Rheumatology News

VIENNA — An intervention consisting of a plant-based diet, exercise, and sleep and stress advice improved pain, stiffness, and physical function in people with knee and/or hip osteoarthritis (OA) and metabolic syndrome, while in patients with rheumatoid arthritis (RA), disease activity improved significantly, and medication use was reduced.

At the annual European Congress of Rheumatology, Carlijn Wagenaar, MD, a PhD candidate in Clinical Immunology and Rheumatology at Amsterdam University Medical Center, presented 2-year extension study results for OA and RA and an overview of the possible biological mechanisms underpinning the plant-based intervention in RA.

“At 2 years, RA patients on the PFJ [Plants for Joints] intervention resulted in a significant improvement in disease activity of RA, and these outcomes were maintained 2 years after program end,” Dr. Wagenaar reported.

“Some initial improvements in body composition and metabolic outcomes were also maintained at the end of the 2-year extension phase, and there was a net decrease in antirheumatic medication use,” she continued.

In the patients with OA, Dr. Wagenaar said the PFJ intervention improved pain, stiffness, and physical function in people with knee and/or hip OA and metabolic syndrome. “In the 2-year extension study, these effects were maintained, and we saw lasting body composition changes and a decrease in cholesterol-lowering medications. There was also high acceptability of the program; the study shows long-term maintenance of clinically relevant effects.”
 

Significant Improvement in OA Pain, Stiffness, Physical Function

In the OA randomized controlled trial, 64 people with hip and/or knee OA and metabolic syndrome were randomized to the PFJ intervention or usual care (waitlist control group). A total of 62 participants (including those in the control group previously) entered the long-term effectiveness study, and 44 had 2 years of follow-up data for analysis. Twenty participants dropped out, with most being unreachable or too busy.

“The PFJ program is a theoretical and practical program where people learn about and follow a whole food, plant-based diet, and receive advice on sleep and stress management and exercise,” said Dr. Wagenaar.

The program lasted 16 weeks with group sessions of 6-12 participants. The diet was a plant-based version of the Dutch dietary guidelines with a focus on unprocessed food. It was rich in whole grains, legumes, nuts, seeds, fruit, and vegetables, but without calorie restrictions and participants had one-to-one contact with a dietitian. The exercise advice followed the Dutch exercise guidelines, which advise 150 minutes of moderate to intense exercise per week, as well as twice-weekly muscle strength exercises, noted Dr. Wagenaar.

The 2-year follow-up study involved twice-yearly visits and six adherence-promoting webinars per year, as well as monthly newsletters. Researchers also monitored changes in medication intensity (classified as “increased,” “stable,” or “decreased/stopped”) between the start of the PFJ intervention and end of the 2-year extension study, and they were grouped into medications for pain, blood pressure, glucose, and cholesterol.

Participants were encouraged to try to avoid making changes to medication during the intervention phase, but they could do so during the 2-year extension study, said Dr. Wagenaar. In fact, the researchers actively monitored and quantified medication changes between the start of the PFJ intervention and end of the 2-year follow-up period.

Patients in the 16-week trial had an average age of 64 years, 84% were women, and their mean body mass index (BMI) was 33 kg/m². A total of 73% had knee OA and 78% hip OA, and their mean WOMAC score was 38.2, indicative of moderate to severe OA.

In participants who completed the 2-year extension study, the primary outcome (WOMAC score for mean stiffness and physical function) showed a significant improvement of −9.1 (95% CI, −12.8 to −5.3; P < .0001) compared with the start of the PFJ intervention.

“Looking at individual components of the WOMAC score — pain, stiffness, and physical function — we found these also all significantly improved at the end of the 2-year extension phase,” reported Dr. Wagenaar.

She added that after 2 years, there were significant improvements in weight loss (from 94.9 to 92.1 kg), BMI (from 33.3 to 32 kg/m²), and waist circumference (from 110 to 106.7 cm).

By the end of the trial and at 1 year of the extension study, there were significant improvements in A1c, fasting blood glucose, and low-density lipoprotein cholesterol, but at 2 years, these were no longer significant.

Regarding medications use, Dr. Wagenaar reported that, overall, there was no net change in use of pain, glucose-lowering, or hypertension medications, but 44% of patients using cholesterol-lowering medications were able to lower their dose or stop them.
 

Disease Activity Improvement and Medication Reduction in RA

Turning to the study of the intervention in patients with RA, 77 people (DAS28 ≥ 2.6 and ≤ 5.1, mild to moderate disease) were randomized to receive either the PFJ intervention in addition to usual care or only usual care (control group). Of these, 48 (62%) from both the intervention and control groups also completed the 2-year follow-up. The details of the PFJ intervention and the extension study for RA were the same as for the OA patient group.

Dr. Wagenaar commented on how they tried to individualize the exercise part of the program. “We noticed many of the RA patients asked too much of their body, while in contrast, those with OA were too hesitant,” she said. “We decided to focus on people’s own physical barriers, and we wanted to protect these. Sometimes, people needed to move more, and at other times, we had to tell people to slow down. Often, we advised people to move more by integrating exercise into their daily life.”

Similar to the OA study, patients were asked to try to avoid changing their medications in the 16-week study. “In the extension study, they were encouraged to reduce their medication in collaboration with their rheumatologist,” explained Wagenaar, who monitored any changes.

Differences were quantified according to medication groups comprising rheumatic medications, as well as pain, blood pressure, glucose-lowering, and cholesterol medications, and changes were categorized as increased, stable, or decreased/stopped.

Again, participants were mostly women (92%) with an average age of 55 years, BMI of 26 kg/m², and DAS28 of 3.85 at baseline. Dropout reasons were similar to those for OA, and over 85% of participants were on medications.

During the 16-week trial period, the DAS28 changed more in the intervention participants than in the controls, and after 2 years of follow-up, DAS28 was significantly lower than baseline with a mean difference of −0.9 (95% CI, −1.2 to −0.6; P < .0001).

“Comparing with the literature, the drop in DAS28 was similar to that seen with medication, so it’s a very significant reduction,” remarked Dr. Wagenaar.

Mean tender joint count dropped from 3 to 0, and general health components of the DAS28 improved significantly over the intervention and over the 2-year follow-up, whereas there was no significant difference in the already low erythrocyte sedimentation rate and swollen joint count compared with baseline. C-reactive protein (CRP) changed from 3.2 to 1.3 mg/L over the 2-year follow-up. High-density lipoprotein increased from 1.6 to 1.8 mmol/L.

A total of 44% of people using antirheumatic medication decreased or stopped them after the 2-year extension.

Dr. Wagenaar went on to say that focus group findings suggested that “participants were very enthusiastic about the program despite it largely involving lifestyle change, and this is reflected in our low dropout rates after the trial and 1-year extension [20% for OA and RA].” There were more dropouts in year 2 of the extension.

In an interview, Dr. Wagenaar explained why she felt the program had been so well received. “People in the program felt like they had more control over their disease, and they felt listened to.”
 

Mechanisms Underpinning PFJ

Dr. Wagenaar and colleagues also sought to determine the possible mechanisms underlying the clinical effects of the plant-based diet on RA. “With RA, we have the mucosal origins hypothesis, which suggests RA is triggered at the mucosal site [of the gut] in genetically predisposed individuals, and this consequently transfers to the synovial [fluid in] joints,” she said.

“On top of this, we know that fiber protects our gut barrier and therefore reduces inflammation. The PFJ intervention is a very high-fiber program, so our hypothesis is that it might help [strengthen] the barrier,” she explained.

Dr. Wagenaar and colleagues collected fecal samples from patients and measured the albumin and calprotectin in them, which are both indicators of the gut barrier function. The researchers analyzed metabolomic data and found that fecal albumin — considered a gut barrier integrity marker — decreased significantly in the intervention group. In patients with RA, this improvement corresponded with an improvement in DAS28, the researchers reported in a poster at the meeting.

“Patients who had the greatest improvement in their gut barrier function also showed the greatest improvement in the DAS28 score, suggestive of a possible link between gut barrier improvement and clinical effects.”

They did not identify any change in calprotectin, an inflammation marker, but Dr. Wagenaar said this might change later. “We found that in those on the intervention, at 4 months, the CRP wasn’t reduced, but 1 year later it was.”

The metabolite lenticin, a lentil intake biomarker considered protective against inflammation and osteoclastic differentiation, also increased. Tryptophan was also reduced in people on the PFJ intervention.

Fernando Estevez-Lopez, PhD, a sports scientist at Harvard T.H. Chan School of Public Health, Boston, who specializes in physical activity and behavioral change in rheumatology patients, co-moderated the session and remarked that, “In this study, they did a brilliant job with encouraging participants to follow the program. The design and methods were really good — the sample size was good, and they followed people up. Also, these researchers come from Reade [a medical research center in Amsterdam University Medical Center] where they are well known for applying their research findings to the clinic,” he said.

“In terms of physical activity, we really mean increasing the time spent moving, for example, gentle activity such as walking, or changing behaviors in people with OA and RA. We don’t want them to have more pain the next day.”

Dr. Wagenaar reported receiving a grant from ZonMw (The Netherlands Organization for Health Research and Development). She and colleagues hold shares in Plants for Health, a limited liability company. Dr. Estevez-Lopez reported having no relevant disclosures.
 

A version of this article appeared on Medscape.com.

VIENNA — An intervention consisting of a plant-based diet, exercise, and sleep and stress advice improved pain, stiffness, and physical function in people with knee and/or hip osteoarthritis (OA) and metabolic syndrome, while in patients with rheumatoid arthritis (RA), disease activity improved significantly, and medication use was reduced.

At the annual European Congress of Rheumatology, Carlijn Wagenaar, MD, a PhD candidate in Clinical Immunology and Rheumatology at Amsterdam University Medical Center, presented 2-year extension study results for OA and RA and an overview of the possible biological mechanisms underpinning the plant-based intervention in RA.

“At 2 years, RA patients on the PFJ [Plants for Joints] intervention resulted in a significant improvement in disease activity of RA, and these outcomes were maintained 2 years after program end,” Dr. Wagenaar reported.

“Some initial improvements in body composition and metabolic outcomes were also maintained at the end of the 2-year extension phase, and there was a net decrease in antirheumatic medication use,” she continued.

In the patients with OA, Dr. Wagenaar said the PFJ intervention improved pain, stiffness, and physical function in people with knee and/or hip OA and metabolic syndrome. “In the 2-year extension study, these effects were maintained, and we saw lasting body composition changes and a decrease in cholesterol-lowering medications. There was also high acceptability of the program; the study shows long-term maintenance of clinically relevant effects.”
 

Significant Improvement in OA Pain, Stiffness, Physical Function

In the OA randomized controlled trial, 64 people with hip and/or knee OA and metabolic syndrome were randomized to the PFJ intervention or usual care (waitlist control group). A total of 62 participants (including those in the control group previously) entered the long-term effectiveness study, and 44 had 2 years of follow-up data for analysis. Twenty participants dropped out, with most being unreachable or too busy.

“The PFJ program is a theoretical and practical program where people learn about and follow a whole food, plant-based diet, and receive advice on sleep and stress management and exercise,” said Dr. Wagenaar.

The program lasted 16 weeks with group sessions of 6-12 participants. The diet was a plant-based version of the Dutch dietary guidelines with a focus on unprocessed food. It was rich in whole grains, legumes, nuts, seeds, fruit, and vegetables, but without calorie restrictions and participants had one-to-one contact with a dietitian. The exercise advice followed the Dutch exercise guidelines, which advise 150 minutes of moderate to intense exercise per week, as well as twice-weekly muscle strength exercises, noted Dr. Wagenaar.

The 2-year follow-up study involved twice-yearly visits and six adherence-promoting webinars per year, as well as monthly newsletters. Researchers also monitored changes in medication intensity (classified as “increased,” “stable,” or “decreased/stopped”) between the start of the PFJ intervention and end of the 2-year extension study, and they were grouped into medications for pain, blood pressure, glucose, and cholesterol.

Participants were encouraged to try to avoid making changes to medication during the intervention phase, but they could do so during the 2-year extension study, said Dr. Wagenaar. In fact, the researchers actively monitored and quantified medication changes between the start of the PFJ intervention and end of the 2-year follow-up period.

Patients in the 16-week trial had an average age of 64 years, 84% were women, and their mean body mass index (BMI) was 33 kg/m². A total of 73% had knee OA and 78% hip OA, and their mean WOMAC score was 38.2, indicative of moderate to severe OA.

In participants who completed the 2-year extension study, the primary outcome (WOMAC score for mean stiffness and physical function) showed a significant improvement of −9.1 (95% CI, −12.8 to −5.3; P < .0001) compared with the start of the PFJ intervention.

“Looking at individual components of the WOMAC score — pain, stiffness, and physical function — we found these also all significantly improved at the end of the 2-year extension phase,” reported Dr. Wagenaar.

She added that after 2 years, there were significant improvements in weight loss (from 94.9 to 92.1 kg), BMI (from 33.3 to 32 kg/m²), and waist circumference (from 110 to 106.7 cm).

By the end of the trial and at 1 year of the extension study, there were significant improvements in A1c, fasting blood glucose, and low-density lipoprotein cholesterol, but at 2 years, these were no longer significant.

Regarding medications use, Dr. Wagenaar reported that, overall, there was no net change in use of pain, glucose-lowering, or hypertension medications, but 44% of patients using cholesterol-lowering medications were able to lower their dose or stop them.
 

Disease Activity Improvement and Medication Reduction in RA

Turning to the study of the intervention in patients with RA, 77 people (DAS28 ≥ 2.6 and ≤ 5.1, mild to moderate disease) were randomized to receive either the PFJ intervention in addition to usual care or only usual care (control group). Of these, 48 (62%) from both the intervention and control groups also completed the 2-year follow-up. The details of the PFJ intervention and the extension study for RA were the same as for the OA patient group.

Dr. Wagenaar commented on how they tried to individualize the exercise part of the program. “We noticed many of the RA patients asked too much of their body, while in contrast, those with OA were too hesitant,” she said. “We decided to focus on people’s own physical barriers, and we wanted to protect these. Sometimes, people needed to move more, and at other times, we had to tell people to slow down. Often, we advised people to move more by integrating exercise into their daily life.”

Similar to the OA study, patients were asked to try to avoid changing their medications in the 16-week study. “In the extension study, they were encouraged to reduce their medication in collaboration with their rheumatologist,” explained Wagenaar, who monitored any changes.

Differences were quantified according to medication groups comprising rheumatic medications, as well as pain, blood pressure, glucose-lowering, and cholesterol medications, and changes were categorized as increased, stable, or decreased/stopped.

Again, participants were mostly women (92%) with an average age of 55 years, BMI of 26 kg/m², and DAS28 of 3.85 at baseline. Dropout reasons were similar to those for OA, and over 85% of participants were on medications.

During the 16-week trial period, the DAS28 changed more in the intervention participants than in the controls, and after 2 years of follow-up, DAS28 was significantly lower than baseline with a mean difference of −0.9 (95% CI, −1.2 to −0.6; P < .0001).

“Comparing with the literature, the drop in DAS28 was similar to that seen with medication, so it’s a very significant reduction,” remarked Dr. Wagenaar.

Mean tender joint count dropped from 3 to 0, and general health components of the DAS28 improved significantly over the intervention and over the 2-year follow-up, whereas there was no significant difference in the already low erythrocyte sedimentation rate and swollen joint count compared with baseline. C-reactive protein (CRP) changed from 3.2 to 1.3 mg/L over the 2-year follow-up. High-density lipoprotein increased from 1.6 to 1.8 mmol/L.

