TBD Meeting (3388-19)

BIRMINGHAM, ENGLAND – Patients with rheumatoid arthritis (RA) who switch back to an original tumor necrosis factor inhibitor (TNFi) after using a biosimilar product often do so because of ineffectiveness, but this could be largely subjective, research suggests.

Data from the British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA), presented at the annual conference of the British Society for Rheumatology, have shown that the majority (81%) of 760 patients who switched from an etanercept originator (ETN-O) product (Enbrel) to an etanercept biosimilar (ETN-B) product (Benepali or Erelzi) remained on the latter at an average of 2 years’ follow-up.

However, of those who switched back to an ETN-O (8%, n = 58), ineffectiveness was the primary reason for doing so in more than half of patients (53%). Of patients who stopped ETN treatment altogether after the biosimilar switch (11%, n = 84), 29% stopped because of inefficacy. Other important reasons for switching back or stopping treatment were adverse events in 28% and 54% of cases, respectively. The switch back to an ETN-O happened within a median time of 4 months (range, 2–6 months).

Patients switching back to an ETN-O tended to be slightly younger than all patients who had switched to an ETN-B (median age 60 vs. 64 years). They were more likely to be female (79% vs. 75%). Median disease activity score in 28 joints (DAS28) at baseline were highest in those who discontinued ETN (3.9 vs. 3.2 for those who switched back and 3.0 for all who had switched to a biosimilar).

It is not known what is driving the purported ineffectiveness, said research assistant Rebecca Davies of the Arthritis Research UK Epidemiology Unit at the University of Manchester (England).

“It could be due to patient factors and a nocebo effect,” she suggested. This is where “negative patient expectations cause treatment to have a more negative effect.” For example, she added, “if a patient is settled on the originator drug and had to mandatorily switch to a biosimilar, it might be that they are more heightened to symptoms.”

Another explanation could be that consultants may be “overcautious” to continuing the biosimilar in patients who had responded well to the originator product, she hypothesized.

“Our next steps are to look at disease activity between 4 and 9 months post switch to determine” the cause of the described ineffectiveness.
 

Educate patients to reduce switchbacks?

Meanwhile data presented by a team of researchers from Imperial College Healthcare NHS Trust in London, headed by Maresa Carulli, MD, suggested that patient education may be an important factor in tackling why patients want to switch back to biosimilar treatment.

Over a 20-month period among 202 patients who were switched to an ETN-B after they had been established on an ETN-O, 27 (13.4%) switched back.

“The majority of patients who switched back to Enbrel reported subjective worsening of disease symptoms with Benepali,” Dr. Carulli and coauthors said in their poster. Indeed, 78% of patients who switched back after an average of just under 6 months reported that their symptoms had become worse on the biosimilar product.

Analysis of the RA patients (n = 16) who switched back demonstrated that DAS28 scores had increased by more than 1.2 points during the period of the switch, but this was “mainly due to increases in visual analog scores [VAS],” they said.

The average change in DAS28 was an increase of 1.32 points during the switch period, the researchers noted. The average changes in DAS28 components were: +5 and +0.44 points for the tender and swollen joint counts, +9.89 points for the erythrocyte sedimentation rate, and +25.56 points for VAS.

Although further data are need, the results “may suggest that a subjective component contributes toward intolerance” of the biosimilar product, the researchers said.

“Consideration of patient education during initiation of biosimilar treatment could be a significant factor in improving compliance with it.”

The BSR receives restricted income from multiple U.K. pharmaceutical companies, which is used to fund the BSRBR-RA. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or any decision to submit manuscripts for publication.

Ms. Davies and Dr. Carulli and team declared having no competing interests.

SOURCES: Davies R et al. Rheumatology. 2019;58(suppl 3), Abstract 022; and Dahanayake C et al. Rheumatology. 2019;58(suppl 3), Abstract 102

BIRMINGHAM, ENGLAND – Patients with rheumatoid arthritis (RA) who switch back to an original tumor necrosis factor inhibitor (TNFi) after using a biosimilar product often do so because of ineffectiveness, but this could be largely subjective, research suggests.

Data from the British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA), presented at the annual conference of the British Society for Rheumatology, have shown that the majority (81%) of 760 patients who switched from an etanercept originator (ETN-O) product (Enbrel) to an etanercept biosimilar (ETN-B) product (Benepali or Erelzi) remained on the latter at an average of 2 years’ follow-up.

However, of those who switched back to an ETN-O (8%, n = 58), ineffectiveness was the primary reason for doing so in more than half of patients (53%). Of patients who stopped ETN treatment altogether after the biosimilar switch (11%, n = 84), 29% stopped because of inefficacy. Other important reasons for switching back or stopping treatment were adverse events in 28% and 54% of cases, respectively. The switch back to an ETN-O happened within a median time of 4 months (range, 2–6 months).

Patients switching back to an ETN-O tended to be slightly younger than all patients who had switched to an ETN-B (median age 60 vs. 64 years). They were more likely to be female (79% vs. 75%). Median disease activity score in 28 joints (DAS28) at baseline were highest in those who discontinued ETN (3.9 vs. 3.2 for those who switched back and 3.0 for all who had switched to a biosimilar).

It is not known what is driving the purported ineffectiveness, said research assistant Rebecca Davies of the Arthritis Research UK Epidemiology Unit at the University of Manchester (England).

“It could be due to patient factors and a nocebo effect,” she suggested. This is where “negative patient expectations cause treatment to have a more negative effect.” For example, she added, “if a patient is settled on the originator drug and had to mandatorily switch to a biosimilar, it might be that they are more heightened to symptoms.”

Another explanation could be that consultants may be “overcautious” to continuing the biosimilar in patients who had responded well to the originator product, she hypothesized.

“Our next steps are to look at disease activity between 4 and 9 months post switch to determine” the cause of the described ineffectiveness.
 

Educate patients to reduce switchbacks?

Meanwhile data presented by a team of researchers from Imperial College Healthcare NHS Trust in London, headed by Maresa Carulli, MD, suggested that patient education may be an important factor in tackling why patients want to switch back to biosimilar treatment.

Over a 20-month period among 202 patients who were switched to an ETN-B after they had been established on an ETN-O, 27 (13.4%) switched back.

“The majority of patients who switched back to Enbrel reported subjective worsening of disease symptoms with Benepali,” Dr. Carulli and coauthors said in their poster. Indeed, 78% of patients who switched back after an average of just under 6 months reported that their symptoms had become worse on the biosimilar product.

Analysis of the RA patients (n = 16) who switched back demonstrated that DAS28 scores had increased by more than 1.2 points during the period of the switch, but this was “mainly due to increases in visual analog scores [VAS],” they said.

The average change in DAS28 was an increase of 1.32 points during the switch period, the researchers noted. The average changes in DAS28 components were: +5 and +0.44 points for the tender and swollen joint counts, +9.89 points for the erythrocyte sedimentation rate, and +25.56 points for VAS.

Although further data are need, the results “may suggest that a subjective component contributes toward intolerance” of the biosimilar product, the researchers said.

“Consideration of patient education during initiation of biosimilar treatment could be a significant factor in improving compliance with it.”

The BSR receives restricted income from multiple U.K. pharmaceutical companies, which is used to fund the BSRBR-RA. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or any decision to submit manuscripts for publication.

Ms. Davies and Dr. Carulli and team declared having no competing interests.

SOURCES: Davies R et al. Rheumatology. 2019;58(suppl 3), Abstract 022; and Dahanayake C et al. Rheumatology. 2019;58(suppl 3), Abstract 102

BIRMINGHAM, ENGLAND – Patients with rheumatoid arthritis (RA) who switch back to an original tumor necrosis factor inhibitor (TNFi) after using a biosimilar product often do so because of ineffectiveness, but this could be largely subjective, research suggests.

Data from the British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA), presented at the annual conference of the British Society for Rheumatology, have shown that the majority (81%) of 760 patients who switched from an etanercept originator (ETN-O) product (Enbrel) to an etanercept biosimilar (ETN-B) product (Benepali or Erelzi) remained on the latter at an average of 2 years’ follow-up.

However, of those who switched back to an ETN-O (8%, n = 58), ineffectiveness was the primary reason for doing so in more than half of patients (53%). Of patients who stopped ETN treatment altogether after the biosimilar switch (11%, n = 84), 29% stopped because of inefficacy. Other important reasons for switching back or stopping treatment were adverse events in 28% and 54% of cases, respectively. The switch back to an ETN-O happened within a median time of 4 months (range, 2–6 months).

Patients switching back to an ETN-O tended to be slightly younger than all patients who had switched to an ETN-B (median age 60 vs. 64 years). They were more likely to be female (79% vs. 75%). Median disease activity score in 28 joints (DAS28) at baseline were highest in those who discontinued ETN (3.9 vs. 3.2 for those who switched back and 3.0 for all who had switched to a biosimilar).

It is not known what is driving the purported ineffectiveness, said research assistant Rebecca Davies of the Arthritis Research UK Epidemiology Unit at the University of Manchester (England).

“It could be due to patient factors and a nocebo effect,” she suggested. This is where “negative patient expectations cause treatment to have a more negative effect.” For example, she added, “if a patient is settled on the originator drug and had to mandatorily switch to a biosimilar, it might be that they are more heightened to symptoms.”

Another explanation could be that consultants may be “overcautious” to continuing the biosimilar in patients who had responded well to the originator product, she hypothesized.

“Our next steps are to look at disease activity between 4 and 9 months post switch to determine” the cause of the described ineffectiveness.
 

Educate patients to reduce switchbacks?

Meanwhile data presented by a team of researchers from Imperial College Healthcare NHS Trust in London, headed by Maresa Carulli, MD, suggested that patient education may be an important factor in tackling why patients want to switch back to biosimilar treatment.

Over a 20-month period among 202 patients who were switched to an ETN-B after they had been established on an ETN-O, 27 (13.4%) switched back.

“The majority of patients who switched back to Enbrel reported subjective worsening of disease symptoms with Benepali,” Dr. Carulli and coauthors said in their poster. Indeed, 78% of patients who switched back after an average of just under 6 months reported that their symptoms had become worse on the biosimilar product.

Analysis of the RA patients (n = 16) who switched back demonstrated that DAS28 scores had increased by more than 1.2 points during the period of the switch, but this was “mainly due to increases in visual analog scores [VAS],” they said.

The average change in DAS28 was an increase of 1.32 points during the switch period, the researchers noted. The average changes in DAS28 components were: +5 and +0.44 points for the tender and swollen joint counts, +9.89 points for the erythrocyte sedimentation rate, and +25.56 points for VAS.

Although further data are need, the results “may suggest that a subjective component contributes toward intolerance” of the biosimilar product, the researchers said.

“Consideration of patient education during initiation of biosimilar treatment could be a significant factor in improving compliance with it.”

The BSR receives restricted income from multiple U.K. pharmaceutical companies, which is used to fund the BSRBR-RA. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or any decision to submit manuscripts for publication.

Ms. Davies and Dr. Carulli and team declared having no competing interests.

SOURCES: Davies R et al. Rheumatology. 2019;58(suppl 3), Abstract 022; and Dahanayake C et al. Rheumatology. 2019;58(suppl 3), Abstract 102

BIRMINGHAM, ENGLAND – Proinflammatory diets are associated with increased C-reactive protein (CRP) and subsequent rheumatoid arthritis (RA), according to combined data from the European Prospective Investigation of Cancer and Nutrition (EPIC) and Norfolk Arthritis Register (NOAR).

