-inhibitors-jaki">decided in January 2023</a></span> to implement measures to reduce the risk for serious side effects with JAK inhibitors in the treatment of chronic inflammatory diseases. The EMA’s recommendations advise that JAK inhibitors “should be used in the following patients only if no suitable treatment alternatives are available: those aged 65 years or above, those at increased risk of major cardiovascular problems (such as heart attack or stroke), those who smoke or have done so for a long time in the past, and those at increased risk of cancer.” The guidance also says to use JAK inhibitors “with caution in patients with risk factors for blood clots in the lungs and in deep veins (venous thromboembolism [VTE]) ... [and that] the doses should be reduced in patient groups who are at risk of VTE, cancer, or major cardiovascular problems, where possible.”<br/><br/>To gauge the potential impact of the EMA’s decision, researchers analyzed BSRBR-RA data from 1341 individuals with RA who had started treatment with a JAK inhibitor before the agency issued its new recommendations. Among these individuals, 1075 (80.2%) met ≥ 1 EMA risk criterion. Half (54%) were current or past smokers, 44% had an increased risk for major cardiovascular events such as heart attack or stroke, 39% were 65 years or older, and 10% had an increased risk for cancer.<br/><br/>Nearly half (49%) of the study population who met ≥ 1 EMA risk criterion had received only one (31%) or no (18%) prior biologic disease-modifying antirheumatic drug (bDMARD), Zixing Tian, a PhD student at the University of Manchester in England, reported at the <a href="https://www.medscape.com/viewcollection/37509"> annual meeting</a> of the British Society for Rheumatology. Of the remainder, 23% had received two prior bDMARDs, and 28% had previously received three or more bDMARDs.[[{"fid":"301382","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Zixing Tian, a PhD student at The University of Manchester in England","field_file_image_credit[und][0][value]":"Sara Freeman/Medscape Medical News","field_file_image_caption[und][0][value]":"Zixing Tian"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]<br/><br/>The work suggests that majority of people who are currently being treated with JAK inhibitors would probably not be advised to start treatment with a JAK inhibitor today, the researchers suggested in <a href="https://doi.org/10.1093/rheumatology/keae163.005">their abstract</a>.<br/><br/></p> <h2>Considerable Implications</h2> <p>There are potentially two ways of interpreting these data, suggested <a href="https://www.ncl.ac.uk/medical-sciences/people/profile/kennethbaker.html">Ken Baker</a>, BMBCh, PhD, senior clinical fellow and honorary consultant rheumatologist at Newcastle University in Newcastle upon Tyne, England.</p> <p>“One is that rheumatologists starting these treatments are throwing caution to the wind and ignoring all guidance,” Dr. Baker said.<br/><br/>“The second is perhaps that the EMA guidance is difficult to implement in practice when it involves lots of the comorbidities and risk factors that commonly affect patients with rheumatoid arthritis.”<br/><br/><a href="https://medicinehealth.leeds.ac.uk/medicine/staff/308/professor-paul-emery">Paul Emery</a>, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in England, also commented on the findings.[[{"fid":"288998","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Paul Emery, professor of rheumatology and director of the University of Leeds (England) Musculoskeletal Biomedical Research Centre","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Paul Emery"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]<br/><br/>“We are going to exclude practically all of our patients if we follow EMA,” Dr. Emery said. “The implications are considerable because if someone has a DVT [deep vein thrombosis] or an MI [myocardial infarction], when we included them with a risk factor, what’s the implication if they choose to sue you?”<br/><br/>Moreover, the bigger question is what to do with all the people who are already established on a JAK inhibitor, Dr. Emery said. Should patients now switch off their medication? Doing so may well leave them with a period of inflammation that may be more harmful than continuing the JAK inhibitor, he suggested.<br/><br/></p> <h2>Were Cautions Warranted?</h2> <p>Like the US Food and Drug Administration, the EMA has concerns over the use of JAK inhibitors because of the drugs’ potential to increase the risk for serious side effects such as VTE, major adverse cardiovascular events, cancer, and all-cause mortality relative to tumor necrosis factor–alpha inhibitors.</p> <p>Initially, the EMA issued cautions that only related to the use of tofacitinib (Xeljanz), which was the first JAK inhibitor to gain approval for RA and other chronic inflammatory diseases in Europe, but this expanded to include baricitinib (Olumiant) and most recently any member of the drug class, including abrocitinib (Cibinqo), filgotinib (Jyseleca), and upadacitinib (Rinvoq).<br/><br/>The EMA has done a responsible job of looking at the available data and issuing cautions to protect the populations of patients who may be exposed to these drugs, <a href="https://www.ndorms.ox.ac.uk/team/peter-taylor">Peter C. Taylor</a>, BMBCh, PhD, told this news organization. However, they are also severely restricting the populations of patients who can be treated with them. “It’s a complicated situation,” he said.