A total of 44% of people using antirheumatic medication decreased or stopped them after the 2-year extension.

Dr. Wagenaar went on to say that focus group findings suggested that “participants were very enthusiastic about the program despite it largely involving lifestyle change, and this is reflected in our low dropout rates after the trial and 1-year extension [20% for OA and RA].” There were more dropouts in year 2 of the extension.

In an interview, Dr. Wagenaar explained why she felt the program had been so well received. “People in the program felt like they had more control over their disease, and they felt listened to.”
 

Mechanisms Underpinning PFJ

Dr. Wagenaar and colleagues also sought to determine the possible mechanisms underlying the clinical effects of the plant-based diet on RA. “With RA, we have the mucosal origins hypothesis, which suggests RA is triggered at the mucosal site [of the gut] in genetically predisposed individuals, and this consequently transfers to the synovial [fluid in] joints,” she said.

“On top of this, we know that fiber protects our gut barrier and therefore reduces inflammation. The PFJ intervention is a very high-fiber program, so our hypothesis is that it might help [strengthen] the barrier,” she explained.

Dr. Wagenaar and colleagues collected fecal samples from patients and measured the albumin and calprotectin in them, which are both indicators of the gut barrier function. The researchers analyzed metabolomic data and found that fecal albumin — considered a gut barrier integrity marker — decreased significantly in the intervention group. In patients with RA, this improvement corresponded with an improvement in DAS28, the researchers reported in a poster at the meeting.

“Patients who had the greatest improvement in their gut barrier function also showed the greatest improvement in the DAS28 score, suggestive of a possible link between gut barrier improvement and clinical effects.”

They did not identify any change in calprotectin, an inflammation marker, but Dr. Wagenaar said this might change later. “We found that in those on the intervention, at 4 months, the CRP wasn’t reduced, but 1 year later it was.”

The metabolite lenticin, a lentil intake biomarker considered protective against inflammation and osteoclastic differentiation, also increased. Tryptophan was also reduced in people on the PFJ intervention.

Fernando Estevez-Lopez, PhD, a sports scientist at Harvard T.H. Chan School of Public Health, Boston, who specializes in physical activity and behavioral change in rheumatology patients, co-moderated the session and remarked that, “In this study, they did a brilliant job with encouraging participants to follow the program. The design and methods were really good — the sample size was good, and they followed people up. Also, these researchers come from Reade [a medical research center in Amsterdam University Medical Center] where they are well known for applying their research findings to the clinic,” he said.

“In terms of physical activity, we really mean increasing the time spent moving, for example, gentle activity such as walking, or changing behaviors in people with OA and RA. We don’t want them to have more pain the next day.”

Dr. Wagenaar reported receiving a grant from ZonMw (The Netherlands Organization for Health Research and Development). She and colleagues hold shares in Plants for Health, a limited liability company. Dr. Estevez-Lopez reported having no relevant disclosures.
 

A version of this article appeared on Medscape.com.

VIENNA — An intervention consisting of a plant-based diet, exercise, and sleep and stress advice improved pain, stiffness, and physical function in people with knee and/or hip osteoarthritis (OA) and metabolic syndrome, while in patients with rheumatoid arthritis (RA), disease activity improved significantly, and medication use was reduced.

At the annual European Congress of Rheumatology, Carlijn Wagenaar, MD, a PhD candidate in Clinical Immunology and Rheumatology at Amsterdam University Medical Center, presented 2-year extension study results for OA and RA and an overview of the possible biological mechanisms underpinning the plant-based intervention in RA.

“At 2 years, RA patients on the PFJ [Plants for Joints] intervention resulted in a significant improvement in disease activity of RA, and these outcomes were maintained 2 years after program end,” Dr. Wagenaar reported.

“Some initial improvements in body composition and metabolic outcomes were also maintained at the end of the 2-year extension phase, and there was a net decrease in antirheumatic medication use,” she continued.

In the patients with OA, Dr. Wagenaar said the PFJ intervention improved pain, stiffness, and physical function in people with knee and/or hip OA and metabolic syndrome. “In the 2-year extension study, these effects were maintained, and we saw lasting body composition changes and a decrease in cholesterol-lowering medications. There was also high acceptability of the program; the study shows long-term maintenance of clinically relevant effects.”
 

Significant Improvement in OA Pain, Stiffness, Physical Function

In the OA randomized controlled trial, 64 people with hip and/or knee OA and metabolic syndrome were randomized to the PFJ intervention or usual care (waitlist control group). A total of 62 participants (including those in the control group previously) entered the long-term effectiveness study, and 44 had 2 years of follow-up data for analysis. Twenty participants dropped out, with most being unreachable or too busy.

“The PFJ program is a theoretical and practical program where people learn about and follow a whole food, plant-based diet, and receive advice on sleep and stress management and exercise,” said Dr. Wagenaar.

The program lasted 16 weeks with group sessions of 6-12 participants. The diet was a plant-based version of the Dutch dietary guidelines with a focus on unprocessed food. It was rich in whole grains, legumes, nuts, seeds, fruit, and vegetables, but without calorie restrictions and participants had one-to-one contact with a dietitian. The exercise advice followed the Dutch exercise guidelines, which advise 150 minutes of moderate to intense exercise per week, as well as twice-weekly muscle strength exercises, noted Dr. Wagenaar.

The 2-year follow-up study involved twice-yearly visits and six adherence-promoting webinars per year, as well as monthly newsletters. Researchers also monitored changes in medication intensity (classified as “increased,” “stable,” or “decreased/stopped”) between the start of the PFJ intervention and end of the 2-year extension study, and they were grouped into medications for pain, blood pressure, glucose, and cholesterol.

Participants were encouraged to try to avoid making changes to medication during the intervention phase, but they could do so during the 2-year extension study, said Dr. Wagenaar. In fact, the researchers actively monitored and quantified medication changes between the start of the PFJ intervention and end of the 2-year follow-up period.

Patients in the 16-week trial had an average age of 64 years, 84% were women, and their mean body mass index (BMI) was 33 kg/m². A total of 73% had knee OA and 78% hip OA, and their mean WOMAC score was 38.2, indicative of moderate to severe OA.

In participants who completed the 2-year extension study, the primary outcome (WOMAC score for mean stiffness and physical function) showed a significant improvement of −9.1 (95% CI, −12.8 to −5.3; P < .0001) compared with the start of the PFJ intervention.

“Looking at individual components of the WOMAC score — pain, stiffness, and physical function — we found these also all significantly improved at the end of the 2-year extension phase,” reported Dr. Wagenaar.

She added that after 2 years, there were significant improvements in weight loss (from 94.9 to 92.1 kg), BMI (from 33.3 to 32 kg/m²), and waist circumference (from 110 to 106.7 cm).

By the end of the trial and at 1 year of the extension study, there were significant improvements in A1c, fasting blood glucose, and low-density lipoprotein cholesterol, but at 2 years, these were no longer significant.

Regarding medications use, Dr. Wagenaar reported that, overall, there was no net change in use of pain, glucose-lowering, or hypertension medications, but 44% of patients using cholesterol-lowering medications were able to lower their dose or stop them.
 

Disease Activity Improvement and Medication Reduction in RA

Turning to the study of the intervention in patients with RA, 77 people (DAS28 ≥ 2.6 and ≤ 5.1, mild to moderate disease) were randomized to receive either the PFJ intervention in addition to usual care or only usual care (control group). Of these, 48 (62%) from both the intervention and control groups also completed the 2-year follow-up. The details of the PFJ intervention and the extension study for RA were the same as for the OA patient group.

Dr. Wagenaar commented on how they tried to individualize the exercise part of the program. “We noticed many of the RA patients asked too much of their body, while in contrast, those with OA were too hesitant,” she said. “We decided to focus on people’s own physical barriers, and we wanted to protect these. Sometimes, people needed to move more, and at other times, we had to tell people to slow down. Often, we advised people to move more by integrating exercise into their daily life.”

Similar to the OA study, patients were asked to try to avoid changing their medications in the 16-week study. “In the extension study, they were encouraged to reduce their medication in collaboration with their rheumatologist,” explained Wagenaar, who monitored any changes.

Differences were quantified according to medication groups comprising rheumatic medications, as well as pain, blood pressure, glucose-lowering, and cholesterol medications, and changes were categorized as increased, stable, or decreased/stopped.

Again, participants were mostly women (92%) with an average age of 55 years, BMI of 26 kg/m², and DAS28 of 3.85 at baseline. Dropout reasons were similar to those for OA, and over 85% of participants were on medications.

During the 16-week trial period, the DAS28 changed more in the intervention participants than in the controls, and after 2 years of follow-up, DAS28 was significantly lower than baseline with a mean difference of −0.9 (95% CI, −1.2 to −0.6; P < .0001).

“Comparing with the literature, the drop in DAS28 was similar to that seen with medication, so it’s a very significant reduction,” remarked Dr. Wagenaar.

Mean tender joint count dropped from 3 to 0, and general health components of the DAS28 improved significantly over the intervention and over the 2-year follow-up, whereas there was no significant difference in the already low erythrocyte sedimentation rate and swollen joint count compared with baseline. C-reactive protein (CRP) changed from 3.2 to 1.3 mg/L over the 2-year follow-up. High-density lipoprotein increased from 1.6 to 1.8 mmol/L.

A total of 44% of people using antirheumatic medication decreased or stopped them after the 2-year extension.

Dr. Wagenaar went on to say that focus group findings suggested that “participants were very enthusiastic about the program despite it largely involving lifestyle change, and this is reflected in our low dropout rates after the trial and 1-year extension [20% for OA and RA].” There were more dropouts in year 2 of the extension.

In an interview, Dr. Wagenaar explained why she felt the program had been so well received. “People in the program felt like they had more control over their disease, and they felt listened to.”
 

Mechanisms Underpinning PFJ

Dr. Wagenaar and colleagues also sought to determine the possible mechanisms underlying the clinical effects of the plant-based diet on RA. “With RA, we have the mucosal origins hypothesis, which suggests RA is triggered at the mucosal site [of the gut] in genetically predisposed individuals, and this consequently transfers to the synovial [fluid in] joints,” she said.

“On top of this, we know that fiber protects our gut barrier and therefore reduces inflammation. The PFJ intervention is a very high-fiber program, so our hypothesis is that it might help [strengthen] the barrier,” she explained.

Dr. Wagenaar and colleagues collected fecal samples from patients and measured the albumin and calprotectin in them, which are both indicators of the gut barrier function. The researchers analyzed metabolomic data and found that fecal albumin — considered a gut barrier integrity marker — decreased significantly in the intervention group. In patients with RA, this improvement corresponded with an improvement in DAS28, the researchers reported in a poster at the meeting.

“Patients who had the greatest improvement in their gut barrier function also showed the greatest improvement in the DAS28 score, suggestive of a possible link between gut barrier improvement and clinical effects.”

They did not identify any change in calprotectin, an inflammation marker, but Dr. Wagenaar said this might change later. “We found that in those on the intervention, at 4 months, the CRP wasn’t reduced, but 1 year later it was.”

The metabolite lenticin, a lentil intake biomarker considered protective against inflammation and osteoclastic differentiation, also increased. Tryptophan was also reduced in people on the PFJ intervention.

Fernando Estevez-Lopez, PhD, a sports scientist at Harvard T.H. Chan School of Public Health, Boston, who specializes in physical activity and behavioral change in rheumatology patients, co-moderated the session and remarked that, “In this study, they did a brilliant job with encouraging participants to follow the program. The design and methods were really good — the sample size was good, and they followed people up. Also, these researchers come from Reade [a medical research center in Amsterdam University Medical Center] where they are well known for applying their research findings to the clinic,” he said.

“In terms of physical activity, we really mean increasing the time spent moving, for example, gentle activity such as walking, or changing behaviors in people with OA and RA. We don’t want them to have more pain the next day.”

Dr. Wagenaar reported receiving a grant from ZonMw (The Netherlands Organization for Health Research and Development). She and colleagues hold shares in Plants for Health, a limited liability company. Dr. Estevez-Lopez reported having no relevant disclosures.
 

A version of this article appeared on Medscape.com.

UPDATED July 8, 2024 // Editor's note: This article has been revised to give a more nuanced view from Yael Klionsky, MD, about the need for more accurate and consistent gout management guidelines for busy primary care clinicians who often rely on them in clinical practice.

VIENNA — The first multicenter randomized trial in gout to compare treat-to-target (T2T) and treat for symptom avoidance (T2S) strategies has finally generated data to make the guideline-recommended practice of T2T evidence-based.

The T2T strategy may be guideline-endorsed, but it has never been validated, contended Anusha Moses, MSc, a researcher and PhD candidate at the University of Twente, Enschede, the Netherlands. She argued that this controlled trial fills an evidence gap.

T2T is defined as maintaining a serum uric acid (sUA) level below the physiologic threshold level of 36 mmol/L (< 6 mg/dL). T2S, in contrast, is a strategy of symptom control, typically basing therapy on suppression of symptoms independent of sUA, Dr. Moses explained. 

Ted Bosworth/Medscape Medical News

Both the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) have already endorsed T2T, but other organizations, such as the American College of Physicians (ACP), still accept symptom-based treatment in its gout clinical practice guideline, according to Dr. Moses.

The results of the trial were not surprising based on the pathophysiology of gout. Elevated sUA is considered the driver of both flares and the complications of gout. This well-established association led to endorsement of T2T in guidelines from organizations such as EULAR, but Dr. Moses said a controlled trial allows this to be declared as evidence based.

To provide proof that T2T is superior, 308 gout patients at eight centers were randomized to one of the two strategies in a trial called GO TEST OVERTURE. In the T2T arm, commonly used therapies, such as allopurinol, benzbromarone, and febuxostat were employed to achieve and maintain a target sUA of < 0.36 mmol/L. In the T2S comparator arm, the same drugs were offered to control symptoms and prevent recurrences, but sUA levels were not used to guide treatment. 

The 1-year results of a planned 2-year study were presented in an oral abstract session at the annual European Congress of Rheumatology. For this analysis, outcomes were compared in the last 6 months prior to the 1-year data analysis. When assessed at 2 years, the comparison will again be made in the prior 6 months of the study.

For the primary endpoint of flares defined by the validated Gallo criteria, the mean rates were 1.3 for T2T and 1.85 for T2S (P < .001), Dr. Moses reported.

The reduced risk for flares correlated with the greater proportion of patients with sUA < 0.36 mmol/L. These proportions were 72% and 26% (P < .001) for the T2T and T2S groups, respectively. The mean sUA levels were 0.31 mmol/L and 0.42 mmol/L (P < .001), respectively.

At the 1-year mark, none of the secondary endpoints reached statistical significance. These included mean numeric rating pain scale (2.46 vs 2.41), the proportion of patients in remission (8% vs 5.7%), and the mean Health Assessment Questionnaire-Disability Index score (0.65 vs 0.62), according to Dr. Moses, who said all of these endpoints will continue to be followed in the planned second year of the study.

At baseline, there were no differences in any of the variables evaluated, including age (about 62.5 years in both groups), proportion of patients with a body mass index > 30 kg/m2 (about 62%), sUA (about 0.5 mmol/L), or estimated glomerular filtration rate (about 70 mL/min/1.73 m2).
 

Nonspecialists Should Heed the Results

According to Yael Klionsky, MD, a clinical assistant professor of rheumatology and immunology at Wake Forest University School of Medicine, Winston-Salem, North Carolina, these data are not a surprise. 