Sara Freeman/MDedge News

“There has always been a debate around this topic,” Max Yates, MBBS, PhD, said at the annual conference of the British Society for Rheumatology. “A quick online search will reveal a plethora of texts claiming to give definitive or the best advice for arthritis” and diet, he said, often from “questionable experts.”

“I think we’re all interested in diet,” observed Dr. Yates, of the University of East Anglia in Norwich (England), and “although the association between diet and arthritis is open to debate, previous studies have shown an association with those who have a lower intake of vitamin C and fiber.” The problem is one of credibility, he noted, so this was something that the NOAR investigators decided to look into with data from the Dietary Inflammatory Index (DII) collected from the EPIC cohort.

The DII is a literature-based, population-derived tool that has been used to determine the inflammatory potential of diet, Dr. Yates explained. Data show that inflammatory diets are is associated with increased levels of inflammatory markers including C-reactive protein (CRP) and interleukin (IL)-6. These diets include items such as trans and saturated fats, and fats from animal protein versus more anti-inflammatory items such as black tea, thyme, turmeric, and saffron.

“We are fortunate that NOAR is in the same geographic location as EPIC,” Dr. Yates said, and the two cohorts have been running alongside each other since the early 1990s. While NOAR has been collecting data on incident inflammatory polyarthritis since 1989, EPIC has been “intensively” collecting information on dietary and lifestyle factors and blood samples from its participants since 1993.

EPIC investigators have been “trailblazers” in recording of dietary data, Dr. Yates said. First using paper-based questionnaires and now smartphone apps that allow people to upload photos of what they are eating. Data are linked to both primary care practice and hospital records.

For the present study, data on 159 patients who participated in both NOAR and EPIC were used. Participants had RA according to the 2010 American College of Rheumatology criteria and had an average disease onset of 7 years after enrollment into NOAR and EPIC.

“Quite pleasingly, the dietary inflammatory index scores were associated with high-sensitivity CRP taken at baseline enrollment in 1993 to 1997, further validating the index again within another population,” Dr. Yates said.

Results showed that there was a significant association between the baseline DII score and subsequent development of RA, with an odds ratio of 1.90 comparing individuals with the highest and lowest DII scores (P less than .01).

When cases were matched by age, sex, and body mass index, however, there was only a trend for an association between inflammatory diets and RA onset. “We hope to identify more patients within EPIC to strengthen this association,” Dr. Yates said.

The results are consistent with data from the Nurses’ Health Study, Dr. Yates noted, adding that future research is needed to address whether dietary modification can demonstrate causality.

“Diet is one of the modifiable risk factors that we can use to tackle RA, and I think it’s about time we as a community take over this area and gave definitive advice.”

Dr. Yates presented the work on behalf of PhD student Ellie Sayer. Neither Dr. Yates nor Ms. Sayer had any conflicts of interests to disclose.

SOURCE: Sayer E et al. Rheumatology. 2019;58(suppl 3), Abstract 014.

BIRMINGHAM, ENGLAND – Proinflammatory diets are associated with increased C-reactive protein (CRP) and subsequent rheumatoid arthritis (RA), according to combined data from the European Prospective Investigation of Cancer and Nutrition (EPIC) and Norfolk Arthritis Register (NOAR).

Sara Freeman/MDedge News

“There has always been a debate around this topic,” Max Yates, MBBS, PhD, said at the annual conference of the British Society for Rheumatology. “A quick online search will reveal a plethora of texts claiming to give definitive or the best advice for arthritis” and diet, he said, often from “questionable experts.”

“I think we’re all interested in diet,” observed Dr. Yates, of the University of East Anglia in Norwich (England), and “although the association between diet and arthritis is open to debate, previous studies have shown an association with those who have a lower intake of vitamin C and fiber.” The problem is one of credibility, he noted, so this was something that the NOAR investigators decided to look into with data from the Dietary Inflammatory Index (DII) collected from the EPIC cohort.

The DII is a literature-based, population-derived tool that has been used to determine the inflammatory potential of diet, Dr. Yates explained. Data show that inflammatory diets are is associated with increased levels of inflammatory markers including C-reactive protein (CRP) and interleukin (IL)-6. These diets include items such as trans and saturated fats, and fats from animal protein versus more anti-inflammatory items such as black tea, thyme, turmeric, and saffron.

“We are fortunate that NOAR is in the same geographic location as EPIC,” Dr. Yates said, and the two cohorts have been running alongside each other since the early 1990s. While NOAR has been collecting data on incident inflammatory polyarthritis since 1989, EPIC has been “intensively” collecting information on dietary and lifestyle factors and blood samples from its participants since 1993.

EPIC investigators have been “trailblazers” in recording of dietary data, Dr. Yates said. First using paper-based questionnaires and now smartphone apps that allow people to upload photos of what they are eating. Data are linked to both primary care practice and hospital records.

For the present study, data on 159 patients who participated in both NOAR and EPIC were used. Participants had RA according to the 2010 American College of Rheumatology criteria and had an average disease onset of 7 years after enrollment into NOAR and EPIC.

“Quite pleasingly, the dietary inflammatory index scores were associated with high-sensitivity CRP taken at baseline enrollment in 1993 to 1997, further validating the index again within another population,” Dr. Yates said.

Results showed that there was a significant association between the baseline DII score and subsequent development of RA, with an odds ratio of 1.90 comparing individuals with the highest and lowest DII scores (P less than .01).

When cases were matched by age, sex, and body mass index, however, there was only a trend for an association between inflammatory diets and RA onset. “We hope to identify more patients within EPIC to strengthen this association,” Dr. Yates said.

The results are consistent with data from the Nurses’ Health Study, Dr. Yates noted, adding that future research is needed to address whether dietary modification can demonstrate causality.

“Diet is one of the modifiable risk factors that we can use to tackle RA, and I think it’s about time we as a community take over this area and gave definitive advice.”

Dr. Yates presented the work on behalf of PhD student Ellie Sayer. Neither Dr. Yates nor Ms. Sayer had any conflicts of interests to disclose.

SOURCE: Sayer E et al. Rheumatology. 2019;58(suppl 3), Abstract 014.

BIRMINGHAM, ENGLAND – Proinflammatory diets are associated with increased C-reactive protein (CRP) and subsequent rheumatoid arthritis (RA), according to combined data from the European Prospective Investigation of Cancer and Nutrition (EPIC) and Norfolk Arthritis Register (NOAR).

Sara Freeman/MDedge News

“There has always been a debate around this topic,” Max Yates, MBBS, PhD, said at the annual conference of the British Society for Rheumatology. “A quick online search will reveal a plethora of texts claiming to give definitive or the best advice for arthritis” and diet, he said, often from “questionable experts.”

“I think we’re all interested in diet,” observed Dr. Yates, of the University of East Anglia in Norwich (England), and “although the association between diet and arthritis is open to debate, previous studies have shown an association with those who have a lower intake of vitamin C and fiber.” The problem is one of credibility, he noted, so this was something that the NOAR investigators decided to look into with data from the Dietary Inflammatory Index (DII) collected from the EPIC cohort.

The DII is a literature-based, population-derived tool that has been used to determine the inflammatory potential of diet, Dr. Yates explained. Data show that inflammatory diets are is associated with increased levels of inflammatory markers including C-reactive protein (CRP) and interleukin (IL)-6. These diets include items such as trans and saturated fats, and fats from animal protein versus more anti-inflammatory items such as black tea, thyme, turmeric, and saffron.

“We are fortunate that NOAR is in the same geographic location as EPIC,” Dr. Yates said, and the two cohorts have been running alongside each other since the early 1990s. While NOAR has been collecting data on incident inflammatory polyarthritis since 1989, EPIC has been “intensively” collecting information on dietary and lifestyle factors and blood samples from its participants since 1993.

EPIC investigators have been “trailblazers” in recording of dietary data, Dr. Yates said. First using paper-based questionnaires and now smartphone apps that allow people to upload photos of what they are eating. Data are linked to both primary care practice and hospital records.

For the present study, data on 159 patients who participated in both NOAR and EPIC were used. Participants had RA according to the 2010 American College of Rheumatology criteria and had an average disease onset of 7 years after enrollment into NOAR and EPIC.

“Quite pleasingly, the dietary inflammatory index scores were associated with high-sensitivity CRP taken at baseline enrollment in 1993 to 1997, further validating the index again within another population,” Dr. Yates said.

Results showed that there was a significant association between the baseline DII score and subsequent development of RA, with an odds ratio of 1.90 comparing individuals with the highest and lowest DII scores (P less than .01).

When cases were matched by age, sex, and body mass index, however, there was only a trend for an association between inflammatory diets and RA onset. “We hope to identify more patients within EPIC to strengthen this association,” Dr. Yates said.

The results are consistent with data from the Nurses’ Health Study, Dr. Yates noted, adding that future research is needed to address whether dietary modification can demonstrate causality.

“Diet is one of the modifiable risk factors that we can use to tackle RA, and I think it’s about time we as a community take over this area and gave definitive advice.”

Dr. Yates presented the work on behalf of PhD student Ellie Sayer. Neither Dr. Yates nor Ms. Sayer had any conflicts of interests to disclose.

SOURCE: Sayer E et al. Rheumatology. 2019;58(suppl 3), Abstract 014.

BIRMINGHAM, ENGLAND – Almost two-thirds of patients with axial spondyloarthritis (axSpA) have more than one medical condition, and these may cluster together, the results of a single-center, cross-sectional study have shown.

Of 419 patients, 61% had multiple conditions, with a median of at least one other condition in addition to axSpA, but some patients had as many as five. The most common other conditions in patients with axSpA were hypertension (19% of patients), depression (16%), and dyspepsia (11%).

In all, 15 clusters of conditions were found, each dominated by one or two conditions in addition to axSpA. The three largest clusters were hypertension and cardiovascular disease (n = 88), anxiety and depression (n = 50), and dyspepsia (n = 31). In the cohort, 69% of the patients were male; the mean age was 45 years.

“Multimorbidity and comorbidity both essentially mean the same thing but from different perspectives,” Sizheng Steven Zhao, MD, said at the annual conference of the British Society for Rheumatology.

“Many of us will be familiar with comorbidity and this is a concept that has one index disease at the center and we consider all other conditions to be coexisting. This is a model you typically see in hospital settings, so you go to see your rheumatologist for your axSpA and your cardiologist for your cardiovascular disease,” he explained.

“From a patient’s perspective, that’s probably a little less helpful to go from specialist to specialist, each only interested in one condition so, quite rightly, there’s been a push towards providing more holistic care with the patient at the center, and this is really encapsulated by the concept of multimorbidity, which is just defined as the coexistence of any two conditions.” The multimorbidity model is particularly suited to a primary care setting rather than a hospital setting, he added.

“Whatever you want to call it, it’s becoming more of a problem,” Dr. Zhao said. There is increasing multimorbidity as people age, and it’s a common problem in those with rheumatic diseases because of shared risk factors, the consequences of systemic inflammation, and how patients are treated.

Prior studies of multimorbidity in axSpA have either been of individual comorbid diseases or counts. Dr. Zhao, a clinical research fellow at Aintree University Hospital in Liverpool, England, and his associates looked at how coexisting conditions might cluster together to provide insight into how these might be better managed collectively in patients with axSpA.