[[{"fid":"190004","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Peter C. Taylor, University of Oxford","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Peter C. Taylor"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]<br/><br/>Dr. Taylor, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in England, was not only involved in some of the major JAK inhibitor clinical trials but also privy to the EMA’s recent deliberations as an observer during the process. He noted that the EMA originally considered restricting the use of the drug class in patients older than 50 years but settled upon age 65 years and older.<br/><br/></p> <h2>Shared Decision</h2> <p>“The issue for benefit and risk is there for any drug we use,” said Dr. Taylor, noting that there are over-the-counter drugs that can be “far more dangerous” than JAK inhibitors in terms of cardiovascular risk.</p> <p>“In my opinion, the really key thing is to be able to communicate the issues with integrity, in a manner that the patient understands, to make sure that the risk is acceptable to them,” Dr. Taylor said.<br/><br/>It is all about optimizing treatment for an individual and proactively managing any other factors that may increase their personal risk for unwanted effects, <a href="https://personalpages.manchester.ac.uk/advanced.php?dn=cn%3DMaya+Buch%2Bumanroleid%3D737952%2Cou%3DDivision+of+Musculoskeletal+%26+Dermatological+Sciences%2Cou%3DSchool+of+Biological+Sciences%2Cou%3DFaculty+of+Biology%5C%2C+Medicine+and+Health%2Cou%3DPeople%2Co%3DUniversity+of+Manchester%2Cc%3DGB&employeeType=STAFF&action=read&form_input=Submit">Maya Buch</a>, MBChB, PhD, professor of rheumatology and honorary consultant rheumatologist at the University of Manchester, said during a debate at the meeting.<br/><br/>“We still have unmet needs for our patient population. Patients aren’t achieving the goals and endpoints that we need,” Dr. Buch said.<br/><br/>“Don’t lose sight of the positive attributes that we’ve seen with JAK inhibitors,” she advised.<br/><br/>“We presume we know what the patient thinks when it comes to a matter of risk assessment, but it is always about tailoring treatment to that individual, and we are sometimes surprised in terms of what the patients want, even in the face of apparent higher risk,” Dr. Buch added.<br/><br/></p> <h2>Judicious Use</h2> <p><a href="https://www.gla.ac.uk/research/beacons/precisionmedicine/professoriainmcinnes/">Iain McInnes</a>, MBChB, PhD, observed during the same debate that it was “hard to argue that drugs are generally unsafe when they have already been approved. It’s also challenging to suggest they are not useful when they are being used.”[[{"fid":"301381","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Maya Buch (left) and Dr. Iain McInnes","field_file_image_credit[und][0][value]":"Sara Freeman/Medscape Medical News","field_file_image_caption[und][0][value]":"Dr. Maya Buch (left) and Dr. Iain McInnes"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]</p> <p>Dr. McInnes, honorary consultant rheumatologist and vice principal and head of the College of Medical Veterinary & Life Sciences at the University of Glasgow in Scotland, pointed out that the EMA warnings assume that all JAK inhibitors are the same, but is that really the case? This is complex biochemistry, and could newer JAK inhibitors have an improved safety profile?<br/><br/>“There is no free ride in the immune system, and we should bear that in mind,” Dr. McInnes said. “These drugs work ... but we are absolutely flitting along the boundaries of the safety/efficacy window.”<br/><br/>Dr. McInnes told this news organization that clinicians do have to be cautious.<br/><br/>“There’s a paradox in that the very age group that the regulators are now asking us to be cautious about prescribing is pushing JAK inhibitors later and later in the disease course,” he said. This is a time when people would already have other risks for cardiovascular and other events.<br/><br/>“Overall, if used within the regulatory advice, Janus kinase inhibitors are a really useful drug class.”<br/><br/>The BSRBR-RA is funded by a grant from the BSR. The BSR currently receives funding from AbbVie, Amgen, Celltrion, Eli Lilly, Pfizer, Samsung Bioepis, Sanofi, and Sandoz and in the past from Hospira, Merck Sharp & Dohme (MSD), Roche, SOBI, and UCB. This income finances a wholly separate contract between the BSR and the University of Manchester to host the BSRBR-RA. All decisions concerning study design, data capture, analyses, interpretation, and publication are made autonomously of any industrial contribution. Ms. Tian had no conflicts of interest to report. Dr. Emery disclosed ties to AbbVie, Bristol Myers Squibb (BMS), Eli Lilly, Pfizer, MSD, Novartis, Roche, Sandoz, Samsung, and UCB. Dr. Taylor disclosed ties to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB. Dr. Buch disclosed ties to Gilead, AbbVie, Arxx Therapeutics, Boehringer Ingelheim, CESAS Medical, Galapagos, Gilead, MediStreams, and Pfizer. Dr. McInnes disclosed ties to AbbVie, AstraZeneca, Boehringer Ingelheim, Compugen, Cabaletta Bio, Causeway, Dexterra, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, and UCB.</p> <p> <em> <span class="Emphasis">A version of this article appeared on </span> <span class="Hyperlink"> <a href="https://www.medscape.com/viewarticle/most-patients-rheumatoid-arthritis-meet-european-medicines-2024a10008kq">Medscape.com</a> </span> <span class="Emphasis">.</span> </em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM BSR 2024