Even before this trial was completed, the message for clinicians is that they “should be focused on maintaining serum uric acid levels below physiological levels to improve outcomes” in patients with recurrent flares, said Klionsky, citing the validated EULAR and ACR guidelines.

While the ACP does still consider T2S acceptable as a strategy for chronic gout management, Klionsky pointed out that those guidelines have not been updated recently. Specialists in the treatment of gout do not need any more evidence that the T2T approach leads to better outcomes.

However, she agreed with the principle that non-rheumatologists need to be reached with better guidance in regard to gout management. While she expects the ACP to endorse T2T the next time their guidelines are updated, she hopes that primary care physicians recognize that T2T should now be a standard.

“In a 10- to 20-minute visit, managing multiple chronic conditions can be a challenge in primary care,” Klionsky said. “Many clinicians rely on guidelines so it is important to have consistent and accurate information.”

There is currently some distance between specialists and primary care physicians regarding the goals of gout management, according to a study that Klionsky presented at EULAR 2024. In a survey, nonspecialists and specialists did not perceive treatment priorities in the same way.

In this survey, which elicited responses from 151 rheumatologists, 150 nephrologists, and 102 primary care physicians, there was general agreement that preventing flares is a priority, but only 30% of primary care physicians and 35% of nephrologists vs 64% of rheumatologists identified the T2T target of < 0.36 mmol/L as a key step in reaching this goal.

Conversely, 58% of primary care physicians and 42% of nephrologists vs only 34% of rheumatologists considered absence of gout pain to be in the top three criteria.

In addition to the fact that primary care physicians differ from specialists in their goals for gout treatment, these data “highlight the need for the importance of a standardized definition of gout remission that includes serum uric acid control,” Dr. Klionsky said. She further thinks that this type of guidance should be disseminated to nonspecialists.

Dr. Moses reported no potential conflicts of interest. Dr. Klionsky reported financial relationships with Amgen, AstraZeneca, Eli Lilly, and MedIQ.

A version of this article appeared on Medscape.com.

UPDATED July 8, 2024 // Editor's note: This article has been revised to give a more nuanced view from Yael Klionsky, MD, about the need for more accurate and consistent gout management guidelines for busy primary care clinicians who often rely on them in clinical practice.

VIENNA — The first multicenter randomized trial in gout to compare treat-to-target (T2T) and treat for symptom avoidance (T2S) strategies has finally generated data to make the guideline-recommended practice of T2T evidence-based.

The T2T strategy may be guideline-endorsed, but it has never been validated, contended Anusha Moses, MSc, a researcher and PhD candidate at the University of Twente, Enschede, the Netherlands. She argued that this controlled trial fills an evidence gap.

T2T is defined as maintaining a serum uric acid (sUA) level below the physiologic threshold level of 36 mmol/L (< 6 mg/dL). T2S, in contrast, is a strategy of symptom control, typically basing therapy on suppression of symptoms independent of sUA, Dr. Moses explained. 

Ted Bosworth/Medscape Medical News

Both the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) have already endorsed T2T, but other organizations, such as the American College of Physicians (ACP), still accept symptom-based treatment in its gout clinical practice guideline, according to Dr. Moses.

The results of the trial were not surprising based on the pathophysiology of gout. Elevated sUA is considered the driver of both flares and the complications of gout. This well-established association led to endorsement of T2T in guidelines from organizations such as EULAR, but Dr. Moses said a controlled trial allows this to be declared as evidence based.

To provide proof that T2T is superior, 308 gout patients at eight centers were randomized to one of the two strategies in a trial called GO TEST OVERTURE. In the T2T arm, commonly used therapies, such as allopurinol, benzbromarone, and febuxostat were employed to achieve and maintain a target sUA of < 0.36 mmol/L. In the T2S comparator arm, the same drugs were offered to control symptoms and prevent recurrences, but sUA levels were not used to guide treatment. 

The 1-year results of a planned 2-year study were presented in an oral abstract session at the annual European Congress of Rheumatology. For this analysis, outcomes were compared in the last 6 months prior to the 1-year data analysis. When assessed at 2 years, the comparison will again be made in the prior 6 months of the study.

For the primary endpoint of flares defined by the validated Gallo criteria, the mean rates were 1.3 for T2T and 1.85 for T2S (P < .001), Dr. Moses reported.

The reduced risk for flares correlated with the greater proportion of patients with sUA < 0.36 mmol/L. These proportions were 72% and 26% (P < .001) for the T2T and T2S groups, respectively. The mean sUA levels were 0.31 mmol/L and 0.42 mmol/L (P < .001), respectively.

At the 1-year mark, none of the secondary endpoints reached statistical significance. These included mean numeric rating pain scale (2.46 vs 2.41), the proportion of patients in remission (8% vs 5.7%), and the mean Health Assessment Questionnaire-Disability Index score (0.65 vs 0.62), according to Dr. Moses, who said all of these endpoints will continue to be followed in the planned second year of the study.

At baseline, there were no differences in any of the variables evaluated, including age (about 62.5 years in both groups), proportion of patients with a body mass index > 30 kg/m2 (about 62%), sUA (about 0.5 mmol/L), or estimated glomerular filtration rate (about 70 mL/min/1.73 m2).
 

Nonspecialists Should Heed the Results

According to Yael Klionsky, MD, a clinical assistant professor of rheumatology and immunology at Wake Forest University School of Medicine, Winston-Salem, North Carolina, these data are not a surprise. 

Even before this trial was completed, the message for clinicians is that they “should be focused on maintaining serum uric acid levels below physiological levels to improve outcomes” in patients with recurrent flares, said Klionsky, citing the validated EULAR and ACR guidelines.

While the ACP does still consider T2S acceptable as a strategy for chronic gout management, Klionsky pointed out that those guidelines have not been updated recently. Specialists in the treatment of gout do not need any more evidence that the T2T approach leads to better outcomes.

However, she agreed with the principle that non-rheumatologists need to be reached with better guidance in regard to gout management. While she expects the ACP to endorse T2T the next time their guidelines are updated, she hopes that primary care physicians recognize that T2T should now be a standard.

“In a 10- to 20-minute visit, managing multiple chronic conditions can be a challenge in primary care,” Klionsky said. “Many clinicians rely on guidelines so it is important to have consistent and accurate information.”

There is currently some distance between specialists and primary care physicians regarding the goals of gout management, according to a study that Klionsky presented at EULAR 2024. In a survey, nonspecialists and specialists did not perceive treatment priorities in the same way.

In this survey, which elicited responses from 151 rheumatologists, 150 nephrologists, and 102 primary care physicians, there was general agreement that preventing flares is a priority, but only 30% of primary care physicians and 35% of nephrologists vs 64% of rheumatologists identified the T2T target of < 0.36 mmol/L as a key step in reaching this goal.

Conversely, 58% of primary care physicians and 42% of nephrologists vs only 34% of rheumatologists considered absence of gout pain to be in the top three criteria.

In addition to the fact that primary care physicians differ from specialists in their goals for gout treatment, these data “highlight the need for the importance of a standardized definition of gout remission that includes serum uric acid control,” Dr. Klionsky said. She further thinks that this type of guidance should be disseminated to nonspecialists.

Dr. Moses reported no potential conflicts of interest. Dr. Klionsky reported financial relationships with Amgen, AstraZeneca, Eli Lilly, and MedIQ.

A version of this article appeared on Medscape.com.

UPDATED July 8, 2024 // Editor's note: This article has been revised to give a more nuanced view from Yael Klionsky, MD, about the need for more accurate and consistent gout management guidelines for busy primary care clinicians who often rely on them in clinical practice.

VIENNA — The first multicenter randomized trial in gout to compare treat-to-target (T2T) and treat for symptom avoidance (T2S) strategies has finally generated data to make the guideline-recommended practice of T2T evidence-based.

The T2T strategy may be guideline-endorsed, but it has never been validated, contended Anusha Moses, MSc, a researcher and PhD candidate at the University of Twente, Enschede, the Netherlands. She argued that this controlled trial fills an evidence gap.

T2T is defined as maintaining a serum uric acid (sUA) level below the physiologic threshold level of 36 mmol/L (< 6 mg/dL). T2S, in contrast, is a strategy of symptom control, typically basing therapy on suppression of symptoms independent of sUA, Dr. Moses explained. 

Ted Bosworth/Medscape Medical News

Both the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) have already endorsed T2T, but other organizations, such as the American College of Physicians (ACP), still accept symptom-based treatment in its gout clinical practice guideline, according to Dr. Moses.

The results of the trial were not surprising based on the pathophysiology of gout. Elevated sUA is considered the driver of both flares and the complications of gout. This well-established association led to endorsement of T2T in guidelines from organizations such as EULAR, but Dr. Moses said a controlled trial allows this to be declared as evidence based.

To provide proof that T2T is superior, 308 gout patients at eight centers were randomized to one of the two strategies in a trial called GO TEST OVERTURE. In the T2T arm, commonly used therapies, such as allopurinol, benzbromarone, and febuxostat were employed to achieve and maintain a target sUA of < 0.36 mmol/L. In the T2S comparator arm, the same drugs were offered to control symptoms and prevent recurrences, but sUA levels were not used to guide treatment. 

The 1-year results of a planned 2-year study were presented in an oral abstract session at the annual European Congress of Rheumatology. For this analysis, outcomes were compared in the last 6 months prior to the 1-year data analysis. When assessed at 2 years, the comparison will again be made in the prior 6 months of the study.

For the primary endpoint of flares defined by the validated Gallo criteria, the mean rates were 1.3 for T2T and 1.85 for T2S (P < .001), Dr. Moses reported.

The reduced risk for flares correlated with the greater proportion of patients with sUA < 0.36 mmol/L. These proportions were 72% and 26% (P < .001) for the T2T and T2S groups, respectively. The mean sUA levels were 0.31 mmol/L and 0.42 mmol/L (P < .001), respectively.

At the 1-year mark, none of the secondary endpoints reached statistical significance. These included mean numeric rating pain scale (2.46 vs 2.41), the proportion of patients in remission (8% vs 5.7%), and the mean Health Assessment Questionnaire-Disability Index score (0.65 vs 0.62), according to Dr. Moses, who said all of these endpoints will continue to be followed in the planned second year of the study.

At baseline, there were no differences in any of the variables evaluated, including age (about 62.5 years in both groups), proportion of patients with a body mass index > 30 kg/m2 (about 62%), sUA (about 0.5 mmol/L), or estimated glomerular filtration rate (about 70 mL/min/1.73 m2).
 

Nonspecialists Should Heed the Results

According to Yael Klionsky, MD, a clinical assistant professor of rheumatology and immunology at Wake Forest University School of Medicine, Winston-Salem, North Carolina, these data are not a surprise. 

Even before this trial was completed, the message for clinicians is that they “should be focused on maintaining serum uric acid levels below physiological levels to improve outcomes” in patients with recurrent flares, said Klionsky, citing the validated EULAR and ACR guidelines.

While the ACP does still consider T2S acceptable as a strategy for chronic gout management, Klionsky pointed out that those guidelines have not been updated recently. Specialists in the treatment of gout do not need any more evidence that the T2T approach leads to better outcomes.

However, she agreed with the principle that non-rheumatologists need to be reached with better guidance in regard to gout management. While she expects the ACP to endorse T2T the next time their guidelines are updated, she hopes that primary care physicians recognize that T2T should now be a standard.

“In a 10- to 20-minute visit, managing multiple chronic conditions can be a challenge in primary care,” Klionsky said. “Many clinicians rely on guidelines so it is important to have consistent and accurate information.”

There is currently some distance between specialists and primary care physicians regarding the goals of gout management, according to a study that Klionsky presented at EULAR 2024. In a survey, nonspecialists and specialists did not perceive treatment priorities in the same way.

In this survey, which elicited responses from 151 rheumatologists, 150 nephrologists, and 102 primary care physicians, there was general agreement that preventing flares is a priority, but only 30% of primary care physicians and 35% of nephrologists vs 64% of rheumatologists identified the T2T target of < 0.36 mmol/L as a key step in reaching this goal.

Conversely, 58% of primary care physicians and 42% of nephrologists vs only 34% of rheumatologists considered absence of gout pain to be in the top three criteria.

In addition to the fact that primary care physicians differ from specialists in their goals for gout treatment, these data “highlight the need for the importance of a standardized definition of gout remission that includes serum uric acid control,” Dr. Klionsky said. She further thinks that this type of guidance should be disseminated to nonspecialists.

Dr. Moses reported no potential conflicts of interest. Dr. Klionsky reported financial relationships with Amgen, AstraZeneca, Eli Lilly, and MedIQ.

A version of this article appeared on Medscape.com.

VIENNA — Pneumococcal vaccination administered 1 month prior to starting methotrexate (MTX) in patients with rheumatoid arthritis (RA) allows a significantly higher immunological response at 1 month and does not affect disease control at 1 year, compared with starting MTX simultaneously with the vaccination, according to data from a randomized trial presented at the annual European Congress of Rheumatology.

“Our patients are more susceptible to infection due to immunosuppressive therapy, and it’s recommended they receive vaccination against pneumococcal infection,” the lead author Jacques Morel, MD, PhD, said in his presentation of results from the VACIMRA study.

Timing the vaccination against pneumococcal disease when initiating MTX in clinical practice has been a point of uncertainty, noted Dr. Morel, a rheumatologist from Centre Hospitalier Universitaire, Montpellier, France.

“How can we deal with this in clinical practice where one recommendation is to vaccine before initiation of methotrexate, but it is also recommended to start methotrexate as soon as the diagnosis of RA is made?” he asked.
 

Comparing Humoral Response of MTX Started Immediately or 1 Month Post-Vaccination

The prospective, randomized, multicenter trial aimed to compare the rate of humoral immunological response against pneumococcal 13-valent conjugate vaccine (PCV13) in patients with RA who had a Disease Activity Score in 28 joints (DAS28) > 3.2, never taken MTX, and never been vaccinated against pneumococcus. Patients were vaccinated either 1 month before MTX initiation (n = 126) or simultaneously with MTX (n = 123). Oral glucocorticoids were allowed but only at < 10 mg/d. Following PCV13 vaccination, all patients also received the 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later.

Concentrations of immunoglobulin (Ig) G antibodies against the 13 serotypes contained within PCV13 were measured using enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic killing assay (OPA) at baseline and during follow-up at 1, 3, 6, and 12 months.

Positive antibody response was defined as a twofold or more increase in the IgG concentration using ELISA. The main outcome was the responder rates at 1 month after PCV13, defined by at least three positive antibody responses out of five of the target PVC13 serotypes (1, 3, 5, 7F, and 19A) using ELISA or OPA. Secondary outcomes included comparisons of the percentage of patients responding to each of the 13 vaccine serotypes at 1 month and after the boost with PPV23 and at 3, 6, and 12 months after vaccination with PCV13. The researchers also measured disease activity, infections, and side effects throughout the study.

Dr. Morel highlighted that all the patients had very early RA of less than 6 months, and that their characteristics at baseline were similar in both groups with 70% women, mean age 55.6 years, RA duration 2 months, 69% positive for anticitrullinated protein antibodies, 21% with erosive disease, and a DAS28 based on C-reactive protein of 4.6.

Response rates in those receiving MTX 1 month after vaccination were significantly higher at 88% with ELISA than those at 75% for immediate vaccination (P < .01) and 96% vs 88% with OPA (P = .02). These responder proportions persisted at the 12-month follow-up measurements, remaining higher in the delayed MTX group for both assays and across the 13 serotypes.