The investigators used an adapted form of the Radner index for determining multimorbidity in patients consecutively seen at the Aintree University Hospital’s rheumatology clinic between 2010 and 2017. The Radner index was adapted to consider 40 chronic conditions, including fibromyalgia and osteoporosis but excluding rheumatic diseases and their extra-articular manifestations.

Dr. Zhao and his colleagues used regression models adjusted for age, gender, symptom duration, smoking status, body mass index, social deprivation, and NSAID use to see what, if any, effect having one of these clusters of multimorbid conditions might have on quality of life, general health, disease activity, and functional impairment measures. Patients with certain clusters of conditions had worse scores, particularly those with coexisting depression and/or anxiety and those with fibromyalgia, irritable bowel syndrome, or both in addition to axSpA.

“These are important conditions to be aware of in the management of axSpA patients,” Dr. Zhao said.

These data are consistent with what has already been published, with between 50% and 60% of patients having other conditions, particularly depression, said consultant rheumatologist Helena Marzo-Ortega, MD, of Leeds Teaching Hospitals NHS Trust, who chaired the session. “These are really important numbers for us to remember in the clinic,” she said.

None of the investigators reported having relevant disclosures.

SOURCE: Zhao S et al., Rheumatology 2019;58(suppl 3), Abstract 035.

BIRMINGHAM, ENGLAND – Almost two-thirds of patients with axial spondyloarthritis (axSpA) have more than one medical condition, and these may cluster together, the results of a single-center, cross-sectional study have shown.

Of 419 patients, 61% had multiple conditions, with a median of at least one other condition in addition to axSpA, but some patients had as many as five. The most common other conditions in patients with axSpA were hypertension (19% of patients), depression (16%), and dyspepsia (11%).

In all, 15 clusters of conditions were found, each dominated by one or two conditions in addition to axSpA. The three largest clusters were hypertension and cardiovascular disease (n = 88), anxiety and depression (n = 50), and dyspepsia (n = 31). In the cohort, 69% of the patients were male; the mean age was 45 years.

“Multimorbidity and comorbidity both essentially mean the same thing but from different perspectives,” Sizheng Steven Zhao, MD, said at the annual conference of the British Society for Rheumatology.

“Many of us will be familiar with comorbidity and this is a concept that has one index disease at the center and we consider all other conditions to be coexisting. This is a model you typically see in hospital settings, so you go to see your rheumatologist for your axSpA and your cardiologist for your cardiovascular disease,” he explained.

“From a patient’s perspective, that’s probably a little less helpful to go from specialist to specialist, each only interested in one condition so, quite rightly, there’s been a push towards providing more holistic care with the patient at the center, and this is really encapsulated by the concept of multimorbidity, which is just defined as the coexistence of any two conditions.” The multimorbidity model is particularly suited to a primary care setting rather than a hospital setting, he added.

“Whatever you want to call it, it’s becoming more of a problem,” Dr. Zhao said. There is increasing multimorbidity as people age, and it’s a common problem in those with rheumatic diseases because of shared risk factors, the consequences of systemic inflammation, and how patients are treated.

Prior studies of multimorbidity in axSpA have either been of individual comorbid diseases or counts. Dr. Zhao, a clinical research fellow at Aintree University Hospital in Liverpool, England, and his associates looked at how coexisting conditions might cluster together to provide insight into how these might be better managed collectively in patients with axSpA.


The investigators used an adapted form of the Radner index for determining multimorbidity in patients consecutively seen at the Aintree University Hospital’s rheumatology clinic between 2010 and 2017. The Radner index was adapted to consider 40 chronic conditions, including fibromyalgia and osteoporosis but excluding rheumatic diseases and their extra-articular manifestations.

Dr. Zhao and his colleagues used regression models adjusted for age, gender, symptom duration, smoking status, body mass index, social deprivation, and NSAID use to see what, if any, effect having one of these clusters of multimorbid conditions might have on quality of life, general health, disease activity, and functional impairment measures. Patients with certain clusters of conditions had worse scores, particularly those with coexisting depression and/or anxiety and those with fibromyalgia, irritable bowel syndrome, or both in addition to axSpA.

“These are important conditions to be aware of in the management of axSpA patients,” Dr. Zhao said.

These data are consistent with what has already been published, with between 50% and 60% of patients having other conditions, particularly depression, said consultant rheumatologist Helena Marzo-Ortega, MD, of Leeds Teaching Hospitals NHS Trust, who chaired the session. “These are really important numbers for us to remember in the clinic,” she said.

None of the investigators reported having relevant disclosures.

SOURCE: Zhao S et al., Rheumatology 2019;58(suppl 3), Abstract 035.

BIRMINGHAM, ENGLAND – Almost two-thirds of patients with axial spondyloarthritis (axSpA) have more than one medical condition, and these may cluster together, the results of a single-center, cross-sectional study have shown.

Of 419 patients, 61% had multiple conditions, with a median of at least one other condition in addition to axSpA, but some patients had as many as five. The most common other conditions in patients with axSpA were hypertension (19% of patients), depression (16%), and dyspepsia (11%).

In all, 15 clusters of conditions were found, each dominated by one or two conditions in addition to axSpA. The three largest clusters were hypertension and cardiovascular disease (n = 88), anxiety and depression (n = 50), and dyspepsia (n = 31). In the cohort, 69% of the patients were male; the mean age was 45 years.

“Multimorbidity and comorbidity both essentially mean the same thing but from different perspectives,” Sizheng Steven Zhao, MD, said at the annual conference of the British Society for Rheumatology.

“Many of us will be familiar with comorbidity and this is a concept that has one index disease at the center and we consider all other conditions to be coexisting. This is a model you typically see in hospital settings, so you go to see your rheumatologist for your axSpA and your cardiologist for your cardiovascular disease,” he explained.

“From a patient’s perspective, that’s probably a little less helpful to go from specialist to specialist, each only interested in one condition so, quite rightly, there’s been a push towards providing more holistic care with the patient at the center, and this is really encapsulated by the concept of multimorbidity, which is just defined as the coexistence of any two conditions.” The multimorbidity model is particularly suited to a primary care setting rather than a hospital setting, he added.

“Whatever you want to call it, it’s becoming more of a problem,” Dr. Zhao said. There is increasing multimorbidity as people age, and it’s a common problem in those with rheumatic diseases because of shared risk factors, the consequences of systemic inflammation, and how patients are treated.

Prior studies of multimorbidity in axSpA have either been of individual comorbid diseases or counts. Dr. Zhao, a clinical research fellow at Aintree University Hospital in Liverpool, England, and his associates looked at how coexisting conditions might cluster together to provide insight into how these might be better managed collectively in patients with axSpA.


The investigators used an adapted form of the Radner index for determining multimorbidity in patients consecutively seen at the Aintree University Hospital’s rheumatology clinic between 2010 and 2017. The Radner index was adapted to consider 40 chronic conditions, including fibromyalgia and osteoporosis but excluding rheumatic diseases and their extra-articular manifestations.

Dr. Zhao and his colleagues used regression models adjusted for age, gender, symptom duration, smoking status, body mass index, social deprivation, and NSAID use to see what, if any, effect having one of these clusters of multimorbid conditions might have on quality of life, general health, disease activity, and functional impairment measures. Patients with certain clusters of conditions had worse scores, particularly those with coexisting depression and/or anxiety and those with fibromyalgia, irritable bowel syndrome, or both in addition to axSpA.

“These are important conditions to be aware of in the management of axSpA patients,” Dr. Zhao said.

These data are consistent with what has already been published, with between 50% and 60% of patients having other conditions, particularly depression, said consultant rheumatologist Helena Marzo-Ortega, MD, of Leeds Teaching Hospitals NHS Trust, who chaired the session. “These are really important numbers for us to remember in the clinic,” she said.

None of the investigators reported having relevant disclosures.

SOURCE: Zhao S et al., Rheumatology 2019;58(suppl 3), Abstract 035.

BIRMINGHAM, ENGLAND – Being diagnosed with rheumatoid arthritis at age 75 years or older made it less likely that patients would receive intensive therapy than their younger counterparts, but that did not mean that they were treated any less favorably overall, according to findings derived from the Early RA Network cohort.

“The claim that the elderly are treated less aggressively isn’t completely true throughout the whole treat-to-target strategy,” said Simone Howard of King’s College London at the British Society for Rheumatology annual conference. While older patients were less likely to receive intensive treatment up to 2 years after their diagnosis, there was a shorter delay between the onset of symptoms and the first outpatient visit to a rheumatology clinic.

When compared against patients who were younger than 65 years, those aged 65-74 years and 75 years and older were 11% (P = .02) and 15% (P = .02) more likely to have their first outpatient visit within 10 months.

Furthermore, no significant differences were seen between any age groups in the time to first initiation of a conventional synthetic disease-modifying antirheumatic drug (csDMARD), which averaged nearly 3 months after symptoms appeared.

Ms. Howard, who has previously worked at the European Medicines Agency, noted that, during her time at the EMA, “there was a real push to incorporate the elderly into the regulatory framework more. In parallel, there were also reports of the elderly being treated less aggressively. So the question was, where was that coming from?”

Similar therapeutic approaches are advocated for older and younger RA patients, and to look for any disparities, Ms. Howard and associates turned to the Early RA Network (ERAN) to “investigate potential treatment bias against the elderly.”

ERAN is a hospital-based inception cohort of 1,236 patients with early RA who were recruited across 23 centers in the United Kingdom and Ireland between 2002 and 2014.

Of 1,131 patients used in the analyses, 9.7% (n = 110) were 75 years or older, 21.5% (n = 243) were aged 65-74 years, and 68.8% (n = 778) were 65 years or younger. The majority (67.7%) of patients were female.

Patients aged 75 years and older were more likely to present with comorbidities than the youngest group, and they had higher health assessment questionnaire scores at baseline. However, they were no more likely to have high disease activity at the first visit, which was defined as a disease activity score in 28 joints of more than 5, and the older patients were 27% less likely to be seropositive (P = .004).

“It’s when we come to pharmacological aspects of care that we are seeing treatment biases,” Ms. Howard noted. Patients over 75 years were significantly more likely than the youngest age group to be treated with glucocorticoids or csDMARD monotherapy at 1 year, and 23% more likely to be on less aggressive therapy (P equal to or less than .0001). Aggressive therapy was defined as the use of a combination of csDMARDs or the use of biologic drugs.

At 2 years, the oldest patients were 46% more likely than those under 65 years to be on less-intensive therapies (P equal to or less than .0001), with those aged 65-74 years 19% more likely to be on glucocorticoid or csDMARD therapy (P = .005).

Factors such as patient choice and tolerance were not considered in the analyses and could be important, Ms. Howard conceded in response to a question after her presentation.

Another point raised was that perhaps the prescribing of aggressive therapy would rationally be different in someone diagnosed with RA at age 85 versus 65 because the duration of time that would be likely to be lived with accumulating joint damage would be shorter at the older age and that would be balanced against the other effects of the therapy. So, there may be important reasons in shared decision making that influenced the treatment choices other than the age of patients.

Ms. Howard agreed, noting that this demonstrated the need to be careful around the language used for defining what constituted aggressive or intensive therapy.

She and her coauthors reported no conflicts of interest.

SOURCE: Howard S et al. Rheumatology. 2019;58(suppl 3), Abstract 011.