Showing a graph of the antibody responses, Dr. Morel explained that “at 12 months, the curves start to converge, but the difference in antibody titers were still significant for eight of the 13 serotypes.”
 

Disease Activity Not Adversely Affected by Starting MTX 1 Month Later

Regarding medication doses at 12 months, the cumulative glucocorticoid doses were similar between groups during the follow-up. As expected, the 1-year cumulative dose of MTX was higher in those given the drug immediately after vaccination vs delayed (826 vs 734 mg), but the weekly mean doses of MTX were similar at 3, 6, and 12 months between the two groups, and likewise, the use of targeted disease-modifying antirheumatic drugs (DMARDs) at 1 year was comparable. The cumulative glucocorticoid dose at 12 months was similar at 1716 mg with delayed MTX and 1613 mg with immediate MTX.

Not unexpectedly, at 1 month, DAS28 scores were higher with delayed vs immediate MTX at 3.95 vs 3.38 for DAS28-ESR and 3.54 vs 3.01 for DAS28-CRP (P < .01), but after the first month, DAS28 scores were similar between the two groups.

No significant differences were found between the groups for adverse event rates within 7 days of receiving PCV13, with local and systemic reactions occurring at 60%-61% and 50%-58%, respectively; fever at 0%-4%; and severe infections at 12%.

Finally, no difference was found in terms of serious adverse events between groups, with one pneumococcal infection with delayed MTX during follow-up, and there were no unexpected side effects observed with the PCV13 and PPV23 vaccinations.
 

Rheumatologists’ Reactions

Ernest Choy, MD, head of rheumatology and translational research at the Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, asked if any individual showed no humoral response at all rather than a reduced response. “I ask because if there is no humoral response, then they are at very high risk, and there will be clinical relevance to that.”

Dr. Morel replied that “one serotype showed no response, at least according to the assays used, but we don’t know why. We analyzed at the population [level], not at the individual level, so it is difficult to answer the question.”

Another delegate asked what the participants thought about delaying MTX by 1 month. “When we tell the patient we need to vaccinate before we can use methotrexate [because] otherwise, we will reduce the response to the vaccination, then patient accepts it,” said Dr. Morel, adding that, “we allowed a minimal dose of steroids, and we saw from the results that the DAS28 at 1 month had changed.”

Co-moderator Katerina Chatzidionysiou, MD, PhD, a consultant rheumatologist and head of the Clinical Trial Department Rheumatology Unit, Karolinska University Hospital, Stockholm, Sweden, said that “As a physician, I’d feel uncomfortable delaying MTX if they had very active disease even for a short period of time.”

Dr. Morel replied that, “Today, we have so many drugs that can control the disease, for example, the targeted DMARDs. Progression does not show much variation, and we know x-ray progression with today’s drugs is a lot less than previously.”

Dr. Morel reported financial relationships with AbbVie, Amgen, Biogen, Bristol Myers Squibb, Fresenius Kabi, Galapagos, GlaxoSmithKline, Lilly, Medac, Nordic Pharma, Novartis, Pfizer, Sandoz, Sanofi, Boehringer Ingelheim, and Servier. Dr. Choy had no relevant financial relationships of relevance to this study.

A version of this article appeared on Medscape.com.

VIENNA — Pneumococcal vaccination administered 1 month prior to starting methotrexate (MTX) in patients with rheumatoid arthritis (RA) allows a significantly higher immunological response at 1 month and does not affect disease control at 1 year, compared with starting MTX simultaneously with the vaccination, according to data from a randomized trial presented at the annual European Congress of Rheumatology.

“Our patients are more susceptible to infection due to immunosuppressive therapy, and it’s recommended they receive vaccination against pneumococcal infection,” the lead author Jacques Morel, MD, PhD, said in his presentation of results from the VACIMRA study.

Timing the vaccination against pneumococcal disease when initiating MTX in clinical practice has been a point of uncertainty, noted Dr. Morel, a rheumatologist from Centre Hospitalier Universitaire, Montpellier, France.

“How can we deal with this in clinical practice where one recommendation is to vaccine before initiation of methotrexate, but it is also recommended to start methotrexate as soon as the diagnosis of RA is made?” he asked.
 

Comparing Humoral Response of MTX Started Immediately or 1 Month Post-Vaccination

The prospective, randomized, multicenter trial aimed to compare the rate of humoral immunological response against pneumococcal 13-valent conjugate vaccine (PCV13) in patients with RA who had a Disease Activity Score in 28 joints (DAS28) > 3.2, never taken MTX, and never been vaccinated against pneumococcus. Patients were vaccinated either 1 month before MTX initiation (n = 126) or simultaneously with MTX (n = 123). Oral glucocorticoids were allowed but only at < 10 mg/d. Following PCV13 vaccination, all patients also received the 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later.

Concentrations of immunoglobulin (Ig) G antibodies against the 13 serotypes contained within PCV13 were measured using enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic killing assay (OPA) at baseline and during follow-up at 1, 3, 6, and 12 months.

Positive antibody response was defined as a twofold or more increase in the IgG concentration using ELISA. The main outcome was the responder rates at 1 month after PCV13, defined by at least three positive antibody responses out of five of the target PVC13 serotypes (1, 3, 5, 7F, and 19A) using ELISA or OPA. Secondary outcomes included comparisons of the percentage of patients responding to each of the 13 vaccine serotypes at 1 month and after the boost with PPV23 and at 3, 6, and 12 months after vaccination with PCV13. The researchers also measured disease activity, infections, and side effects throughout the study.

Dr. Morel highlighted that all the patients had very early RA of less than 6 months, and that their characteristics at baseline were similar in both groups with 70% women, mean age 55.6 years, RA duration 2 months, 69% positive for anticitrullinated protein antibodies, 21% with erosive disease, and a DAS28 based on C-reactive protein of 4.6.

Response rates in those receiving MTX 1 month after vaccination were significantly higher at 88% with ELISA than those at 75% for immediate vaccination (P < .01) and 96% vs 88% with OPA (P = .02). These responder proportions persisted at the 12-month follow-up measurements, remaining higher in the delayed MTX group for both assays and across the 13 serotypes.

Showing a graph of the antibody responses, Dr. Morel explained that “at 12 months, the curves start to converge, but the difference in antibody titers were still significant for eight of the 13 serotypes.”
 

Disease Activity Not Adversely Affected by Starting MTX 1 Month Later

Regarding medication doses at 12 months, the cumulative glucocorticoid doses were similar between groups during the follow-up. As expected, the 1-year cumulative dose of MTX was higher in those given the drug immediately after vaccination vs delayed (826 vs 734 mg), but the weekly mean doses of MTX were similar at 3, 6, and 12 months between the two groups, and likewise, the use of targeted disease-modifying antirheumatic drugs (DMARDs) at 1 year was comparable. The cumulative glucocorticoid dose at 12 months was similar at 1716 mg with delayed MTX and 1613 mg with immediate MTX.

Not unexpectedly, at 1 month, DAS28 scores were higher with delayed vs immediate MTX at 3.95 vs 3.38 for DAS28-ESR and 3.54 vs 3.01 for DAS28-CRP (P < .01), but after the first month, DAS28 scores were similar between the two groups.

No significant differences were found between the groups for adverse event rates within 7 days of receiving PCV13, with local and systemic reactions occurring at 60%-61% and 50%-58%, respectively; fever at 0%-4%; and severe infections at 12%.

Finally, no difference was found in terms of serious adverse events between groups, with one pneumococcal infection with delayed MTX during follow-up, and there were no unexpected side effects observed with the PCV13 and PPV23 vaccinations.
 

Rheumatologists’ Reactions

Ernest Choy, MD, head of rheumatology and translational research at the Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, asked if any individual showed no humoral response at all rather than a reduced response. “I ask because if there is no humoral response, then they are at very high risk, and there will be clinical relevance to that.”

Dr. Morel replied that “one serotype showed no response, at least according to the assays used, but we don’t know why. We analyzed at the population [level], not at the individual level, so it is difficult to answer the question.”

Another delegate asked what the participants thought about delaying MTX by 1 month. “When we tell the patient we need to vaccinate before we can use methotrexate [because] otherwise, we will reduce the response to the vaccination, then patient accepts it,” said Dr. Morel, adding that, “we allowed a minimal dose of steroids, and we saw from the results that the DAS28 at 1 month had changed.”

Co-moderator Katerina Chatzidionysiou, MD, PhD, a consultant rheumatologist and head of the Clinical Trial Department Rheumatology Unit, Karolinska University Hospital, Stockholm, Sweden, said that “As a physician, I’d feel uncomfortable delaying MTX if they had very active disease even for a short period of time.”

Dr. Morel replied that, “Today, we have so many drugs that can control the disease, for example, the targeted DMARDs. Progression does not show much variation, and we know x-ray progression with today’s drugs is a lot less than previously.”

Dr. Morel reported financial relationships with AbbVie, Amgen, Biogen, Bristol Myers Squibb, Fresenius Kabi, Galapagos, GlaxoSmithKline, Lilly, Medac, Nordic Pharma, Novartis, Pfizer, Sandoz, Sanofi, Boehringer Ingelheim, and Servier. Dr. Choy had no relevant financial relationships of relevance to this study.

A version of this article appeared on Medscape.com.

VIENNA — Pneumococcal vaccination administered 1 month prior to starting methotrexate (MTX) in patients with rheumatoid arthritis (RA) allows a significantly higher immunological response at 1 month and does not affect disease control at 1 year, compared with starting MTX simultaneously with the vaccination, according to data from a randomized trial presented at the annual European Congress of Rheumatology.

“Our patients are more susceptible to infection due to immunosuppressive therapy, and it’s recommended they receive vaccination against pneumococcal infection,” the lead author Jacques Morel, MD, PhD, said in his presentation of results from the VACIMRA study.

Timing the vaccination against pneumococcal disease when initiating MTX in clinical practice has been a point of uncertainty, noted Dr. Morel, a rheumatologist from Centre Hospitalier Universitaire, Montpellier, France.

“How can we deal with this in clinical practice where one recommendation is to vaccine before initiation of methotrexate, but it is also recommended to start methotrexate as soon as the diagnosis of RA is made?” he asked.
 

Comparing Humoral Response of MTX Started Immediately or 1 Month Post-Vaccination

The prospective, randomized, multicenter trial aimed to compare the rate of humoral immunological response against pneumococcal 13-valent conjugate vaccine (PCV13) in patients with RA who had a Disease Activity Score in 28 joints (DAS28) > 3.2, never taken MTX, and never been vaccinated against pneumococcus. Patients were vaccinated either 1 month before MTX initiation (n = 126) or simultaneously with MTX (n = 123). Oral glucocorticoids were allowed but only at < 10 mg/d. Following PCV13 vaccination, all patients also received the 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later.

Concentrations of immunoglobulin (Ig) G antibodies against the 13 serotypes contained within PCV13 were measured using enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic killing assay (OPA) at baseline and during follow-up at 1, 3, 6, and 12 months.

Positive antibody response was defined as a twofold or more increase in the IgG concentration using ELISA. The main outcome was the responder rates at 1 month after PCV13, defined by at least three positive antibody responses out of five of the target PVC13 serotypes (1, 3, 5, 7F, and 19A) using ELISA or OPA. Secondary outcomes included comparisons of the percentage of patients responding to each of the 13 vaccine serotypes at 1 month and after the boost with PPV23 and at 3, 6, and 12 months after vaccination with PCV13. The researchers also measured disease activity, infections, and side effects throughout the study.

Dr. Morel highlighted that all the patients had very early RA of less than 6 months, and that their characteristics at baseline were similar in both groups with 70% women, mean age 55.6 years, RA duration 2 months, 69% positive for anticitrullinated protein antibodies, 21% with erosive disease, and a DAS28 based on C-reactive protein of 4.6.

Response rates in those receiving MTX 1 month after vaccination were significantly higher at 88% with ELISA than those at 75% for immediate vaccination (P < .01) and 96% vs 88% with OPA (P = .02). These responder proportions persisted at the 12-month follow-up measurements, remaining higher in the delayed MTX group for both assays and across the 13 serotypes.

Showing a graph of the antibody responses, Dr. Morel explained that “at 12 months, the curves start to converge, but the difference in antibody titers were still significant for eight of the 13 serotypes.”
 

Disease Activity Not Adversely Affected by Starting MTX 1 Month Later

Regarding medication doses at 12 months, the cumulative glucocorticoid doses were similar between groups during the follow-up. As expected, the 1-year cumulative dose of MTX was higher in those given the drug immediately after vaccination vs delayed (826 vs 734 mg), but the weekly mean doses of MTX were similar at 3, 6, and 12 months between the two groups, and likewise, the use of targeted disease-modifying antirheumatic drugs (DMARDs) at 1 year was comparable. The cumulative glucocorticoid dose at 12 months was similar at 1716 mg with delayed MTX and 1613 mg with immediate MTX.

Not unexpectedly, at 1 month, DAS28 scores were higher with delayed vs immediate MTX at 3.95 vs 3.38 for DAS28-ESR and 3.54 vs 3.01 for DAS28-CRP (P < .01), but after the first month, DAS28 scores were similar between the two groups.

No significant differences were found between the groups for adverse event rates within 7 days of receiving PCV13, with local and systemic reactions occurring at 60%-61% and 50%-58%, respectively; fever at 0%-4%; and severe infections at 12%.

Finally, no difference was found in terms of serious adverse events between groups, with one pneumococcal infection with delayed MTX during follow-up, and there were no unexpected side effects observed with the PCV13 and PPV23 vaccinations.
 

Rheumatologists’ Reactions

Ernest Choy, MD, head of rheumatology and translational research at the Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, asked if any individual showed no humoral response at all rather than a reduced response. “I ask because if there is no humoral response, then they are at very high risk, and there will be clinical relevance to that.”

Dr. Morel replied that “one serotype showed no response, at least according to the assays used, but we don’t know why. We analyzed at the population [level], not at the individual level, so it is difficult to answer the question.”

Another delegate asked what the participants thought about delaying MTX by 1 month. “When we tell the patient we need to vaccinate before we can use methotrexate [because] otherwise, we will reduce the response to the vaccination, then patient accepts it,” said Dr. Morel, adding that, “we allowed a minimal dose of steroids, and we saw from the results that the DAS28 at 1 month had changed.”

Co-moderator Katerina Chatzidionysiou, MD, PhD, a consultant rheumatologist and head of the Clinical Trial Department Rheumatology Unit, Karolinska University Hospital, Stockholm, Sweden, said that “As a physician, I’d feel uncomfortable delaying MTX if they had very active disease even for a short period of time.”

Dr. Morel replied that, “Today, we have so many drugs that can control the disease, for example, the targeted DMARDs. Progression does not show much variation, and we know x-ray progression with today’s drugs is a lot less than previously.”

Dr. Morel reported financial relationships with AbbVie, Amgen, Biogen, Bristol Myers Squibb, Fresenius Kabi, Galapagos, GlaxoSmithKline, Lilly, Medac, Nordic Pharma, Novartis, Pfizer, Sandoz, Sanofi, Boehringer Ingelheim, and Servier. Dr. Choy had no relevant financial relationships of relevance to this study.

A version of this article appeared on Medscape.com.

It’s time to renew two of my three narcotic prescribing licenses. For the first time in my career, I’ve waffled on whether the financial outlay to the US Drug Enforcement Agency (DEA) is worth it. 

At $888 each, I’ve considered letting two licenses lapse because I only work part-time in Montana. But several friends advised me to keep a “spare” in case I transfer to a new location. 

I thought about just paying the fees until I could do a little more research, but there is no mechanism for a refund unless I die within the first year of the 3-year cycle, provide incorrect credit card digits, or accidentally duplicate payments.

The renewal fee is just part of the issue.
 

Mandatory 8-Hour Training

I also received an alert about the requirement for more “narcotics prescribing education” thanks to the Medication Access and Training Expansion Act (MATE). 

The requirement seems counterintuitive because opioid prescribing has decreased for the 10th consecutive year, according to the AMA Overdose Epidemic Report. The continuing rise in overdose deaths is largely due to illegitimate manufacturing of synthetic opioids. 

I’ve written zero outpatient narcotics prescriptions in the past 6 years, and I’ve written very few in my 33 years of practice. My use is limited to intravenous morphine for flash pulmonary edema or refractory angina, but unless you graduated from a training program within 5 years of the June 2023 mandate or are boarded in addiction medicine, there is no way to escape the 8-hour education requirement.

The problem is that these courses are never just 8 hours in duration. After signing up for one such CME course that cost $150, I was still dying of boredom and at risk for DVT 4 days later. That’s how long it took to sit through.

Instead of the 30 seconds it should have taken to review the simple instructions to deliver Narcan, there were scores of screens followed by juvenile quizlets and cartoons. All but about 2 hours out of the 4 days is now relegated to that category of “hours of my life that I can never get back.” Additionally, none of that mandatory “education” will change my prescribing habits one whit. 

And beware the penalty. 

Changes Needed

The only good thing that came of those 4 long days of opioid education was a motivation to drive change in our current licensing and educational experience. Why not use this opportunity to reform the DEA-physician/prescriber relationship? 

The educational requirements should be curtailed for those of us who do not provide outpatient narcotic prescriptions even if we use inpatient opioids. Meds with low abuse potential should be rescheduled to minimize who gets caught in the broad net of the education requirement. 

We should reduce overregulation of the legitimate prescribers by lowering, instead of increasing, licensing fees. We should change to a single license number that covers every state. In this digital age, there is no legitimate excuse to prevent this from happening. 

After all, the settlements from opioid manufacturers and distributors will in time total $50 billion. It seems that at least some of the responsibilities of the DEA could shift to states, cities, and towns. 

My friend Siamak Karimian, MD, who provides locum services in multiple states, pays for seven active DEA licenses every 3 years. He pointed out the hypocrisy in the current regulatory system: “It’s funny that you can have only one DEA or state license and work for the government in all other states or territories with no limits, including the VA, Indian healthcare systems, or prison systems.”

All other prescribers require a separate DEA number for every state. Ultimately, you’d think tracking prescriptions for a single DEA number should be far simpler than tracking someone with seven. 

Competent physicians not guilty of criminal overprescribing seem to be the last to be considered in nearly every healthcare endeavor these days. It would be refreshing if they would reduce our fees and prevent this waste of our time. 

And while we are at it, perhaps a more fitting punishment is due for Richard Sackler and all the Purdue Pharma–affiliated family members. The Sacklers will pay out $6 billion in exchange for immunity against civil litigation. That doesn’t seem like much when they are worth $11 billion. 

Perhaps they should be made to take an 8-hour course on opioid prescribing, annually and in perpetuity. Let’s see them complete a few quizlets and sit through screens of instruction on how to administer Naloxone. Of course, that would be a mild punishment for those who manufactured a drug that killed hundreds of thousands. But it would be a start. 
 

Dr. Walton-Shirley, a clinical cardiologist in Nashville, Tennessee, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

It’s time to renew two of my three narcotic prescribing licenses. For the first time in my career, I’ve waffled on whether the financial outlay to the US Drug Enforcement Agency (DEA) is worth it. 

At $888 each, I’ve considered letting two licenses lapse because I only work part-time in Montana. But several friends advised me to keep a “spare” in case I transfer to a new location. 

I thought about just paying the fees until I could do a little more research, but there is no mechanism for a refund unless I die within the first year of the 3-year cycle, provide incorrect credit card digits, or accidentally duplicate payments.

The renewal fee is just part of the issue.
 

Mandatory 8-Hour Training

I also received an alert about the requirement for more “narcotics prescribing education” thanks to the Medication Access and Training Expansion Act (MATE). 

The requirement seems counterintuitive because opioid prescribing has decreased for the 10th consecutive year, according to the AMA Overdose Epidemic Report. The continuing rise in overdose deaths is largely due to illegitimate manufacturing of synthetic opioids. 

I’ve written zero outpatient narcotics prescriptions in the past 6 years, and I’ve written very few in my 33 years of practice. My use is limited to intravenous morphine for flash pulmonary edema or refractory angina, but unless you graduated from a training program within 5 years of the June 2023 mandate or are boarded in addiction medicine, there is no way to escape the 8-hour education requirement.

The problem is that these courses are never just 8 hours in duration. After signing up for one such CME course that cost $150, I was still dying of boredom and at risk for DVT 4 days later. That’s how long it took to sit through.

Instead of the 30 seconds it should have taken to review the simple instructions to deliver Narcan, there were scores of screens followed by juvenile quizlets and cartoons. All but about 2 hours out of the 4 days is now relegated to that category of “hours of my life that I can never get back.” Additionally, none of that mandatory “education” will change my prescribing habits one whit. 

And beware the penalty. 

Changes Needed

The only good thing that came of those 4 long days of opioid education was a motivation to drive change in our current licensing and educational experience. Why not use this opportunity to reform the DEA-physician/prescriber relationship? 

The educational requirements should be curtailed for those of us who do not provide outpatient narcotic prescriptions even if we use inpatient opioids. Meds with low abuse potential should be rescheduled to minimize who gets caught in the broad net of the education requirement. 

We should reduce overregulation of the legitimate prescribers by lowering, instead of increasing, licensing fees. We should change to a single license number that covers every state. In this digital age, there is no legitimate excuse to prevent this from happening. 

After all, the settlements from opioid manufacturers and distributors will in time total $50 billion. It seems that at least some of the responsibilities of the DEA could shift to states, cities, and towns. 

My friend Siamak Karimian, MD, who provides locum services in multiple states, pays for seven active DEA licenses every 3 years. He pointed out the hypocrisy in the current regulatory system: “It’s funny that you can have only one DEA or state license and work for the government in all other states or territories with no limits, including the VA, Indian healthcare systems, or prison systems.”

All other prescribers require a separate DEA number for every state. Ultimately, you’d think tracking prescriptions for a single DEA number should be far simpler than tracking someone with seven. 

Competent physicians not guilty of criminal overprescribing seem to be the last to be considered in nearly every healthcare endeavor these days. It would be refreshing if they would reduce our fees and prevent this waste of our time. 

And while we are at it, perhaps a more fitting punishment is due for Richard Sackler and all the Purdue Pharma–affiliated family members. The Sacklers will pay out $6 billion in exchange for immunity against civil litigation. That doesn’t seem like much when they are worth $11 billion. 

Perhaps they should be made to take an 8-hour course on opioid prescribing, annually and in perpetuity. Let’s see them complete a few quizlets and sit through screens of instruction on how to administer Naloxone. Of course, that would be a mild punishment for those who manufactured a drug that killed hundreds of thousands. But it would be a start. 
 

Dr. Walton-Shirley, a clinical cardiologist in Nashville, Tennessee, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

It’s time to renew two of my three narcotic prescribing licenses. For the first time in my career, I’ve waffled on whether the financial outlay to the US Drug Enforcement Agency (DEA) is worth it. 

At $888 each, I’ve considered letting two licenses lapse because I only work part-time in Montana. But several friends advised me to keep a “spare” in case I transfer to a new location. 

I thought about just paying the fees until I could do a little more research, but there is no mechanism for a refund unless I die within the first year of the 3-year cycle, provide incorrect credit card digits, or accidentally duplicate payments.

The renewal fee is just part of the issue.
 

Mandatory 8-Hour Training

I also received an alert about the requirement for more “narcotics prescribing education” thanks to the Medication Access and Training Expansion Act (MATE). 

The requirement seems counterintuitive because opioid prescribing has decreased for the 10th consecutive year, according to the AMA Overdose Epidemic Report. The continuing rise in overdose deaths is largely due to illegitimate manufacturing of synthetic opioids. 

I’ve written zero outpatient narcotics prescriptions in the past 6 years, and I’ve written very few in my 33 years of practice. My use is limited to intravenous morphine for flash pulmonary edema or refractory angina, but unless you graduated from a training program within 5 years of the June 2023 mandate or are boarded in addiction medicine, there is no way to escape the 8-hour education requirement.

The problem is that these courses are never just 8 hours in duration. After signing up for one such CME course that cost $150, I was still dying of boredom and at risk for DVT 4 days later. That’s how long it took to sit through.

Instead of the 30 seconds it should have taken to review the simple instructions to deliver Narcan, there were scores of screens followed by juvenile quizlets and cartoons. All but about 2 hours out of the 4 days is now relegated to that category of “hours of my life that I can never get back.” Additionally, none of that mandatory “education” will change my prescribing habits one whit. 

And beware the penalty. 

Changes Needed

The only good thing that came of those 4 long days of opioid education was a motivation to drive change in our current licensing and educational experience. Why not use this opportunity to reform the DEA-physician/prescriber relationship? 

The educational requirements should be curtailed for those of us who do not provide outpatient narcotic prescriptions even if we use inpatient opioids. Meds with low abuse potential should be rescheduled to minimize who gets caught in the broad net of the education requirement. 

We should reduce overregulation of the legitimate prescribers by lowering, instead of increasing, licensing fees. We should change to a single license number that covers every state. In this digital age, there is no legitimate excuse to prevent this from happening. 

After all, the settlements from opioid manufacturers and distributors will in time total $50 billion. It seems that at least some of the responsibilities of the DEA could shift to states, cities, and towns. 

My friend Siamak Karimian, MD, who provides locum services in multiple states, pays for seven active DEA licenses every 3 years. He pointed out the hypocrisy in the current regulatory system: “It’s funny that you can have only one DEA or state license and work for the government in all other states or territories with no limits, including the VA, Indian healthcare systems, or prison systems.”

All other prescribers require a separate DEA number for every state. Ultimately, you’d think tracking prescriptions for a single DEA number should be far simpler than tracking someone with seven. 

Competent physicians not guilty of criminal overprescribing seem to be the last to be considered in nearly every healthcare endeavor these days. It would be refreshing if they would reduce our fees and prevent this waste of our time. 

And while we are at it, perhaps a more fitting punishment is due for Richard Sackler and all the Purdue Pharma–affiliated family members. The Sacklers will pay out $6 billion in exchange for immunity against civil litigation. That doesn’t seem like much when they are worth $11 billion. 

Perhaps they should be made to take an 8-hour course on opioid prescribing, annually and in perpetuity. Let’s see them complete a few quizlets and sit through screens of instruction on how to administer Naloxone. Of course, that would be a mild punishment for those who manufactured a drug that killed hundreds of thousands. But it would be a start. 
 

Dr. Walton-Shirley, a clinical cardiologist in Nashville, Tennessee, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Despite an expanding arsenal of disease-modifying antirheumatic drugs (DMARDs), many patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) still struggle to reach remission even after trying multiple advanced treatments.

Now, international groups of experts are working to better define these “difficult-to-treat” patients to both inform care and improve selection of participants for future clinical trials.

“The idea is rather simple, and the need is relatively ubiquitous,” Denis Poddubnyy, MD, of the Charité – Universitätsmedizin Berlin and the German Rheumatism Research Center Berlin, both in Berlin, Germany, said in an interview. He is the co-primary investigator for the ongoing Assessment of SpondyloArthritis International Society (ASAS) project to develop a consensus definition of difficult-to-treat axSpA.

According to ASAS, only 40%-50% of patients with axSpA achieve a 40% improvement in ASAS response criteria (ASAS40), and few (10%-20%) achieve remission in the first 4-6 months of treatment.

Multiple Reasons for Nonresponse

“While the term difficult-to-treat can refer to refractory disease, that is not the only reason why a patient might not be responding to medication. In fact, it’s likely that truly biologically refractory disease makes up only a fraction of cases that respond inadequately to treatment,” said Shikha Singla, MD, who directs the psoriatic arthritis program at the Medical College of Wisconsin in Milwaukee. She is also involved with the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) initiative to define Difficult-to-Treat and Complex-to-Manage PsA.

Medical College of Wisconsin

“Apart from the persistent articular and periarticular inflammation, there could be multiple noninflammatory factors that may be contributing to this treatment-resistant disease, including comorbid conditions such as obesity, cardiovascular disease, fibromyalgia, and even social factors such as limited access to medications,” she told this news organization. “Given these complexities, it is a matter of supreme importance to recognize and carefully delineate the elements that contribute to treatment refractory disease: Is it truly the inflammation, or are there noninflammatory components that are causing the treatment failure, or a combination of the two?”

Other contributing factors could be depression, hypersensitization, and comorbidities that prevent certain treatment approaches, added Fabian Proft, MD, also of Charité – Universitätsmedizin Berlin. Dr. Proft discussed these difficult-to-treat definition efforts at the recent Spondyloarthritis Research and Treatment Network (SPARTAN) annual meeting held in Cleveland. Patients also might not be taking their medication regularly and may be seeking alternative medicine approaches, he said.

Dr. Proft

The Definitions

Terminology for these two groups can vary by professional society. The European Alliance of Associations for Rheumatology (EULAR) published a definition for “difficult-to-treat” rheumatoid arthritis (RA) that includes cases with “both inflammatory activity and/or noninflammatory complaints.”

The definition includes three criteria:

1) Treatment according to EULAR recommendation and failure of at least two biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated)

2) Signs suggestive of active/progressive disease, including at least one of the following:

• Moderate disease activity (according to validated composite measures including joint counts)
• Signs (including acute phase reactants and imaging) and/or symptoms suggestive of active disease, whether joint-related or other
• Inability to taper glucocorticoid treatment
• Rapid radiographic progression (with or without signs of active disease)
• RA symptoms that are causing a reduction in quality of life

3) Symptom/sign management perceived as problematic by the rheumatologist or the patient

All three criteria must be met.

Both GRAPPA and ASAS plan to use the term “difficult-to-treat” or “treatment refractory” to describe true biologically refractory inflammatory disease and are categorizing the larger, heterogeneous group of nonresponders as “difficult-to-manage” (ASAS) or “complex-to-manage” (GRAPPA).

According to Dr. Poddubnyy, the agreed ASAS definition of difficult-to-manage has several similarities with EULAR’s RA definition, including three pillars:

• Treatment according to existing recommendations and failure of at least two different bDMARDs or tsDMARDs with different mechanisms
• Having signs and symptoms of disease (measured by high disease activity by certain disease activity indexes, persistently elevated C-reactive protein, inflammation on MRI, or rapid radiographic spinal progression)
• Symptoms/signs of disease that are considered problematic by the provider or patient

The definition was approved in January, and the manuscript is in the works, Dr. Poddubnyy said.

The GRAPPA project on PsA is still in its early stages, which so far has included a comprehensive literature review as well as a survey of GRAPPA members across 47 countries. The group is generally in agreement that two separate definitions for nonresponse to treatment are necessary, and that the “difficult-to-treat” definition — which identifies true refractory disease — should include objective signs of inflammation, Dr. Singla said.
 

Looking Forward

The next step of the ASAS project is to “define the pathway” from difficult-to-manage axSpA to treatment refractory disease, Dr. Poddubnyy said.

“What should be ruled out in order to exclude so-called noninflammatory causes of pain?” he continued. “It will require some Delphi exercises and [a] consensus approach.”