BIRMINGHAM, ENGLAND – Being diagnosed with rheumatoid arthritis at age 75 years or older made it less likely that patients would receive intensive therapy than their younger counterparts, but that did not mean that they were treated any less favorably overall, according to findings derived from the Early RA Network cohort.

“The claim that the elderly are treated less aggressively isn’t completely true throughout the whole treat-to-target strategy,” said Simone Howard of King’s College London at the British Society for Rheumatology annual conference. While older patients were less likely to receive intensive treatment up to 2 years after their diagnosis, there was a shorter delay between the onset of symptoms and the first outpatient visit to a rheumatology clinic.

When compared against patients who were younger than 65 years, those aged 65-74 years and 75 years and older were 11% (P = .02) and 15% (P = .02) more likely to have their first outpatient visit within 10 months.

Furthermore, no significant differences were seen between any age groups in the time to first initiation of a conventional synthetic disease-modifying antirheumatic drug (csDMARD), which averaged nearly 3 months after symptoms appeared.

Ms. Howard, who has previously worked at the European Medicines Agency, noted that, during her time at the EMA, “there was a real push to incorporate the elderly into the regulatory framework more. In parallel, there were also reports of the elderly being treated less aggressively. So the question was, where was that coming from?”

Similar therapeutic approaches are advocated for older and younger RA patients, and to look for any disparities, Ms. Howard and associates turned to the Early RA Network (ERAN) to “investigate potential treatment bias against the elderly.”

ERAN is a hospital-based inception cohort of 1,236 patients with early RA who were recruited across 23 centers in the United Kingdom and Ireland between 2002 and 2014.

Of 1,131 patients used in the analyses, 9.7% (n = 110) were 75 years or older, 21.5% (n = 243) were aged 65-74 years, and 68.8% (n = 778) were 65 years or younger. The majority (67.7%) of patients were female.

Patients aged 75 years and older were more likely to present with comorbidities than the youngest group, and they had higher health assessment questionnaire scores at baseline. However, they were no more likely to have high disease activity at the first visit, which was defined as a disease activity score in 28 joints of more than 5, and the older patients were 27% less likely to be seropositive (P = .004).

“It’s when we come to pharmacological aspects of care that we are seeing treatment biases,” Ms. Howard noted. Patients over 75 years were significantly more likely than the youngest age group to be treated with glucocorticoids or csDMARD monotherapy at 1 year, and 23% more likely to be on less aggressive therapy (P equal to or less than .0001). Aggressive therapy was defined as the use of a combination of csDMARDs or the use of biologic drugs.

At 2 years, the oldest patients were 46% more likely than those under 65 years to be on less-intensive therapies (P equal to or less than .0001), with those aged 65-74 years 19% more likely to be on glucocorticoid or csDMARD therapy (P = .005).

Factors such as patient choice and tolerance were not considered in the analyses and could be important, Ms. Howard conceded in response to a question after her presentation.

Another point raised was that perhaps the prescribing of aggressive therapy would rationally be different in someone diagnosed with RA at age 85 versus 65 because the duration of time that would be likely to be lived with accumulating joint damage would be shorter at the older age and that would be balanced against the other effects of the therapy. So, there may be important reasons in shared decision making that influenced the treatment choices other than the age of patients.

Ms. Howard agreed, noting that this demonstrated the need to be careful around the language used for defining what constituted aggressive or intensive therapy.

She and her coauthors reported no conflicts of interest.

SOURCE: Howard S et al. Rheumatology. 2019;58(suppl 3), Abstract 011.

BIRMINGHAM, ENGLAND – Being diagnosed with rheumatoid arthritis at age 75 years or older made it less likely that patients would receive intensive therapy than their younger counterparts, but that did not mean that they were treated any less favorably overall, according to findings derived from the Early RA Network cohort.

“The claim that the elderly are treated less aggressively isn’t completely true throughout the whole treat-to-target strategy,” said Simone Howard of King’s College London at the British Society for Rheumatology annual conference. While older patients were less likely to receive intensive treatment up to 2 years after their diagnosis, there was a shorter delay between the onset of symptoms and the first outpatient visit to a rheumatology clinic.

When compared against patients who were younger than 65 years, those aged 65-74 years and 75 years and older were 11% (P = .02) and 15% (P = .02) more likely to have their first outpatient visit within 10 months.

Furthermore, no significant differences were seen between any age groups in the time to first initiation of a conventional synthetic disease-modifying antirheumatic drug (csDMARD), which averaged nearly 3 months after symptoms appeared.

Ms. Howard, who has previously worked at the European Medicines Agency, noted that, during her time at the EMA, “there was a real push to incorporate the elderly into the regulatory framework more. In parallel, there were also reports of the elderly being treated less aggressively. So the question was, where was that coming from?”

Similar therapeutic approaches are advocated for older and younger RA patients, and to look for any disparities, Ms. Howard and associates turned to the Early RA Network (ERAN) to “investigate potential treatment bias against the elderly.”

ERAN is a hospital-based inception cohort of 1,236 patients with early RA who were recruited across 23 centers in the United Kingdom and Ireland between 2002 and 2014.

Of 1,131 patients used in the analyses, 9.7% (n = 110) were 75 years or older, 21.5% (n = 243) were aged 65-74 years, and 68.8% (n = 778) were 65 years or younger. The majority (67.7%) of patients were female.

Patients aged 75 years and older were more likely to present with comorbidities than the youngest group, and they had higher health assessment questionnaire scores at baseline. However, they were no more likely to have high disease activity at the first visit, which was defined as a disease activity score in 28 joints of more than 5, and the older patients were 27% less likely to be seropositive (P = .004).

“It’s when we come to pharmacological aspects of care that we are seeing treatment biases,” Ms. Howard noted. Patients over 75 years were significantly more likely than the youngest age group to be treated with glucocorticoids or csDMARD monotherapy at 1 year, and 23% more likely to be on less aggressive therapy (P equal to or less than .0001). Aggressive therapy was defined as the use of a combination of csDMARDs or the use of biologic drugs.

At 2 years, the oldest patients were 46% more likely than those under 65 years to be on less-intensive therapies (P equal to or less than .0001), with those aged 65-74 years 19% more likely to be on glucocorticoid or csDMARD therapy (P = .005).

Factors such as patient choice and tolerance were not considered in the analyses and could be important, Ms. Howard conceded in response to a question after her presentation.

Another point raised was that perhaps the prescribing of aggressive therapy would rationally be different in someone diagnosed with RA at age 85 versus 65 because the duration of time that would be likely to be lived with accumulating joint damage would be shorter at the older age and that would be balanced against the other effects of the therapy. So, there may be important reasons in shared decision making that influenced the treatment choices other than the age of patients.

Ms. Howard agreed, noting that this demonstrated the need to be careful around the language used for defining what constituted aggressive or intensive therapy.

She and her coauthors reported no conflicts of interest.

SOURCE: Howard S et al. Rheumatology. 2019;58(suppl 3), Abstract 011.

BIRMINGHAM, ENGLAND – Data from two early RA inception cohorts provide reassurance that methotrexate does not cause interstitial lung disease and suggest that treatment with methotrexate might even be protective.

Sara Freeman/MDedge News

In the Early RA Study (ERAS) and Early RA Network (ERAN), which together include 2,701 patients with RA, 101 (3.7%) had interstitial lung disease (ILD). There were 92 patients with RA-ILD who had information available on exposure to any conventional synthetic disease-modifying antirheumatic drug (csDMARD); of these, 39 (2.5%) had been exposed to methotrexate (n = 1,578) and 53 (4.8%) to other csDMARDs (n = 1,114).

Multivariate analysis showed that methotrexate exposure was associated with a reduced risk of developing ILD, with an odds ratio of 0.48 (P = .004). In a separate analysis that excluded 25 patients who had ILD before they received any csDMARD therapy (n = 67), there was no association between methotrexate use and ILD (OR, 0.85; P = .578). In fact, there was a nonsignificant trend for a delayed onset of ILD in patients who had been treated with methotrexate (OR, 0.54; P = .072).

Methotrexate use is associated with an acute hypersensitivity pneumonitis in patients with RA, explained Patrick Kiely, MBBS, PhD, of St. George’s University Hospitals NHS Foundation Trust in London at the British Society for Rheumatology annual conference. “This is well recognized, it’s very rare [0.43%-1.00%], it’s easy to spot, and usually goes away if you stop methotrexate,” said Dr. Kiely, adding that “it’s not benign, and severe cases can be life threatening.”

Because of the association between methotrexate and pneumonitis, there has been concern that methotrexate may exacerbate or even cause ILD in RA but there are sparse data available to confirm this. The bottom line is that you should not start someone on methotrexate if you think their existing lung capacity is not up to treatment with methotrexate, Dr. Kiely said.

ILD is not always symptomatic in RA, but when it is, it is associated with very poor survival. The lung disease can be present before joint symptoms, Dr. Kiely said. Although less than 10% of cases may be symptomatic, this “is a big deal, because it has a high mortality, with death within 5 years. It’s the second-commonest cause of excess mortality in RA after cardiovascular disease.”

To look at the association between incident RA-ILD and the use of methotrexate, Dr. Kiely and associates analyzed data from ERAS (1986-2001) and ERAN (2002-2013), that together have more than 25 years of follow-up data on patients who were recruited at the first sign of RA symptoms. Patients within these cohorts have been treated according to best practice, and a range of outcomes – including RA-ILD – have been assessed at annual intervals.

In the patients who developed ILD after any csDMARD exposure, older age at RA onset (OR, 1.04; P less than .001) and having ever smoked (OR, 1.91; P = .016) were associated with the development of the lung disease. Incident ILD was also associated with being positive for rheumatoid factor (OR, 2.02; P = .029) at baseline. Being male was also associated with a higher risk for developing ILD, Dr. Kiely reported, as was a longer duration of time between the onset of first RA symptoms and the first secondary care visit. Conversely, the presence of nonrespiratory, major comorbidities at baseline appeared to be protective (OR, 0.62; P = .027).

“We found no association between methotrexate treatment and incident RA-ILD and a possibility that it may be protective,” Dr. Kiely concluded, noting that these data were now published in BMJ Open (2019;9:e028466. doi: 10.1136/bmjopen-2018-028466).

Following Dr. Kiely’s presentation, an audience member asked if the protective effect seen with methotrexate could have been caused by better disease control overall.

Dr. Kiely answered that, up until 2001, the time when ERAS was ongoing, standard practice in the United Kingdom was to use sulfasalazine, but then methotrexate started to be used in higher and higher doses, as seen in ERAN.

The interesting thing is that in ERAN more methotrexate was used in higher doses, but less RA-ILD was seen, Dr. Kiely observed. The overall prevalence of RA-ILD in the later early RA cohort was 3.2% and the median dose of methotrexate used was 20 mg. In ERAS, the prevalence was 4.2% and the median dose of methotrexate used was 10 mg.

There was a suggestion that disease control was slightly better in ERAN than ERAS, but that wasn’t statistically significant, Dr. Kiely said.

So, should a patient with RA and ILD be given methotrexate? There’s no reason not to, Dr. Kiely suggested, based on the evidence shown. Part of the challenge will now be convincing chest physician colleagues that methotrexate is not problematic in terms of causing ILD.