Proft anticipates that this treatment refractory definition in both axSpA and PsA will be most useful in research, rather than clinical practice.

“It is really important to have unified definition criteria to shape as homogeneous a cohort as possible,” he said, for future clinical trials in this population.

On the other hand, the complex/difficult-to-manage definition may be more useful for clinical practice, Dr. Proft thought.

“If you see a patient not responding to treatment, the easiest thing you can do would be to change treatment,” like swapping one biologic for another, Dr. Poddubnyy added, “but this would not be the right approach in every patient.” One goal of these initiatives is to give guidance on “what things should be looked after or excluded before you conclude this is biological [nonresponse],” he said.

Dr. Singla consults for AbbVie, Janssen, and UCB and received research funding from Eli Lilly. Dr. Poddubnyy disclosed serving as a speaker, consultant, and/or research grant recipient for multiple companies including AbbVie, Lilly, Merck Sharp and Dohme, Novartis, Pfizer, GlaxoSmithKline, Novartis, and UCB. Dr. Proft reported receiving research grants, consultant fees, or support for attending meetings and/or travel from Amgen, AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Medscape Medical News, Galapagos, and Hexal. Dr. Proft also participants on a data safety monitoring board or advisory board for AbbVie, Celgene, Janssen, Novartis, and UCB.

A version of this article appeared on Medscape.com.

Despite an expanding arsenal of disease-modifying antirheumatic drugs (DMARDs), many patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) still struggle to reach remission even after trying multiple advanced treatments.

Now, international groups of experts are working to better define these “difficult-to-treat” patients to both inform care and improve selection of participants for future clinical trials.

“The idea is rather simple, and the need is relatively ubiquitous,” Denis Poddubnyy, MD, of the Charité – Universitätsmedizin Berlin and the German Rheumatism Research Center Berlin, both in Berlin, Germany, said in an interview. He is the co-primary investigator for the ongoing Assessment of SpondyloArthritis International Society (ASAS) project to develop a consensus definition of difficult-to-treat axSpA.

According to ASAS, only 40%-50% of patients with axSpA achieve a 40% improvement in ASAS response criteria (ASAS40), and few (10%-20%) achieve remission in the first 4-6 months of treatment.

Multiple Reasons for Nonresponse

“While the term difficult-to-treat can refer to refractory disease, that is not the only reason why a patient might not be responding to medication. In fact, it’s likely that truly biologically refractory disease makes up only a fraction of cases that respond inadequately to treatment,” said Shikha Singla, MD, who directs the psoriatic arthritis program at the Medical College of Wisconsin in Milwaukee. She is also involved with the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) initiative to define Difficult-to-Treat and Complex-to-Manage PsA.

Medical College of Wisconsin

“Apart from the persistent articular and periarticular inflammation, there could be multiple noninflammatory factors that may be contributing to this treatment-resistant disease, including comorbid conditions such as obesity, cardiovascular disease, fibromyalgia, and even social factors such as limited access to medications,” she told this news organization. “Given these complexities, it is a matter of supreme importance to recognize and carefully delineate the elements that contribute to treatment refractory disease: Is it truly the inflammation, or are there noninflammatory components that are causing the treatment failure, or a combination of the two?”

Other contributing factors could be depression, hypersensitization, and comorbidities that prevent certain treatment approaches, added Fabian Proft, MD, also of Charité – Universitätsmedizin Berlin. Dr. Proft discussed these difficult-to-treat definition efforts at the recent Spondyloarthritis Research and Treatment Network (SPARTAN) annual meeting held in Cleveland. Patients also might not be taking their medication regularly and may be seeking alternative medicine approaches, he said.

Dr. Proft

The Definitions

Terminology for these two groups can vary by professional society. The European Alliance of Associations for Rheumatology (EULAR) published a definition for “difficult-to-treat” rheumatoid arthritis (RA) that includes cases with “both inflammatory activity and/or noninflammatory complaints.”

The definition includes three criteria:

1) Treatment according to EULAR recommendation and failure of at least two biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated)

2) Signs suggestive of active/progressive disease, including at least one of the following:

• Moderate disease activity (according to validated composite measures including joint counts)
• Signs (including acute phase reactants and imaging) and/or symptoms suggestive of active disease, whether joint-related or other
• Inability to taper glucocorticoid treatment
• Rapid radiographic progression (with or without signs of active disease)
• RA symptoms that are causing a reduction in quality of life

3) Symptom/sign management perceived as problematic by the rheumatologist or the patient

All three criteria must be met.

Both GRAPPA and ASAS plan to use the term “difficult-to-treat” or “treatment refractory” to describe true biologically refractory inflammatory disease and are categorizing the larger, heterogeneous group of nonresponders as “difficult-to-manage” (ASAS) or “complex-to-manage” (GRAPPA).

According to Dr. Poddubnyy, the agreed ASAS definition of difficult-to-manage has several similarities with EULAR’s RA definition, including three pillars:

• Treatment according to existing recommendations and failure of at least two different bDMARDs or tsDMARDs with different mechanisms
• Having signs and symptoms of disease (measured by high disease activity by certain disease activity indexes, persistently elevated C-reactive protein, inflammation on MRI, or rapid radiographic spinal progression)
• Symptoms/signs of disease that are considered problematic by the provider or patient

The definition was approved in January, and the manuscript is in the works, Dr. Poddubnyy said.

The GRAPPA project on PsA is still in its early stages, which so far has included a comprehensive literature review as well as a survey of GRAPPA members across 47 countries. The group is generally in agreement that two separate definitions for nonresponse to treatment are necessary, and that the “difficult-to-treat” definition — which identifies true refractory disease — should include objective signs of inflammation, Dr. Singla said.
 

Looking Forward

The next step of the ASAS project is to “define the pathway” from difficult-to-manage axSpA to treatment refractory disease, Dr. Poddubnyy said.

“What should be ruled out in order to exclude so-called noninflammatory causes of pain?” he continued. “It will require some Delphi exercises and [a] consensus approach.”

Proft anticipates that this treatment refractory definition in both axSpA and PsA will be most useful in research, rather than clinical practice.

“It is really important to have unified definition criteria to shape as homogeneous a cohort as possible,” he said, for future clinical trials in this population.

On the other hand, the complex/difficult-to-manage definition may be more useful for clinical practice, Dr. Proft thought.

“If you see a patient not responding to treatment, the easiest thing you can do would be to change treatment,” like swapping one biologic for another, Dr. Poddubnyy added, “but this would not be the right approach in every patient.” One goal of these initiatives is to give guidance on “what things should be looked after or excluded before you conclude this is biological [nonresponse],” he said.

Dr. Singla consults for AbbVie, Janssen, and UCB and received research funding from Eli Lilly. Dr. Poddubnyy disclosed serving as a speaker, consultant, and/or research grant recipient for multiple companies including AbbVie, Lilly, Merck Sharp and Dohme, Novartis, Pfizer, GlaxoSmithKline, Novartis, and UCB. Dr. Proft reported receiving research grants, consultant fees, or support for attending meetings and/or travel from Amgen, AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Medscape Medical News, Galapagos, and Hexal. Dr. Proft also participants on a data safety monitoring board or advisory board for AbbVie, Celgene, Janssen, Novartis, and UCB.

A version of this article appeared on Medscape.com.

Despite an expanding arsenal of disease-modifying antirheumatic drugs (DMARDs), many patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) still struggle to reach remission even after trying multiple advanced treatments.

Now, international groups of experts are working to better define these “difficult-to-treat” patients to both inform care and improve selection of participants for future clinical trials.

“The idea is rather simple, and the need is relatively ubiquitous,” Denis Poddubnyy, MD, of the Charité – Universitätsmedizin Berlin and the German Rheumatism Research Center Berlin, both in Berlin, Germany, said in an interview. He is the co-primary investigator for the ongoing Assessment of SpondyloArthritis International Society (ASAS) project to develop a consensus definition of difficult-to-treat axSpA.

According to ASAS, only 40%-50% of patients with axSpA achieve a 40% improvement in ASAS response criteria (ASAS40), and few (10%-20%) achieve remission in the first 4-6 months of treatment.

Multiple Reasons for Nonresponse

“While the term difficult-to-treat can refer to refractory disease, that is not the only reason why a patient might not be responding to medication. In fact, it’s likely that truly biologically refractory disease makes up only a fraction of cases that respond inadequately to treatment,” said Shikha Singla, MD, who directs the psoriatic arthritis program at the Medical College of Wisconsin in Milwaukee. She is also involved with the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) initiative to define Difficult-to-Treat and Complex-to-Manage PsA.

Medical College of Wisconsin

“Apart from the persistent articular and periarticular inflammation, there could be multiple noninflammatory factors that may be contributing to this treatment-resistant disease, including comorbid conditions such as obesity, cardiovascular disease, fibromyalgia, and even social factors such as limited access to medications,” she told this news organization. “Given these complexities, it is a matter of supreme importance to recognize and carefully delineate the elements that contribute to treatment refractory disease: Is it truly the inflammation, or are there noninflammatory components that are causing the treatment failure, or a combination of the two?”

Other contributing factors could be depression, hypersensitization, and comorbidities that prevent certain treatment approaches, added Fabian Proft, MD, also of Charité – Universitätsmedizin Berlin. Dr. Proft discussed these difficult-to-treat definition efforts at the recent Spondyloarthritis Research and Treatment Network (SPARTAN) annual meeting held in Cleveland. Patients also might not be taking their medication regularly and may be seeking alternative medicine approaches, he said.

Dr. Proft

The Definitions

Terminology for these two groups can vary by professional society. The European Alliance of Associations for Rheumatology (EULAR) published a definition for “difficult-to-treat” rheumatoid arthritis (RA) that includes cases with “both inflammatory activity and/or noninflammatory complaints.”

The definition includes three criteria:

1) Treatment according to EULAR recommendation and failure of at least two biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated)

2) Signs suggestive of active/progressive disease, including at least one of the following:

• Moderate disease activity (according to validated composite measures including joint counts)
• Signs (including acute phase reactants and imaging) and/or symptoms suggestive of active disease, whether joint-related or other
• Inability to taper glucocorticoid treatment
• Rapid radiographic progression (with or without signs of active disease)
• RA symptoms that are causing a reduction in quality of life

3) Symptom/sign management perceived as problematic by the rheumatologist or the patient

All three criteria must be met.

Both GRAPPA and ASAS plan to use the term “difficult-to-treat” or “treatment refractory” to describe true biologically refractory inflammatory disease and are categorizing the larger, heterogeneous group of nonresponders as “difficult-to-manage” (ASAS) or “complex-to-manage” (GRAPPA).

According to Dr. Poddubnyy, the agreed ASAS definition of difficult-to-manage has several similarities with EULAR’s RA definition, including three pillars:

• Treatment according to existing recommendations and failure of at least two different bDMARDs or tsDMARDs with different mechanisms
• Having signs and symptoms of disease (measured by high disease activity by certain disease activity indexes, persistently elevated C-reactive protein, inflammation on MRI, or rapid radiographic spinal progression)
• Symptoms/signs of disease that are considered problematic by the provider or patient

The definition was approved in January, and the manuscript is in the works, Dr. Poddubnyy said.

The GRAPPA project on PsA is still in its early stages, which so far has included a comprehensive literature review as well as a survey of GRAPPA members across 47 countries. The group is generally in agreement that two separate definitions for nonresponse to treatment are necessary, and that the “difficult-to-treat” definition — which identifies true refractory disease — should include objective signs of inflammation, Dr. Singla said.
 

Looking Forward

The next step of the ASAS project is to “define the pathway” from difficult-to-manage axSpA to treatment refractory disease, Dr. Poddubnyy said.

“What should be ruled out in order to exclude so-called noninflammatory causes of pain?” he continued. “It will require some Delphi exercises and [a] consensus approach.”

Proft anticipates that this treatment refractory definition in both axSpA and PsA will be most useful in research, rather than clinical practice.

“It is really important to have unified definition criteria to shape as homogeneous a cohort as possible,” he said, for future clinical trials in this population.

On the other hand, the complex/difficult-to-manage definition may be more useful for clinical practice, Dr. Proft thought.

“If you see a patient not responding to treatment, the easiest thing you can do would be to change treatment,” like swapping one biologic for another, Dr. Poddubnyy added, “but this would not be the right approach in every patient.” One goal of these initiatives is to give guidance on “what things should be looked after or excluded before you conclude this is biological [nonresponse],” he said.

Dr. Singla consults for AbbVie, Janssen, and UCB and received research funding from Eli Lilly. Dr. Poddubnyy disclosed serving as a speaker, consultant, and/or research grant recipient for multiple companies including AbbVie, Lilly, Merck Sharp and Dohme, Novartis, Pfizer, GlaxoSmithKline, Novartis, and UCB. Dr. Proft reported receiving research grants, consultant fees, or support for attending meetings and/or travel from Amgen, AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Medscape Medical News, Galapagos, and Hexal. Dr. Proft also participants on a data safety monitoring board or advisory board for AbbVie, Celgene, Janssen, Novartis, and UCB.

A version of this article appeared on Medscape.com.

VIENNA — Anti-Ro/SSA antibodies may help predict which patients with systemic sclerosis (SSc) are at a greater risk for interstitial lung disease (ILD) and may serve as a biomarker to guide screening, according to an analysis of data from a large European cohort.

The researchers were led by Blaž Burja, MD, PhD, a physician-scientist at the Center of Experimental Rheumatology, University Hospital Zürich, Switzerland, who reported that anti-Ro/SSA antibodies are a risk factor for ILD, with an odds ratio of 1.24, in patients with SSc.

At the annual European Congress of Rheumatology, he presented the findings of the study that aimed to find out if SSc-nonspecific antibodies might help better risk-stratify patients with SSc, focusing on lung involvement. “Among them, anti-Ro/SSA antibodies have been shown to be associated with interstitial lung disease in different connective tissue diseases,” Dr. Burja pointed out.

“A total of 15% of all patients in the SSc cohort presented with anti-Ro/SSA antibodies, and this subgroup presented with distinct clinical features: Importantly, higher prevalence of ILD and lower DLCO% [diffusing capacity of the lungs for carbon monoxide] in patients with established ILD,” reported Dr. Burja. “However, these anti-Ro/SSA antibodies do not predict ILD progression, death, or overall disease progression.”

Based on the findings, Dr. Burja suggested that these antibodies be incorporated into routine clinical practice to identify patients with SSc who have a high risk for ILD. He noted that “this has specific importance in clinical settings without availability of high-resolution computed tomography (HRCT), where anti-Ro/SSA antibodies could represent an additional biomarker to guide the screening process, in particular, in patients without SSc-specific antibodies.”

Caroline Ospelt, MD, PhD, co-moderator of the session and scientific program chair of EULAR 2024, told this news organization that the study was unique in its approach to studying ILD risk by “looking outside the box, so not just at specific antibodies but whether cross-disease antibodies may have value in stratifying patients and help predict risk of lung involvement and possibly monitor these patients.”

Dr. Ospelt, professor of experimental rheumatology at University Hospital Zürich, who was not involved in the study, noted: “It might also be the case that we could adapt this concept and use these antibodies in other rheumatic diseases, too, not just systemic sclerosis, to predict lung involvement.”
 

Risk-Stratifying With SSc-Nonspecific Antibodies

Dr. Burja explained that despite better stratification of patients with SSc with SSc-specific antibodies, “in clinical practice, we see large heterogeneity, and individual prognosis with regards to outcomes is still unpredictable, so we wanted to know whether by using nonspecific autoantibodies we might be better able to risk-stratify these patients.”

A study population of 4421 with at least one follow-up visit, including 3060 patients with available follow-up serologic data, was drawn from the European Scleroderma Trials and Research group database (n = 22,482). Of these 3060 patients, 461 were positive for anti-Ro/SSA antibodies and 2599 were negative. The researchers analyzed the relationships between baseline characteristics and the development or progression of ILD over 2.7 years of follow-up. Incident, de novo ILD was defined based on its presence on HRCT, and progression was defined by whether the percentage of predicted forced vital capacity (FVC%) dropped ≥ 10%, FVC% dropped 5%-9% in association with a DLCO% drop ≥ 15%, or FVC% dropped > 5%. Deaths from all causes and prognostic factors for the progression of lung fibrosis during follow-up were recorded.
 

High Prevalence of ILD With Anti-Ro/SSA Antibodies in SSc

At baseline, patients with anti-Ro/SSA antibodies were aged 55-56 years, 84%-87% were women, and muscular involvement was present in 18% of patients positive for anti-Ro/SSA antibodies and 12.5% of those who were negative (P < .001). According to HRCT, ILD was present in 56.2% of patients positive for anti-Ro/SSA antibodies and in 47.8% of those who were negative (P = .001). FVC% was 92.5% in patients positive for anti-Ro/SSA antibodies and 95.7% in those who were negative (P = .002). DLCO% was 66.9% in patients positive for anti-Ro/SSA antibodies and 71% in those who were negative (P < .001).

“A total of 15% of all SSc patients presented as positive for anti-Ro/SSA antibodies, and these patients all presented with higher prevalence of SSA-nonspecific antibodies, too: Of note, those with anti-La/SSB and anti-U1/RNP and rheumatoid factor,” Dr. Burja reported.

In patients with anti-U1/RNP autoantibodies, 1% were positive and 4% were negative for anti-Ro/SSA antibodies; in those with anti-La/SSB autoantibodies, 17% were positive and 1% were negative for anti-Ro/SSA antibodies; and in those with rheumatoid factor, 28% were positive and 14% were negative for anti-Ro/SSA antibodies.

Dr. Burja pointed out that the average disease duration in the study cohort at baseline was 7 years, “and at this timepoint, we expect to see some common disease manifestations. Specifically, higher muscular involvement and higher ILD based on HRCT.

“We decided to focus on patients with established ILD at baseline,” said Dr. Burja. “Anti-Ro/SSA-positive patients with established ILD at baseline presented with lower DLCO values at 59% in patients positive for anti-Ro/SSA antibodies and 61% for those who were negative.”

After conducting a multivariable analysis of 14,066 healthcare visits and adjusting for known risk factors for ILD, the researchers concluded that anti-Ro/SSA antibodies are an independent risk factor for ILD, with an odds ratio of 1.24 (95% CI, 1.07-1.44; P = .006). They also determined that anti-Ro/SSA antibodies are a risk factor for lower DLCO values in patients with ILD, with a regression coefficient of −1.93.

The researchers then explored the progression of ILD and overall disease progression and survival during the follow-up period in a longitudinal analysis. “However, anti-Ro/SSA antibodies were not found to predict the progression of ILD,” reported Dr. Burja, adding that this was true regardless of the definition of ILD progression used. “Nor did anti-Ro/SSA antibodies do not predict survival or overall disease progression.”

Dr. Burja pointed out the limitations in his study, including the lack of standardized criteria for all centers to assess anti-Ro/SSA positivity; there was a lack of discrimination between anti-Ro52 and anti-Ro60 subtypes, and there were no standardized applicable criteria to study lung progression in SSc.

Dr. Burja and Dr. Ospelt had no relevant financial disclosures.
 

A version of this article appeared on Medscape.com.

VIENNA — Anti-Ro/SSA antibodies may help predict which patients with systemic sclerosis (SSc) are at a greater risk for interstitial lung disease (ILD) and may serve as a biomarker to guide screening, according to an analysis of data from a large European cohort.

The researchers were led by Blaž Burja, MD, PhD, a physician-scientist at the Center of Experimental Rheumatology, University Hospital Zürich, Switzerland, who reported that anti-Ro/SSA antibodies are a risk factor for ILD, with an odds ratio of 1.24, in patients with SSc.

At the annual European Congress of Rheumatology, he presented the findings of the study that aimed to find out if SSc-nonspecific antibodies might help better risk-stratify patients with SSc, focusing on lung involvement. “Among them, anti-Ro/SSA antibodies have been shown to be associated with interstitial lung disease in different connective tissue diseases,” Dr. Burja pointed out.

“A total of 15% of all patients in the SSc cohort presented with anti-Ro/SSA antibodies, and this subgroup presented with distinct clinical features: Importantly, higher prevalence of ILD and lower DLCO% [diffusing capacity of the lungs for carbon monoxide] in patients with established ILD,” reported Dr. Burja. “However, these anti-Ro/SSA antibodies do not predict ILD progression, death, or overall disease progression.”

Based on the findings, Dr. Burja suggested that these antibodies be incorporated into routine clinical practice to identify patients with SSc who have a high risk for ILD. He noted that “this has specific importance in clinical settings without availability of high-resolution computed tomography (HRCT), where anti-Ro/SSA antibodies could represent an additional biomarker to guide the screening process, in particular, in patients without SSc-specific antibodies.”

Caroline Ospelt, MD, PhD, co-moderator of the session and scientific program chair of EULAR 2024, told this news organization that the study was unique in its approach to studying ILD risk by “looking outside the box, so not just at specific antibodies but whether cross-disease antibodies may have value in stratifying patients and help predict risk of lung involvement and possibly monitor these patients.”

Dr. Ospelt, professor of experimental rheumatology at University Hospital Zürich, who was not involved in the study, noted: “It might also be the case that we could adapt this concept and use these antibodies in other rheumatic diseases, too, not just systemic sclerosis, to predict lung involvement.”
 

Risk-Stratifying With SSc-Nonspecific Antibodies

Dr. Burja explained that despite better stratification of patients with SSc with SSc-specific antibodies, “in clinical practice, we see large heterogeneity, and individual prognosis with regards to outcomes is still unpredictable, so we wanted to know whether by using nonspecific autoantibodies we might be better able to risk-stratify these patients.”

A study population of 4421 with at least one follow-up visit, including 3060 patients with available follow-up serologic data, was drawn from the European Scleroderma Trials and Research group database (n = 22,482). Of these 3060 patients, 461 were positive for anti-Ro/SSA antibodies and 2599 were negative. The researchers analyzed the relationships between baseline characteristics and the development or progression of ILD over 2.7 years of follow-up. Incident, de novo ILD was defined based on its presence on HRCT, and progression was defined by whether the percentage of predicted forced vital capacity (FVC%) dropped ≥ 10%, FVC% dropped 5%-9% in association with a DLCO% drop ≥ 15%, or FVC% dropped > 5%. Deaths from all causes and prognostic factors for the progression of lung fibrosis during follow-up were recorded.
 

High Prevalence of ILD With Anti-Ro/SSA Antibodies in SSc

At baseline, patients with anti-Ro/SSA antibodies were aged 55-56 years, 84%-87% were women, and muscular involvement was present in 18% of patients positive for anti-Ro/SSA antibodies and 12.5% of those who were negative (P < .001). According to HRCT, ILD was present in 56.2% of patients positive for anti-Ro/SSA antibodies and in 47.8% of those who were negative (P = .001). FVC% was 92.5% in patients positive for anti-Ro/SSA antibodies and 95.7% in those who were negative (P = .002). DLCO% was 66.9% in patients positive for anti-Ro/SSA antibodies and 71% in those who were negative (P < .001).

“A total of 15% of all SSc patients presented as positive for anti-Ro/SSA antibodies, and these patients all presented with higher prevalence of SSA-nonspecific antibodies, too: Of note, those with anti-La/SSB and anti-U1/RNP and rheumatoid factor,” Dr. Burja reported.

In patients with anti-U1/RNP autoantibodies, 1% were positive and 4% were negative for anti-Ro/SSA antibodies; in those with anti-La/SSB autoantibodies, 17% were positive and 1% were negative for anti-Ro/SSA antibodies; and in those with rheumatoid factor, 28% were positive and 14% were negative for anti-Ro/SSA antibodies.

Dr. Burja pointed out that the average disease duration in the study cohort at baseline was 7 years, “and at this timepoint, we expect to see some common disease manifestations. Specifically, higher muscular involvement and higher ILD based on HRCT.

“We decided to focus on patients with established ILD at baseline,” said Dr. Burja. “Anti-Ro/SSA-positive patients with established ILD at baseline presented with lower DLCO values at 59% in patients positive for anti-Ro/SSA antibodies and 61% for those who were negative.”

After conducting a multivariable analysis of 14,066 healthcare visits and adjusting for known risk factors for ILD, the researchers concluded that anti-Ro/SSA antibodies are an independent risk factor for ILD, with an odds ratio of 1.24 (95% CI, 1.07-1.44; P = .006). They also determined that anti-Ro/SSA antibodies are a risk factor for lower DLCO values in patients with ILD, with a regression coefficient of −1.93.

The researchers then explored the progression of ILD and overall disease progression and survival during the follow-up period in a longitudinal analysis. “However, anti-Ro/SSA antibodies were not found to predict the progression of ILD,” reported Dr. Burja, adding that this was true regardless of the definition of ILD progression used. “Nor did anti-Ro/SSA antibodies do not predict survival or overall disease progression.”

Dr. Burja pointed out the limitations in his study, including the lack of standardized criteria for all centers to assess anti-Ro/SSA positivity; there was a lack of discrimination between anti-Ro52 and anti-Ro60 subtypes, and there were no standardized applicable criteria to study lung progression in SSc.

Dr. Burja and Dr. Ospelt had no relevant financial disclosures.
 

A version of this article appeared on Medscape.com.

VIENNA — Anti-Ro/SSA antibodies may help predict which patients with systemic sclerosis (SSc) are at a greater risk for interstitial lung disease (ILD) and may serve as a biomarker to guide screening, according to an analysis of data from a large European cohort.

The researchers were led by Blaž Burja, MD, PhD, a physician-scientist at the Center of Experimental Rheumatology, University Hospital Zürich, Switzerland, who reported that anti-Ro/SSA antibodies are a risk factor for ILD, with an odds ratio of 1.24, in patients with SSc.

At the annual European Congress of Rheumatology, he presented the findings of the study that aimed to find out if SSc-nonspecific antibodies might help better risk-stratify patients with SSc, focusing on lung involvement. “Among them, anti-Ro/SSA antibodies have been shown to be associated with interstitial lung disease in different connective tissue diseases,” Dr. Burja pointed out.

“A total of 15% of all patients in the SSc cohort presented with anti-Ro/SSA antibodies, and this subgroup presented with distinct clinical features: Importantly, higher prevalence of ILD and lower DLCO% [diffusing capacity of the lungs for carbon monoxide] in patients with established ILD,” reported Dr. Burja. “However, these anti-Ro/SSA antibodies do not predict ILD progression, death, or overall disease progression.”

Based on the findings, Dr. Burja suggested that these antibodies be incorporated into routine clinical practice to identify patients with SSc who have a high risk for ILD. He noted that “this has specific importance in clinical settings without availability of high-resolution computed tomography (HRCT), where anti-Ro/SSA antibodies could represent an additional biomarker to guide the screening process, in particular, in patients without SSc-specific antibodies.”

Caroline Ospelt, MD, PhD, co-moderator of the session and scientific program chair of EULAR 2024, told this news organization that the study was unique in its approach to studying ILD risk by “looking outside the box, so not just at specific antibodies but whether cross-disease antibodies may have value in stratifying patients and help predict risk of lung involvement and possibly monitor these patients.”

Dr. Ospelt, professor of experimental rheumatology at University Hospital Zürich, who was not involved in the study, noted: “It might also be the case that we could adapt this concept and use these antibodies in other rheumatic diseases, too, not just systemic sclerosis, to predict lung involvement.”
 

Risk-Stratifying With SSc-Nonspecific Antibodies

Dr. Burja explained that despite better stratification of patients with SSc with SSc-specific antibodies, “in clinical practice, we see large heterogeneity, and individual prognosis with regards to outcomes is still unpredictable, so we wanted to know whether by using nonspecific autoantibodies we might be better able to risk-stratify these patients.”

A study population of 4421 with at least one follow-up visit, including 3060 patients with available follow-up serologic data, was drawn from the European Scleroderma Trials and Research group database (n = 22,482). Of these 3060 patients, 461 were positive for anti-Ro/SSA antibodies and 2599 were negative. The researchers analyzed the relationships between baseline characteristics and the development or progression of ILD over 2.7 years of follow-up. Incident, de novo ILD was defined based on its presence on HRCT, and progression was defined by whether the percentage of predicted forced vital capacity (FVC%) dropped ≥ 10%, FVC% dropped 5%-9% in association with a DLCO% drop ≥ 15%, or FVC% dropped > 5%. Deaths from all causes and prognostic factors for the progression of lung fibrosis during follow-up were recorded.
 

High Prevalence of ILD With Anti-Ro/SSA Antibodies in SSc

At baseline, patients with anti-Ro/SSA antibodies were aged 55-56 years, 84%-87% were women, and muscular involvement was present in 18% of patients positive for anti-Ro/SSA antibodies and 12.5% of those who were negative (P < .001). According to HRCT, ILD was present in 56.2% of patients positive for anti-Ro/SSA antibodies and in 47.8% of those who were negative (P = .001). FVC% was 92.5% in patients positive for anti-Ro/SSA antibodies and 95.7% in those who were negative (P = .002). DLCO% was 66.9% in patients positive for anti-Ro/SSA antibodies and 71% in those who were negative (P < .001).

“A total of 15% of all SSc patients presented as positive for anti-Ro/SSA antibodies, and these patients all presented with higher prevalence of SSA-nonspecific antibodies, too: Of note, those with anti-La/SSB and anti-U1/RNP and rheumatoid factor,” Dr. Burja reported.

In patients with anti-U1/RNP autoantibodies, 1% were positive and 4% were negative for anti-Ro/SSA antibodies; in those with anti-La/SSB autoantibodies, 17% were positive and 1% were negative for anti-Ro/SSA antibodies; and in those with rheumatoid factor, 28% were positive and 14% were negative for anti-Ro/SSA antibodies.

Dr. Burja pointed out that the average disease duration in the study cohort at baseline was 7 years, “and at this timepoint, we expect to see some common disease manifestations. Specifically, higher muscular involvement and higher ILD based on HRCT.

“We decided to focus on patients with established ILD at baseline,” said Dr. Burja. “Anti-Ro/SSA-positive patients with established ILD at baseline presented with lower DLCO values at 59% in patients positive for anti-Ro/SSA antibodies and 61% for those who were negative.”

After conducting a multivariable analysis of 14,066 healthcare visits and adjusting for known risk factors for ILD, the researchers concluded that anti-Ro/SSA antibodies are an independent risk factor for ILD, with an odds ratio of 1.24 (95% CI, 1.07-1.44; P = .006). They also determined that anti-Ro/SSA antibodies are a risk factor for lower DLCO values in patients with ILD, with a regression coefficient of −1.93.

The researchers then explored the progression of ILD and overall disease progression and survival during the follow-up period in a longitudinal analysis. “However, anti-Ro/SSA antibodies were not found to predict the progression of ILD,” reported Dr. Burja, adding that this was true regardless of the definition of ILD progression used. “Nor did anti-Ro/SSA antibodies do not predict survival or overall disease progression.”