These findings are completely on board with the ILD group’s findings that methotrexate doesn’t cause pulmonary fibrosis in patients with RA, commented Julie Dawson, MD, of St. Helens and Knowsley Teaching Hospitals NHS Trust, St. Helens, England. Her own research, which includes a 10-year follow-up of patients with inflammatory arthritis, has shown that methotrexate does not appear to increase the risk of pulmonary fibrosis.

The study had no specific outside funding. Dr. Kiely reported having no conflicts of interest.

SOURCE: Kiely P et al. Rheumatology. 2019;58(suppl 3), Abstract 009.

BIRMINGHAM, ENGLAND – Data from two early RA inception cohorts provide reassurance that methotrexate does not cause interstitial lung disease and suggest that treatment with methotrexate might even be protective.

Sara Freeman/MDedge News

In the Early RA Study (ERAS) and Early RA Network (ERAN), which together include 2,701 patients with RA, 101 (3.7%) had interstitial lung disease (ILD). There were 92 patients with RA-ILD who had information available on exposure to any conventional synthetic disease-modifying antirheumatic drug (csDMARD); of these, 39 (2.5%) had been exposed to methotrexate (n = 1,578) and 53 (4.8%) to other csDMARDs (n = 1,114).

Multivariate analysis showed that methotrexate exposure was associated with a reduced risk of developing ILD, with an odds ratio of 0.48 (P = .004). In a separate analysis that excluded 25 patients who had ILD before they received any csDMARD therapy (n = 67), there was no association between methotrexate use and ILD (OR, 0.85; P = .578). In fact, there was a nonsignificant trend for a delayed onset of ILD in patients who had been treated with methotrexate (OR, 0.54; P = .072).

Methotrexate use is associated with an acute hypersensitivity pneumonitis in patients with RA, explained Patrick Kiely, MBBS, PhD, of St. George’s University Hospitals NHS Foundation Trust in London at the British Society for Rheumatology annual conference. “This is well recognized, it’s very rare [0.43%-1.00%], it’s easy to spot, and usually goes away if you stop methotrexate,” said Dr. Kiely, adding that “it’s not benign, and severe cases can be life threatening.”

Because of the association between methotrexate and pneumonitis, there has been concern that methotrexate may exacerbate or even cause ILD in RA but there are sparse data available to confirm this. The bottom line is that you should not start someone on methotrexate if you think their existing lung capacity is not up to treatment with methotrexate, Dr. Kiely said.

ILD is not always symptomatic in RA, but when it is, it is associated with very poor survival. The lung disease can be present before joint symptoms, Dr. Kiely said. Although less than 10% of cases may be symptomatic, this “is a big deal, because it has a high mortality, with death within 5 years. It’s the second-commonest cause of excess mortality in RA after cardiovascular disease.”

To look at the association between incident RA-ILD and the use of methotrexate, Dr. Kiely and associates analyzed data from ERAS (1986-2001) and ERAN (2002-2013), that together have more than 25 years of follow-up data on patients who were recruited at the first sign of RA symptoms. Patients within these cohorts have been treated according to best practice, and a range of outcomes – including RA-ILD – have been assessed at annual intervals.

In the patients who developed ILD after any csDMARD exposure, older age at RA onset (OR, 1.04; P less than .001) and having ever smoked (OR, 1.91; P = .016) were associated with the development of the lung disease. Incident ILD was also associated with being positive for rheumatoid factor (OR, 2.02; P = .029) at baseline. Being male was also associated with a higher risk for developing ILD, Dr. Kiely reported, as was a longer duration of time between the onset of first RA symptoms and the first secondary care visit. Conversely, the presence of nonrespiratory, major comorbidities at baseline appeared to be protective (OR, 0.62; P = .027).

“We found no association between methotrexate treatment and incident RA-ILD and a possibility that it may be protective,” Dr. Kiely concluded, noting that these data were now published in BMJ Open (2019;9:e028466. doi: 10.1136/bmjopen-2018-028466).

Following Dr. Kiely’s presentation, an audience member asked if the protective effect seen with methotrexate could have been caused by better disease control overall.

Dr. Kiely answered that, up until 2001, the time when ERAS was ongoing, standard practice in the United Kingdom was to use sulfasalazine, but then methotrexate started to be used in higher and higher doses, as seen in ERAN.

The interesting thing is that in ERAN more methotrexate was used in higher doses, but less RA-ILD was seen, Dr. Kiely observed. The overall prevalence of RA-ILD in the later early RA cohort was 3.2% and the median dose of methotrexate used was 20 mg. In ERAS, the prevalence was 4.2% and the median dose of methotrexate used was 10 mg.

There was a suggestion that disease control was slightly better in ERAN than ERAS, but that wasn’t statistically significant, Dr. Kiely said.

So, should a patient with RA and ILD be given methotrexate? There’s no reason not to, Dr. Kiely suggested, based on the evidence shown. Part of the challenge will now be convincing chest physician colleagues that methotrexate is not problematic in terms of causing ILD.

These findings are completely on board with the ILD group’s findings that methotrexate doesn’t cause pulmonary fibrosis in patients with RA, commented Julie Dawson, MD, of St. Helens and Knowsley Teaching Hospitals NHS Trust, St. Helens, England. Her own research, which includes a 10-year follow-up of patients with inflammatory arthritis, has shown that methotrexate does not appear to increase the risk of pulmonary fibrosis.

The study had no specific outside funding. Dr. Kiely reported having no conflicts of interest.

SOURCE: Kiely P et al. Rheumatology. 2019;58(suppl 3), Abstract 009.

BIRMINGHAM, ENGLAND – Data from two early RA inception cohorts provide reassurance that methotrexate does not cause interstitial lung disease and suggest that treatment with methotrexate might even be protective.

Sara Freeman/MDedge News

In the Early RA Study (ERAS) and Early RA Network (ERAN), which together include 2,701 patients with RA, 101 (3.7%) had interstitial lung disease (ILD). There were 92 patients with RA-ILD who had information available on exposure to any conventional synthetic disease-modifying antirheumatic drug (csDMARD); of these, 39 (2.5%) had been exposed to methotrexate (n = 1,578) and 53 (4.8%) to other csDMARDs (n = 1,114).

Multivariate analysis showed that methotrexate exposure was associated with a reduced risk of developing ILD, with an odds ratio of 0.48 (P = .004). In a separate analysis that excluded 25 patients who had ILD before they received any csDMARD therapy (n = 67), there was no association between methotrexate use and ILD (OR, 0.85; P = .578). In fact, there was a nonsignificant trend for a delayed onset of ILD in patients who had been treated with methotrexate (OR, 0.54; P = .072).

Methotrexate use is associated with an acute hypersensitivity pneumonitis in patients with RA, explained Patrick Kiely, MBBS, PhD, of St. George’s University Hospitals NHS Foundation Trust in London at the British Society for Rheumatology annual conference. “This is well recognized, it’s very rare [0.43%-1.00%], it’s easy to spot, and usually goes away if you stop methotrexate,” said Dr. Kiely, adding that “it’s not benign, and severe cases can be life threatening.”

Because of the association between methotrexate and pneumonitis, there has been concern that methotrexate may exacerbate or even cause ILD in RA but there are sparse data available to confirm this. The bottom line is that you should not start someone on methotrexate if you think their existing lung capacity is not up to treatment with methotrexate, Dr. Kiely said.

ILD is not always symptomatic in RA, but when it is, it is associated with very poor survival. The lung disease can be present before joint symptoms, Dr. Kiely said. Although less than 10% of cases may be symptomatic, this “is a big deal, because it has a high mortality, with death within 5 years. It’s the second-commonest cause of excess mortality in RA after cardiovascular disease.”

To look at the association between incident RA-ILD and the use of methotrexate, Dr. Kiely and associates analyzed data from ERAS (1986-2001) and ERAN (2002-2013), that together have more than 25 years of follow-up data on patients who were recruited at the first sign of RA symptoms. Patients within these cohorts have been treated according to best practice, and a range of outcomes – including RA-ILD – have been assessed at annual intervals.

In the patients who developed ILD after any csDMARD exposure, older age at RA onset (OR, 1.04; P less than .001) and having ever smoked (OR, 1.91; P = .016) were associated with the development of the lung disease. Incident ILD was also associated with being positive for rheumatoid factor (OR, 2.02; P = .029) at baseline. Being male was also associated with a higher risk for developing ILD, Dr. Kiely reported, as was a longer duration of time between the onset of first RA symptoms and the first secondary care visit. Conversely, the presence of nonrespiratory, major comorbidities at baseline appeared to be protective (OR, 0.62; P = .027).

“We found no association between methotrexate treatment and incident RA-ILD and a possibility that it may be protective,” Dr. Kiely concluded, noting that these data were now published in BMJ Open (2019;9:e028466. doi: 10.1136/bmjopen-2018-028466).

Following Dr. Kiely’s presentation, an audience member asked if the protective effect seen with methotrexate could have been caused by better disease control overall.

Dr. Kiely answered that, up until 2001, the time when ERAS was ongoing, standard practice in the United Kingdom was to use sulfasalazine, but then methotrexate started to be used in higher and higher doses, as seen in ERAN.

The interesting thing is that in ERAN more methotrexate was used in higher doses, but less RA-ILD was seen, Dr. Kiely observed. The overall prevalence of RA-ILD in the later early RA cohort was 3.2% and the median dose of methotrexate used was 20 mg. In ERAS, the prevalence was 4.2% and the median dose of methotrexate used was 10 mg.

There was a suggestion that disease control was slightly better in ERAN than ERAS, but that wasn’t statistically significant, Dr. Kiely said.

So, should a patient with RA and ILD be given methotrexate? There’s no reason not to, Dr. Kiely suggested, based on the evidence shown. Part of the challenge will now be convincing chest physician colleagues that methotrexate is not problematic in terms of causing ILD.

These findings are completely on board with the ILD group’s findings that methotrexate doesn’t cause pulmonary fibrosis in patients with RA, commented Julie Dawson, MD, of St. Helens and Knowsley Teaching Hospitals NHS Trust, St. Helens, England. Her own research, which includes a 10-year follow-up of patients with inflammatory arthritis, has shown that methotrexate does not appear to increase the risk of pulmonary fibrosis.

The study had no specific outside funding. Dr. Kiely reported having no conflicts of interest.

SOURCE: Kiely P et al. Rheumatology. 2019;58(suppl 3), Abstract 009.

BIRMINGHAM, England – More than half of all patients referred to a fast-track giant cell arteritis (GCA) clinic that offers a walk-in ultrasonography service avoided use of glucocorticoids, according to a report given at the annual conference of the British Society for Rheumatology.

Sara Freeman/MDedge News

The clinic, an initiative run by the University Hospital Coventry and Warwickshire (UHCW) NHS Trust for the past 6 years, provides same-day diagnosis and treatment for suspected GCA.

“Walk-in ultrasound helps to avoid steroids completely in a significant proportion of patients,” said study author and presenter Shirish Dubey, MBBS, a consultant rheumatologist at the UHCW NHS Trust. Of 652 patients seen at the UHCW GCA fast-track clinic between 2014 and 2017, 143 (22%) were diagnosed with GCA. Over 400 had not been exposed to glucocorticoids and 369 (57%) were able to avoid unnecessary glucocorticoid use in the cohort, Dr. Dubey reported.

The old NHS paradigm for managing patients with suspected GCA was that when they presented to their primary care physicians, they would be started on immediate glucocorticoid therapy while waiting for an urgent specialist referral. However, that referral could take anywhere from a couple of days to a couple of weeks to happen, Dr. Dubey explained. Patients would then undergo possible temporal artery biopsy (TAB) and only then, following confirmation of a GCA diagnosis, would a management plan be agreed upon.