Dr. Burja pointed out the limitations in his study, including the lack of standardized criteria for all centers to assess anti-Ro/SSA positivity; there was a lack of discrimination between anti-Ro52 and anti-Ro60 subtypes, and there were no standardized applicable criteria to study lung progression in SSc.

Dr. Burja and Dr. Ospelt had no relevant financial disclosures.
 

A version of this article appeared on Medscape.com.

VIENNA — In patients with rheumatoid arthritis (RA), Janus kinase inhibitors (JAKi) are associated with a substantially greater risk for herpes zoster, but the risk for other types of infections is about the same and often numerically lower relative to biologic disease-modifying antirheumatic drugs (bDMARDs), according to new data from the JAK-pot study.

“In the real world, we found no significantly greater risk of serious or nonserious infections, with the exception of herpes zoster,” said Romain Aymon, a statistician in the Department of Rheumatology at the University Hospital of Geneva, Switzerland.

Ted Bosworth/Medscape Medical News

This finding is the latest analysis generated by JAK-pot, a collaboration of 20 national registries to answer real-world questions about the efficacy and safety of JAKi in rheumatic diseases. These data have already been used to address such issues as relative rates of discontinuation for JAKi vs bDMARDs and to compare outcomes of RA patients who are switched to a bDMARD vs those who are cycled to another JAKi.

The main conclusion — that JAKi, relative to bDMARDs for RA, is associated with an increased risk for herpes zoster but not other types of infections — is not a surprise, according to Floris A. van Gaalen, MD, PhD, a clinician and researcher in the Department of Rheumatology, Leiden University in the Netherlands.

“There are a number of risks with JAK inhibitors that have generated concern, but I think most clinicians are aware that they should be warning patients about herpes zoster,” said Dr. van Gaalen, who was not involved in the study. He believes the risk is sufficient to warrant a discussion with patients about taking the herpes zoster vaccine prior to treatment.

Relative Risk for Infection on JAKi Is Unclear

Although the greater risk for herpes zoster with JAKi vs bDMARDs is well established, the relative risk for other types of infections has been unclear, according to Mr. Aymon. One reason is that some, but not all, of the initial pivotal trials and safety studies associated JAKi with an increased risk for opportunistic infections, Mr. Aymon said.

The JAK-pot data, presented at the annual European Congress of Rheumatology, provide real-world data that shed light on this controversy, Mr. Aymon said.

Of the 20 national registries now providing data to JAK-pot, only 14 were included in this analysis. The study required data on infection rates from the time that JAKi became commercially available, which narrowed the data pool.

For this analysis, JAKi, which included tofacitinib (Xeljanz), baricitinib (Olumiant), upadacitinib (Rinvoq), and filgotinib (Jyseleca), were compared separately and together with two groups of bDMARDs. One consisted of the tumor necrosis factor inhibitors (TNFi), infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab. The other was composed of bDMARDs with other modes of action (OMA). This group included abatacept, rituximab, sarilumab, and tocilizumab.
 

More Than 50,000 Exposures Included in Analysis

From the pooled registry, data were gathered from 13,374 courses of JAKi, 25,049 courses of TNFi, and 16,482 courses of OMA. There were some differences between these groups, including a significantly lower median age for those in the JAKi pool (57.1 years vs 58.3 and 60.5 years for TNFi and OMA, respectively) and median disease duration (8.3 years vs 11.0 and 11.9 years, respectively).

A greater proportion of patients on TNFi were naive to therapy (44.6%), compared with either JAKi (20.2%) or OMA (16.1%). More patients in the TNFi pool (60.0%) were also on concomitant therapy than those in the JAKi pool (49.5%) or the OMA pool (51.9%).

Other characteristics such as disease activity, body mass index, and percentage of smokers were comparable.

When TNFi was used as the reference, there were no significant differences in the rate of all infections, the rate of all infections excluding herpes zoster, and all serious infections. In all three groups, the incidence rates were numerically but not significantly lower in patients on JAKi vs OMA. With the exception of serious infections, for which the adjusted incidence of JAKi was 0.99 relative to TNFi, both JAKi and OMA had numerically higher incidence rate ratios than TNFi.
 

Herpes Zoster Risk on JAKi Is > Twofold Higher

Because the CIs overlapped in all cases, none of the differences were significant. The exception was herpes zoster. The 1.07 incidence rate ratio for OMA was not significantly different than the TNFi reference, but the 2.27 rate ratio for JAKi far exceeded either of the other two comparators (95% CI, 1.17-3.02).

In a separate analysis of patients at least 55 years of age with at least one cardiovascular risk factor, the numerical differences between groups were narrower and thus did not reach statistical significance, even for herpes zoster. Although the herpes zoster rate ratio was 1.62 for JAKi vs 1.23 for OMA (TNFi as the reference was 1.0), the CI for JAKi (0.86-3.03) overlapped both.

Based on a Poisson regression analysis, this study took into account a wide variety of variables, including age, disease activity, comorbidities, and tobacco use, Mr. Aymon said. He noted that the analyses were performed on data from each registry as well as with the pooled data, and the data were reasonably consistent.

Initially, the investigators had planned to evaluate differences between therapy groups, if any, for COVID-19 infection, but differences in the availability and use of vaccinations among the countries where the registries were maintained made this analysis too complicated to conduct.

Mr. Aymon reported no potential conflicts of interest, but some coauthors reported financial relationships with manufacturers of both bDMARDs and JAKi. Dr. van Gaalen reported financial relationships with AbbVie, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, and UCB.

A version of this article appeared on Medscape.com.

VIENNA — In patients with rheumatoid arthritis (RA), Janus kinase inhibitors (JAKi) are associated with a substantially greater risk for herpes zoster, but the risk for other types of infections is about the same and often numerically lower relative to biologic disease-modifying antirheumatic drugs (bDMARDs), according to new data from the JAK-pot study.

“In the real world, we found no significantly greater risk of serious or nonserious infections, with the exception of herpes zoster,” said Romain Aymon, a statistician in the Department of Rheumatology at the University Hospital of Geneva, Switzerland.

Ted Bosworth/Medscape Medical News

This finding is the latest analysis generated by JAK-pot, a collaboration of 20 national registries to answer real-world questions about the efficacy and safety of JAKi in rheumatic diseases. These data have already been used to address such issues as relative rates of discontinuation for JAKi vs bDMARDs and to compare outcomes of RA patients who are switched to a bDMARD vs those who are cycled to another JAKi.

The main conclusion — that JAKi, relative to bDMARDs for RA, is associated with an increased risk for herpes zoster but not other types of infections — is not a surprise, according to Floris A. van Gaalen, MD, PhD, a clinician and researcher in the Department of Rheumatology, Leiden University in the Netherlands.

“There are a number of risks with JAK inhibitors that have generated concern, but I think most clinicians are aware that they should be warning patients about herpes zoster,” said Dr. van Gaalen, who was not involved in the study. He believes the risk is sufficient to warrant a discussion with patients about taking the herpes zoster vaccine prior to treatment.

Relative Risk for Infection on JAKi Is Unclear

Although the greater risk for herpes zoster with JAKi vs bDMARDs is well established, the relative risk for other types of infections has been unclear, according to Mr. Aymon. One reason is that some, but not all, of the initial pivotal trials and safety studies associated JAKi with an increased risk for opportunistic infections, Mr. Aymon said.

The JAK-pot data, presented at the annual European Congress of Rheumatology, provide real-world data that shed light on this controversy, Mr. Aymon said.

Of the 20 national registries now providing data to JAK-pot, only 14 were included in this analysis. The study required data on infection rates from the time that JAKi became commercially available, which narrowed the data pool.

For this analysis, JAKi, which included tofacitinib (Xeljanz), baricitinib (Olumiant), upadacitinib (Rinvoq), and filgotinib (Jyseleca), were compared separately and together with two groups of bDMARDs. One consisted of the tumor necrosis factor inhibitors (TNFi), infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab. The other was composed of bDMARDs with other modes of action (OMA). This group included abatacept, rituximab, sarilumab, and tocilizumab.
 

More Than 50,000 Exposures Included in Analysis

From the pooled registry, data were gathered from 13,374 courses of JAKi, 25,049 courses of TNFi, and 16,482 courses of OMA. There were some differences between these groups, including a significantly lower median age for those in the JAKi pool (57.1 years vs 58.3 and 60.5 years for TNFi and OMA, respectively) and median disease duration (8.3 years vs 11.0 and 11.9 years, respectively).

A greater proportion of patients on TNFi were naive to therapy (44.6%), compared with either JAKi (20.2%) or OMA (16.1%). More patients in the TNFi pool (60.0%) were also on concomitant therapy than those in the JAKi pool (49.5%) or the OMA pool (51.9%).

Other characteristics such as disease activity, body mass index, and percentage of smokers were comparable.

When TNFi was used as the reference, there were no significant differences in the rate of all infections, the rate of all infections excluding herpes zoster, and all serious infections. In all three groups, the incidence rates were numerically but not significantly lower in patients on JAKi vs OMA. With the exception of serious infections, for which the adjusted incidence of JAKi was 0.99 relative to TNFi, both JAKi and OMA had numerically higher incidence rate ratios than TNFi.
 

Herpes Zoster Risk on JAKi Is > Twofold Higher

Because the CIs overlapped in all cases, none of the differences were significant. The exception was herpes zoster. The 1.07 incidence rate ratio for OMA was not significantly different than the TNFi reference, but the 2.27 rate ratio for JAKi far exceeded either of the other two comparators (95% CI, 1.17-3.02).

In a separate analysis of patients at least 55 years of age with at least one cardiovascular risk factor, the numerical differences between groups were narrower and thus did not reach statistical significance, even for herpes zoster. Although the herpes zoster rate ratio was 1.62 for JAKi vs 1.23 for OMA (TNFi as the reference was 1.0), the CI for JAKi (0.86-3.03) overlapped both.

Based on a Poisson regression analysis, this study took into account a wide variety of variables, including age, disease activity, comorbidities, and tobacco use, Mr. Aymon said. He noted that the analyses were performed on data from each registry as well as with the pooled data, and the data were reasonably consistent.

Initially, the investigators had planned to evaluate differences between therapy groups, if any, for COVID-19 infection, but differences in the availability and use of vaccinations among the countries where the registries were maintained made this analysis too complicated to conduct.

Mr. Aymon reported no potential conflicts of interest, but some coauthors reported financial relationships with manufacturers of both bDMARDs and JAKi. Dr. van Gaalen reported financial relationships with AbbVie, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, and UCB.

A version of this article appeared on Medscape.com.

VIENNA — In patients with rheumatoid arthritis (RA), Janus kinase inhibitors (JAKi) are associated with a substantially greater risk for herpes zoster, but the risk for other types of infections is about the same and often numerically lower relative to biologic disease-modifying antirheumatic drugs (bDMARDs), according to new data from the JAK-pot study.

“In the real world, we found no significantly greater risk of serious or nonserious infections, with the exception of herpes zoster,” said Romain Aymon, a statistician in the Department of Rheumatology at the University Hospital of Geneva, Switzerland.

Ted Bosworth/Medscape Medical News

This finding is the latest analysis generated by JAK-pot, a collaboration of 20 national registries to answer real-world questions about the efficacy and safety of JAKi in rheumatic diseases. These data have already been used to address such issues as relative rates of discontinuation for JAKi vs bDMARDs and to compare outcomes of RA patients who are switched to a bDMARD vs those who are cycled to another JAKi.

The main conclusion — that JAKi, relative to bDMARDs for RA, is associated with an increased risk for herpes zoster but not other types of infections — is not a surprise, according to Floris A. van Gaalen, MD, PhD, a clinician and researcher in the Department of Rheumatology, Leiden University in the Netherlands.

“There are a number of risks with JAK inhibitors that have generated concern, but I think most clinicians are aware that they should be warning patients about herpes zoster,” said Dr. van Gaalen, who was not involved in the study. He believes the risk is sufficient to warrant a discussion with patients about taking the herpes zoster vaccine prior to treatment.

Relative Risk for Infection on JAKi Is Unclear

Although the greater risk for herpes zoster with JAKi vs bDMARDs is well established, the relative risk for other types of infections has been unclear, according to Mr. Aymon. One reason is that some, but not all, of the initial pivotal trials and safety studies associated JAKi with an increased risk for opportunistic infections, Mr. Aymon said.

The JAK-pot data, presented at the annual European Congress of Rheumatology, provide real-world data that shed light on this controversy, Mr. Aymon said.

Of the 20 national registries now providing data to JAK-pot, only 14 were included in this analysis. The study required data on infection rates from the time that JAKi became commercially available, which narrowed the data pool.

For this analysis, JAKi, which included tofacitinib (Xeljanz), baricitinib (Olumiant), upadacitinib (Rinvoq), and filgotinib (Jyseleca), were compared separately and together with two groups of bDMARDs. One consisted of the tumor necrosis factor inhibitors (TNFi), infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab. The other was composed of bDMARDs with other modes of action (OMA). This group included abatacept, rituximab, sarilumab, and tocilizumab.
 

More Than 50,000 Exposures Included in Analysis

From the pooled registry, data were gathered from 13,374 courses of JAKi, 25,049 courses of TNFi, and 16,482 courses of OMA. There were some differences between these groups, including a significantly lower median age for those in the JAKi pool (57.1 years vs 58.3 and 60.5 years for TNFi and OMA, respectively) and median disease duration (8.3 years vs 11.0 and 11.9 years, respectively).

A greater proportion of patients on TNFi were naive to therapy (44.6%), compared with either JAKi (20.2%) or OMA (16.1%). More patients in the TNFi pool (60.0%) were also on concomitant therapy than those in the JAKi pool (49.5%) or the OMA pool (51.9%).

Other characteristics such as disease activity, body mass index, and percentage of smokers were comparable.

When TNFi was used as the reference, there were no significant differences in the rate of all infections, the rate of all infections excluding herpes zoster, and all serious infections. In all three groups, the incidence rates were numerically but not significantly lower in patients on JAKi vs OMA. With the exception of serious infections, for which the adjusted incidence of JAKi was 0.99 relative to TNFi, both JAKi and OMA had numerically higher incidence rate ratios than TNFi.
 

Herpes Zoster Risk on JAKi Is > Twofold Higher

Because the CIs overlapped in all cases, none of the differences were significant. The exception was herpes zoster. The 1.07 incidence rate ratio for OMA was not significantly different than the TNFi reference, but the 2.27 rate ratio for JAKi far exceeded either of the other two comparators (95% CI, 1.17-3.02).

In a separate analysis of patients at least 55 years of age with at least one cardiovascular risk factor, the numerical differences between groups were narrower and thus did not reach statistical significance, even for herpes zoster. Although the herpes zoster rate ratio was 1.62 for JAKi vs 1.23 for OMA (TNFi as the reference was 1.0), the CI for JAKi (0.86-3.03) overlapped both.

Based on a Poisson regression analysis, this study took into account a wide variety of variables, including age, disease activity, comorbidities, and tobacco use, Mr. Aymon said. He noted that the analyses were performed on data from each registry as well as with the pooled data, and the data were reasonably consistent.

Initially, the investigators had planned to evaluate differences between therapy groups, if any, for COVID-19 infection, but differences in the availability and use of vaccinations among the countries where the registries were maintained made this analysis too complicated to conduct.

Mr. Aymon reported no potential conflicts of interest, but some coauthors reported financial relationships with manufacturers of both bDMARDs and JAKi. Dr. van Gaalen reported financial relationships with AbbVie, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, and UCB.

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.

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.