UCHW introduced its fast-track pathway for the diagnosis of GCA in mid-2013. The pathway called for patients with suspected GCA aged 50 years or older who had two or more features present, such as an abrupt, new-onset headache or facial pain, scalp pain and tenderness, jaw claudication, or visual symptoms. Primary care physicians could make urgent referrals to the service via an on-call rheumatology trainee or ophthalmology senior house officer.

“Patients are normally steroid-naive and seen on the same day,” Dr. Dubey said. Doppler ultrasound of the temporal artery results in around 80% of diagnoses, with TAB still needed in some cases.

One of the downsides of the fast-track process perhaps is the increasing number of referrals. “One thing we find is that we have become a glorified headache service,” Dr. Dubey said. However, many patients do not have GCA and, when there is a low clinical probability and the ultrasound is negative, the patient is usually reassured and discharged with no need for glucocorticoids. Although the number of referrals have increased – 98 patients in 2014, 154 in 2015, 123 in 2016, and 277 in 2017 – the number of those diagnosed with GCA has remained around the same.

To see how ultrasound was faring in real-life practice, the UHCW NHS Trust team compared Doppler ultrasound findings against the final clinical diagnosis for the period 2014 to 2017. A sensitivity of just under 48% and specificity of 98% was recorded. The positive and negative predictive values were 87% and 88%, respectively.

The specificity of ultrasound was lower than that reported previously in the literature, the UHCW NHS Trust team pointed out in its abstract, but it does compare similarly with other real-world studies. The use of glucocorticoids affected the ultrasound results, with better sensitivity (55%) when these drugs were not used prior to the scan.

The use of TAB versus a clinical diagnosis in 100 patients seen over the same time period showed it had a sensitivity of 37% and a specificity of 100%, with positive and negative predictive values of 100% and 62%. The sensitivity of TAB is again low, Dr. Dubey said, but that could be because TAB is performed only when the diagnosis is uncertain.

This was an unselected cohort of patients, but overall there were good positive and negative predictive values. The UHCW NHS Trust team suggested that ultrasound can assist and reassure clinicians trying to diagnose or exclude GCA in their patients.

Regular multidisciplinary team meetings including rheumatology, ophthalmology, and vascular Doppler physiologists are key to the fast-track service, Dr. Dubey pointed out.

Despite the shortcomings of the retrospective study, Dr. Dubey stressed that the team was confident that none of the patients who had been ruled out as having GCA were subsequently diagnosed as having GCA.

Importantly, he said, the use of ultrasound had made a big difference in cost; the group plans to formally evaluate costs of ultrasound versus TAB.

The study received no commercial funding. Dr. Dubey had no conflicts of interest to disclose.

SOURCE: Pinnell J et al. Rheumatology. 2019;58(suppl 3):Abstract 038.
 

BIRMINGHAM, England – More than half of all patients referred to a fast-track giant cell arteritis (GCA) clinic that offers a walk-in ultrasonography service avoided use of glucocorticoids, according to a report given at the annual conference of the British Society for Rheumatology.

Sara Freeman/MDedge News

The clinic, an initiative run by the University Hospital Coventry and Warwickshire (UHCW) NHS Trust for the past 6 years, provides same-day diagnosis and treatment for suspected GCA.

“Walk-in ultrasound helps to avoid steroids completely in a significant proportion of patients,” said study author and presenter Shirish Dubey, MBBS, a consultant rheumatologist at the UHCW NHS Trust. Of 652 patients seen at the UHCW GCA fast-track clinic between 2014 and 2017, 143 (22%) were diagnosed with GCA. Over 400 had not been exposed to glucocorticoids and 369 (57%) were able to avoid unnecessary glucocorticoid use in the cohort, Dr. Dubey reported.

The old NHS paradigm for managing patients with suspected GCA was that when they presented to their primary care physicians, they would be started on immediate glucocorticoid therapy while waiting for an urgent specialist referral. However, that referral could take anywhere from a couple of days to a couple of weeks to happen, Dr. Dubey explained. Patients would then undergo possible temporal artery biopsy (TAB) and only then, following confirmation of a GCA diagnosis, would a management plan be agreed upon.

UCHW introduced its fast-track pathway for the diagnosis of GCA in mid-2013. The pathway called for patients with suspected GCA aged 50 years or older who had two or more features present, such as an abrupt, new-onset headache or facial pain, scalp pain and tenderness, jaw claudication, or visual symptoms. Primary care physicians could make urgent referrals to the service via an on-call rheumatology trainee or ophthalmology senior house officer.

“Patients are normally steroid-naive and seen on the same day,” Dr. Dubey said. Doppler ultrasound of the temporal artery results in around 80% of diagnoses, with TAB still needed in some cases.

One of the downsides of the fast-track process perhaps is the increasing number of referrals. “One thing we find is that we have become a glorified headache service,” Dr. Dubey said. However, many patients do not have GCA and, when there is a low clinical probability and the ultrasound is negative, the patient is usually reassured and discharged with no need for glucocorticoids. Although the number of referrals have increased – 98 patients in 2014, 154 in 2015, 123 in 2016, and 277 in 2017 – the number of those diagnosed with GCA has remained around the same.

To see how ultrasound was faring in real-life practice, the UHCW NHS Trust team compared Doppler ultrasound findings against the final clinical diagnosis for the period 2014 to 2017. A sensitivity of just under 48% and specificity of 98% was recorded. The positive and negative predictive values were 87% and 88%, respectively.

The specificity of ultrasound was lower than that reported previously in the literature, the UHCW NHS Trust team pointed out in its abstract, but it does compare similarly with other real-world studies. The use of glucocorticoids affected the ultrasound results, with better sensitivity (55%) when these drugs were not used prior to the scan.

The use of TAB versus a clinical diagnosis in 100 patients seen over the same time period showed it had a sensitivity of 37% and a specificity of 100%, with positive and negative predictive values of 100% and 62%. The sensitivity of TAB is again low, Dr. Dubey said, but that could be because TAB is performed only when the diagnosis is uncertain.

This was an unselected cohort of patients, but overall there were good positive and negative predictive values. The UHCW NHS Trust team suggested that ultrasound can assist and reassure clinicians trying to diagnose or exclude GCA in their patients.

Regular multidisciplinary team meetings including rheumatology, ophthalmology, and vascular Doppler physiologists are key to the fast-track service, Dr. Dubey pointed out.

Despite the shortcomings of the retrospective study, Dr. Dubey stressed that the team was confident that none of the patients who had been ruled out as having GCA were subsequently diagnosed as having GCA.

Importantly, he said, the use of ultrasound had made a big difference in cost; the group plans to formally evaluate costs of ultrasound versus TAB.

The study received no commercial funding. Dr. Dubey had no conflicts of interest to disclose.

SOURCE: Pinnell J et al. Rheumatology. 2019;58(suppl 3):Abstract 038.
 

BIRMINGHAM, England – More than half of all patients referred to a fast-track giant cell arteritis (GCA) clinic that offers a walk-in ultrasonography service avoided use of glucocorticoids, according to a report given at the annual conference of the British Society for Rheumatology.

Sara Freeman/MDedge News

The clinic, an initiative run by the University Hospital Coventry and Warwickshire (UHCW) NHS Trust for the past 6 years, provides same-day diagnosis and treatment for suspected GCA.

“Walk-in ultrasound helps to avoid steroids completely in a significant proportion of patients,” said study author and presenter Shirish Dubey, MBBS, a consultant rheumatologist at the UHCW NHS Trust. Of 652 patients seen at the UHCW GCA fast-track clinic between 2014 and 2017, 143 (22%) were diagnosed with GCA. Over 400 had not been exposed to glucocorticoids and 369 (57%) were able to avoid unnecessary glucocorticoid use in the cohort, Dr. Dubey reported.

The old NHS paradigm for managing patients with suspected GCA was that when they presented to their primary care physicians, they would be started on immediate glucocorticoid therapy while waiting for an urgent specialist referral. However, that referral could take anywhere from a couple of days to a couple of weeks to happen, Dr. Dubey explained. Patients would then undergo possible temporal artery biopsy (TAB) and only then, following confirmation of a GCA diagnosis, would a management plan be agreed upon.

UCHW introduced its fast-track pathway for the diagnosis of GCA in mid-2013. The pathway called for patients with suspected GCA aged 50 years or older who had two or more features present, such as an abrupt, new-onset headache or facial pain, scalp pain and tenderness, jaw claudication, or visual symptoms. Primary care physicians could make urgent referrals to the service via an on-call rheumatology trainee or ophthalmology senior house officer.

“Patients are normally steroid-naive and seen on the same day,” Dr. Dubey said. Doppler ultrasound of the temporal artery results in around 80% of diagnoses, with TAB still needed in some cases.

One of the downsides of the fast-track process perhaps is the increasing number of referrals. “One thing we find is that we have become a glorified headache service,” Dr. Dubey said. However, many patients do not have GCA and, when there is a low clinical probability and the ultrasound is negative, the patient is usually reassured and discharged with no need for glucocorticoids. Although the number of referrals have increased – 98 patients in 2014, 154 in 2015, 123 in 2016, and 277 in 2017 – the number of those diagnosed with GCA has remained around the same.

To see how ultrasound was faring in real-life practice, the UHCW NHS Trust team compared Doppler ultrasound findings against the final clinical diagnosis for the period 2014 to 2017. A sensitivity of just under 48% and specificity of 98% was recorded. The positive and negative predictive values were 87% and 88%, respectively.

The specificity of ultrasound was lower than that reported previously in the literature, the UHCW NHS Trust team pointed out in its abstract, but it does compare similarly with other real-world studies. The use of glucocorticoids affected the ultrasound results, with better sensitivity (55%) when these drugs were not used prior to the scan.

The use of TAB versus a clinical diagnosis in 100 patients seen over the same time period showed it had a sensitivity of 37% and a specificity of 100%, with positive and negative predictive values of 100% and 62%. The sensitivity of TAB is again low, Dr. Dubey said, but that could be because TAB is performed only when the diagnosis is uncertain.

This was an unselected cohort of patients, but overall there were good positive and negative predictive values. The UHCW NHS Trust team suggested that ultrasound can assist and reassure clinicians trying to diagnose or exclude GCA in their patients.

Regular multidisciplinary team meetings including rheumatology, ophthalmology, and vascular Doppler physiologists are key to the fast-track service, Dr. Dubey pointed out.

Despite the shortcomings of the retrospective study, Dr. Dubey stressed that the team was confident that none of the patients who had been ruled out as having GCA were subsequently diagnosed as having GCA.

Importantly, he said, the use of ultrasound had made a big difference in cost; the group plans to formally evaluate costs of ultrasound versus TAB.

The study received no commercial funding. Dr. Dubey had no conflicts of interest to disclose.

SOURCE: Pinnell J et al. Rheumatology. 2019;58(suppl 3):Abstract 038.
 

BIRMINGHAM, ENGLAND – Intradermal delivery of a tumor necrosis factor inhibitor (TNFi) could offer patients with discoid lupus erythematosus (DLE) a much-needed additional treatment option, according to results of a phase 2, “proof-of-concept” study.

Sara Freeman/MDedge News

Overall, 14 (56%) of the 25 patients in the study achieved a 20% or greater reduction in disease activity from baseline to week 12 via intradermal injection of etanercept (Enbrel), which was assessed via the modified limited Score of Activity and Damage in DLE (ML-SADDLE). About half (48%) and one-fifth (20%) also achieved greater reductions of 50% and 70%, respectively.

“Discoid lupus is a chronic form of cutaneous lupus. Usually it occurs in visible areas like the face and scalp, causing scarring, so it’s really disabling and affects patients’ quality of life,” observed the lead study investigator Md Yuzaiful Md Yusof, MBChB, PhD, NIHR Academic Clinical Lecturer at the University of Leeds, England.

“It’s also one of the most resistant manifestations of lupus,” he said during a poster presentation at the annual conference of the British Society for Rheumatology. “Usually, when people have discoid lupus, the dermatologist gives antimalarial treatment, but only 50% of people respond to these drugs. So, what happens to the rest of them?” Basically, it is trial and error, Dr. Md Yusof said; some patients may be given disease-modifying antirheumatic drugs and in some patients this may work well, but in others there may be toxicity that contraindicates treatment.

B-cell therapy with rituximab (Rituxan) has not been successful, he said. In a previous study of 35 patients with refractory discoid lupus, none of the patients responded to rituximab and half of them actually flared after taking the drug.

There is a pathologic case for using anti-TNF therapy in DLE, but the use of TNFis is not without concern. Such treatment can increase antinuclear antibody production and make lupus worse. “In order to overcome this, as the lesion is quite small, we don’t need to use a systemic approach,” Dr. Md Yusof explained in an interview. “If you give directly, it should just be confined to the lesion and not absorbed, that’s the whole idea of thinking outside the box.” He noted that if it worked, such treatment would be for inducing remission and not for maintenance.

The study, “Targeted therapy using intradermal injection of etanercept for remission induction in discoid lupus erythematosus” (TARGET-DLE) was designed to test the validity of using intradermal rather than subcutaneous TNFi therapy in patients with discoid lupus.

Dr. Md Yusof noted that only 25 patients needed to be recruited into the single-arm, prospective trial as a “Simon’s two-stage minimized design” was used (Control Clin Trials. 1989;10[1]:1-10). This involved treating the first few patients to see if a response occurred and if it did, carrying on with treating the others, but if no response occurred in at least two patients, the trial would stop completely.

Adult patients were eligible for inclusion if they had one or more active DLE lesions and had not responded to antimalarial treatment. Stable doses of DMARDs and up to 10 mg of oral prednisolone daily was permitted if already being taken prior to entering the study.

Etanercept was injected intradermally around the most symptomatic lesion once a week for up to 12 weeks. The dosage was determined based on the radius of the selected discoid lesion. Over an 18-month period, all 25 patients were recruited, including 18 women. The median age of patients was 47 years, and six had systemic lupus erythematosus. The median number of prior DMARDs was 5 but ranged from 1 to 16, indicating a very resistant patient population.

The primary endpoint was at least 6 of the 25 patients having at least a 20% reduction in ML-SADDLE at week 12; 14 (56%) patients achieved this.

“We didn’t use CLASI [Cutaneous Lupus Area and Severity Index Activity Score] because that only includes erythema and atrophy,” Dr. Md Yusof explained. “In discoid lupus, induration is quite important as well, so that’s why we used ML-SADDLE. We called it ‘modified limited’ because the original SADDLE score is based on the whole organ score, but we only calculated the one lesion that we wanted to treat.”

In addition to meeting the primary endpoint, several secondary endpoints were met, including significant improvements in scores on visual analog scales as determined by pre- and posttreatment scoring by physicians (53.1 mm vs. 23.2 mm; P less than .001) and patients (56.9 mm vs. 29.7 mm; P = .001). Mean Dermatology Life Quality Index (DLQI) score significantly improved between pre- and post treatment, as did blood perfusion under the skin based on laser Doppler imaging and infrared thermography. However, no difference was seen with optical coherence tomography.

“There were only four grade 3/4 toxicities, and importantly, none of the SLE patients got worse, and none with DLE only converted into SLE,” Dr. Md Yusof reported. Of the four grade 3/4 adverse events, two were chest infections, one was heart failure, and one was a worsening of chilblains.

“It was a full-powered phase 2 trial, and because it was positive, now we can go to phase 3 trial,” he added.

Before conducting a phase 3 trial, however, Dr. Md Yusof wants to refine how the TNFi is delivered. Perhaps an intradermal patch with microneedles could be used. This would be left on the skin for a short amount of time to allow drug delivery and then removed. It could help ensure that all patients comply with treatment and perhaps even self-administer, he noted.

“The median compliance rate was 80%, which is not too bad, but I think when we come to run a phase 3 trial, I’m looking to improve the drug delivery,” he said. Changing the delivery method will need to be validated before a phase 3 trial can be started.

The study was not commercially funded. Dr. Md Yusof had no disclosures. Pfizer provided the study drug free of charge.

SOURCE: Md Yusof MY et al. Rheumatology. 2019;58(suppl 3): Abstract 244. doi: 10.1093/rheumatology/kez107.060.

BIRMINGHAM, ENGLAND – Intradermal delivery of a tumor necrosis factor inhibitor (TNFi) could offer patients with discoid lupus erythematosus (DLE) a much-needed additional treatment option, according to results of a phase 2, “proof-of-concept” study.

Sara Freeman/MDedge News

Overall, 14 (56%) of the 25 patients in the study achieved a 20% or greater reduction in disease activity from baseline to week 12 via intradermal injection of etanercept (Enbrel), which was assessed via the modified limited Score of Activity and Damage in DLE (ML-SADDLE). About half (48%) and one-fifth (20%) also achieved greater reductions of 50% and 70%, respectively.

“Discoid lupus is a chronic form of cutaneous lupus. Usually it occurs in visible areas like the face and scalp, causing scarring, so it’s really disabling and affects patients’ quality of life,” observed the lead study investigator Md Yuzaiful Md Yusof, MBChB, PhD, NIHR Academic Clinical Lecturer at the University of Leeds, England.

“It’s also one of the most resistant manifestations of lupus,” he said during a poster presentation at the annual conference of the British Society for Rheumatology. “Usually, when people have discoid lupus, the dermatologist gives antimalarial treatment, but only 50% of people respond to these drugs. So, what happens to the rest of them?” Basically, it is trial and error, Dr. Md Yusof said; some patients may be given disease-modifying antirheumatic drugs and in some patients this may work well, but in others there may be toxicity that contraindicates treatment.

B-cell therapy with rituximab (Rituxan) has not been successful, he said. In a previous study of 35 patients with refractory discoid lupus, none of the patients responded to rituximab and half of them actually flared after taking the drug.

There is a pathologic case for using anti-TNF therapy in DLE, but the use of TNFis is not without concern. Such treatment can increase antinuclear antibody production and make lupus worse. “In order to overcome this, as the lesion is quite small, we don’t need to use a systemic approach,” Dr. Md Yusof explained in an interview. “If you give directly, it should just be confined to the lesion and not absorbed, that’s the whole idea of thinking outside the box.” He noted that if it worked, such treatment would be for inducing remission and not for maintenance.

The study, “Targeted therapy using intradermal injection of etanercept for remission induction in discoid lupus erythematosus” (TARGET-DLE) was designed to test the validity of using intradermal rather than subcutaneous TNFi therapy in patients with discoid lupus.

Dr. Md Yusof noted that only 25 patients needed to be recruited into the single-arm, prospective trial as a “Simon’s two-stage minimized design” was used (Control Clin Trials. 1989;10[1]:1-10). This involved treating the first few patients to see if a response occurred and if it did, carrying on with treating the others, but if no response occurred in at least two patients, the trial would stop completely.

Adult patients were eligible for inclusion if they had one or more active DLE lesions and had not responded to antimalarial treatment. Stable doses of DMARDs and up to 10 mg of oral prednisolone daily was permitted if already being taken prior to entering the study.

Etanercept was injected intradermally around the most symptomatic lesion once a week for up to 12 weeks. The dosage was determined based on the radius of the selected discoid lesion. Over an 18-month period, all 25 patients were recruited, including 18 women. The median age of patients was 47 years, and six had systemic lupus erythematosus. The median number of prior DMARDs was 5 but ranged from 1 to 16, indicating a very resistant patient population.

The primary endpoint was at least 6 of the 25 patients having at least a 20% reduction in ML-SADDLE at week 12; 14 (56%) patients achieved this.

“We didn’t use CLASI [Cutaneous Lupus Area and Severity Index Activity Score] because that only includes erythema and atrophy,” Dr. Md Yusof explained. “In discoid lupus, induration is quite important as well, so that’s why we used ML-SADDLE. We called it ‘modified limited’ because the original SADDLE score is based on the whole organ score, but we only calculated the one lesion that we wanted to treat.”

In addition to meeting the primary endpoint, several secondary endpoints were met, including significant improvements in scores on visual analog scales as determined by pre- and posttreatment scoring by physicians (53.1 mm vs. 23.2 mm; P less than .001) and patients (56.9 mm vs. 29.7 mm; P = .001). Mean Dermatology Life Quality Index (DLQI) score significantly improved between pre- and post treatment, as did blood perfusion under the skin based on laser Doppler imaging and infrared thermography. However, no difference was seen with optical coherence tomography.

“There were only four grade 3/4 toxicities, and importantly, none of the SLE patients got worse, and none with DLE only converted into SLE,” Dr. Md Yusof reported. Of the four grade 3/4 adverse events, two were chest infections, one was heart failure, and one was a worsening of chilblains.

“It was a full-powered phase 2 trial, and because it was positive, now we can go to phase 3 trial,” he added.

Before conducting a phase 3 trial, however, Dr. Md Yusof wants to refine how the TNFi is delivered. Perhaps an intradermal patch with microneedles could be used. This would be left on the skin for a short amount of time to allow drug delivery and then removed. It could help ensure that all patients comply with treatment and perhaps even self-administer, he noted.

“The median compliance rate was 80%, which is not too bad, but I think when we come to run a phase 3 trial, I’m looking to improve the drug delivery,” he said. Changing the delivery method will need to be validated before a phase 3 trial can be started.

The study was not commercially funded. Dr. Md Yusof had no disclosures. Pfizer provided the study drug free of charge.

SOURCE: Md Yusof MY et al. Rheumatology. 2019;58(suppl 3): Abstract 244. doi: 10.1093/rheumatology/kez107.060.

BIRMINGHAM, ENGLAND – Intradermal delivery of a tumor necrosis factor inhibitor (TNFi) could offer patients with discoid lupus erythematosus (DLE) a much-needed additional treatment option, according to results of a phase 2, “proof-of-concept” study.

Sara Freeman/MDedge News

Overall, 14 (56%) of the 25 patients in the study achieved a 20% or greater reduction in disease activity from baseline to week 12 via intradermal injection of etanercept (Enbrel), which was assessed via the modified limited Score of Activity and Damage in DLE (ML-SADDLE). About half (48%) and one-fifth (20%) also achieved greater reductions of 50% and 70%, respectively.

“Discoid lupus is a chronic form of cutaneous lupus. Usually it occurs in visible areas like the face and scalp, causing scarring, so it’s really disabling and affects patients’ quality of life,” observed the lead study investigator Md Yuzaiful Md Yusof, MBChB, PhD, NIHR Academic Clinical Lecturer at the University of Leeds, England.

“It’s also one of the most resistant manifestations of lupus,” he said during a poster presentation at the annual conference of the British Society for Rheumatology. “Usually, when people have discoid lupus, the dermatologist gives antimalarial treatment, but only 50% of people respond to these drugs. So, what happens to the rest of them?” Basically, it is trial and error, Dr. Md Yusof said; some patients may be given disease-modifying antirheumatic drugs and in some patients this may work well, but in others there may be toxicity that contraindicates treatment.

B-cell therapy with rituximab (Rituxan) has not been successful, he said. In a previous study of 35 patients with refractory discoid lupus, none of the patients responded to rituximab and half of them actually flared after taking the drug.

There is a pathologic case for using anti-TNF therapy in DLE, but the use of TNFis is not without concern. Such treatment can increase antinuclear antibody production and make lupus worse. “In order to overcome this, as the lesion is quite small, we don’t need to use a systemic approach,” Dr. Md Yusof explained in an interview. “If you give directly, it should just be confined to the lesion and not absorbed, that’s the whole idea of thinking outside the box.” He noted that if it worked, such treatment would be for inducing remission and not for maintenance.

The study, “Targeted therapy using intradermal injection of etanercept for remission induction in discoid lupus erythematosus” (TARGET-DLE) was designed to test the validity of using intradermal rather than subcutaneous TNFi therapy in patients with discoid lupus.

Dr. Md Yusof noted that only 25 patients needed to be recruited into the single-arm, prospective trial as a “Simon’s two-stage minimized design” was used (Control Clin Trials. 1989;10[1]:1-10). This involved treating the first few patients to see if a response occurred and if it did, carrying on with treating the others, but if no response occurred in at least two patients, the trial would stop completely.

Adult patients were eligible for inclusion if they had one or more active DLE lesions and had not responded to antimalarial treatment. Stable doses of DMARDs and up to 10 mg of oral prednisolone daily was permitted if already being taken prior to entering the study.

Etanercept was injected intradermally around the most symptomatic lesion once a week for up to 12 weeks. The dosage was determined based on the radius of the selected discoid lesion. Over an 18-month period, all 25 patients were recruited, including 18 women. The median age of patients was 47 years, and six had systemic lupus erythematosus. The median number of prior DMARDs was 5 but ranged from 1 to 16, indicating a very resistant patient population.

The primary endpoint was at least 6 of the 25 patients having at least a 20% reduction in ML-SADDLE at week 12; 14 (56%) patients achieved this.

“We didn’t use CLASI [Cutaneous Lupus Area and Severity Index Activity Score] because that only includes erythema and atrophy,” Dr. Md Yusof explained. “In discoid lupus, induration is quite important as well, so that’s why we used ML-SADDLE. We called it ‘modified limited’ because the original SADDLE score is based on the whole organ score, but we only calculated the one lesion that we wanted to treat.”

In addition to meeting the primary endpoint, several secondary endpoints were met, including significant improvements in scores on visual analog scales as determined by pre- and posttreatment scoring by physicians (53.1 mm vs. 23.2 mm; P less than .001) and patients (56.9 mm vs. 29.7 mm; P = .001). Mean Dermatology Life Quality Index (DLQI) score significantly improved between pre- and post treatment, as did blood perfusion under the skin based on laser Doppler imaging and infrared thermography. However, no difference was seen with optical coherence tomography.

“There were only four grade 3/4 toxicities, and importantly, none of the SLE patients got worse, and none with DLE only converted into SLE,” Dr. Md Yusof reported. Of the four grade 3/4 adverse events, two were chest infections, one was heart failure, and one was a worsening of chilblains.

“It was a full-powered phase 2 trial, and because it was positive, now we can go to phase 3 trial,” he added.

Before conducting a phase 3 trial, however, Dr. Md Yusof wants to refine how the TNFi is delivered. Perhaps an intradermal patch with microneedles could be used. This would be left on the skin for a short amount of time to allow drug delivery and then removed. It could help ensure that all patients comply with treatment and perhaps even self-administer, he noted.

“The median compliance rate was 80%, which is not too bad, but I think when we come to run a phase 3 trial, I’m looking to improve the drug delivery,” he said. Changing the delivery method will need to be validated before a phase 3 trial can be started.

The study was not commercially funded. Dr. Md Yusof had no disclosures. Pfizer provided the study drug free of charge.

SOURCE: Md Yusof MY et al. Rheumatology. 2019;58(suppl 3): Abstract 244. doi: 10.1093/rheumatology/kez107.060.

BIRMINGHAM, ENGLAND – An evidence-based approach coupled with expert consensus has been used to determine the best way to use MRI for the diagnosis of axial spondyloarthritis (axSpA).

Working under the auspices of the British Society for Spondyloarthritis (BRITSpA), a task force of nine rheumatologists and nine musculoskeletal radiologists with an interest in axSpA developed a set of seven recommendations that provide guidance on how to best to acquire and then interpret MRI images of the spine and sacroiliac joints.

The recommendations, which were published online (Rheumatology. 2019 May 2. doi: 10.1093/rheumatology/kez173), cover how to perform MRI when axSpA is suspected, such as by imaging both the sacroiliac joints and the spine, and provide guidance on the sequences and order of MRI planes to be used, and what features may increase the diagnostic confidence of axSpA.

The recommendations are as follows:

• When requesting an MRI for suspected axSpA, imaging of both the sacroiliac joints and the spine is recommended.

• T1-weighted and fat-suppressed, fluid-sensitive sequences are recommended for suspected axSpA.

• The minimum protocol when requesting an MRI for suspected axSpA should include sagittal images of the spine with extended lateral coverage and images of the sacroiliac joints that are in an oblique coronal plane to the joint.

• In the sacroiliac joints, the presence of bone marrow edema, fatty infiltration, or erosion is suggestive of the diagnosis of axSpA. The presence of more than one of these features increases the diagnostic confidence of axSpA.

• In the spine, the presence of multiple corner inflammatory lesions and/or multiple corner fatty lesions increases the diagnostic confidence of axSpA.

• In the sacroiliac joints and/or spine, the presence of characteristic new bone formation increases the diagnostic confidence of axSpA.

• The full range and combination of active and structural lesions of the sacroiliac joints and spine should be taken into account when deciding if the MRI scan is suggestive of axSpA or not.

The recommendations “are intended to standardize practice around the use of MRI,” said Alexis Jones, MBBS, MS (Rheumatology), a senior clinical research fellow at University College London Hospitals NHS Foundation Trust. She presented the recommendations on behalf of the expert task force at the annual conference of the British Society for Rheumatology.

“MRI has become an essential tool in axial spondyloarthritis. It facilitates earlier diagnoses and therefore has allowed for earlier initiation of treatment. It can be used to monitor the burden of inflammation and may predict response to therapy,” Dr. Jones said. Despite this, “there is significant inconsistency in the use of MRI” in clinical practice.

For instance, a survey performed in the United Kingdom (J Rheumatol. 2017;44[6]:780-5) highlighted the need for better collaboration between rheumatology and radiology departments to identify axSpA MRI lesions and develop appropriate protocols.

That survey showed that a quarter of radiologists were not aware of the term axSpA, and just 31% and 25%, respectively, were aware of Assessment of Spondyloarthritis international Society (ASAS) criteria for a positive MRI of the sacroiliac joints and spine. Furthermore, 18% of radiologists did not recognize bone marrow edema as a diagnostic feature of axSpA.

The heterogeneity in the performance of MRI in clinical practice could lead to a delay in diagnosis and potentially misdiagnosis, the task force’s lead author and consultant rheumatologist, Pedro Machado, MD, said in an interview.

“I think everyone has been focusing on demonstrating the value of MRI in the condition but then they forgot to look at the standardization aspect,” said Dr. Machado, who works at University College Hospital and the National Hospital for Neurology and Neurosurgery in London.

With that in mind, the BRITSpA-endorsed task force was set up and met to determine the scope of the recommendations. They looked at the evidence for the use of MRI in the diagnosis of axSpA and used two overarching principles to draft the recommendations: 1) the diagnosis of axSpA is based on clinical, laboratory, and imaging features; 2) Some patients with axSpA have isolated inflammation of the sacroiliac joints or spine.

“All of the recommendations were met with a high level of agreement, indicating a strong consensus” among rheumatologists and radiologists, Dr. Jones noted.

“These recommendations can be immediately applied to clinical practice,” said Dr. Machado, who noted that they should standardize practice and decrease heterogeneity around the use of MRI. “This will help ensure a more informed and consistent approach to the diagnosis of axSpA.”

One of the potential impacts of the recommendations, if followed, is that they may actually help to reduce health care costs, Dr. Machado suggested, because an optimized protocol would be used, making MRI more cost effective by not including sequences that do not add value in the condition.

The next task is to share the recommendations more widely and make sure they are applied in clinical practice.

A systematic literature review on which the recommendations were based was published simultaneously with the conference presentation (Rheumatology. 2019 May 2. doi: 10.1093/rheumatology/kez172).

The work was supported by BRITSpA. The authors had no relevant disclosures.

SOURCE: Bray TJP et al. Rheumatology 2019;58(suppl 3): Abstract 033. doi: 10.1093/rheumatology/kez105.032.

BIRMINGHAM, ENGLAND – An evidence-based approach coupled with expert consensus has been used to determine the best way to use MRI for the diagnosis of axial spondyloarthritis (axSpA).

Working under the auspices of the British Society for Spondyloarthritis (BRITSpA), a task force of nine rheumatologists and nine musculoskeletal radiologists with an interest in axSpA developed a set of seven recommendations that provide guidance on how to best to acquire and then interpret MRI images of the spine and sacroiliac joints.

The recommendations, which were published online (Rheumatology. 2019 May 2. doi: 10.1093/rheumatology/kez173), cover how to perform MRI when axSpA is suspected, such as by imaging both the sacroiliac joints and the spine, and provide guidance on the sequences and order of MRI planes to be used, and what features may increase the diagnostic confidence of axSpA.

The recommendations are as follows:

• When requesting an MRI for suspected axSpA, imaging of both the sacroiliac joints and the spine is recommended.

• T1-weighted and fat-suppressed, fluid-sensitive sequences are recommended for suspected axSpA.

• The minimum protocol when requesting an MRI for suspected axSpA should include sagittal images of the spine with extended lateral coverage and images of the sacroiliac joints that are in an oblique coronal plane to the joint.

• In the sacroiliac joints, the presence of bone marrow edema, fatty infiltration, or erosion is suggestive of the diagnosis of axSpA. The presence of more than one of these features increases the diagnostic confidence of axSpA.

• In the spine, the presence of multiple corner inflammatory lesions and/or multiple corner fatty lesions increases the diagnostic confidence of axSpA.

• In the sacroiliac joints and/or spine, the presence of characteristic new bone formation increases the diagnostic confidence of axSpA.

• The full range and combination of active and structural lesions of the sacroiliac joints and spine should be taken into account when deciding if the MRI scan is suggestive of axSpA or not.

The recommendations “are intended to standardize practice around the use of MRI,” said Alexis Jones, MBBS, MS (Rheumatology), a senior clinical research fellow at University College London Hospitals NHS Foundation Trust. She presented the recommendations on behalf of the expert task force at the annual conference of the British Society for Rheumatology.

“MRI has become an essential tool in axial spondyloarthritis. It facilitates earlier diagnoses and therefore has allowed for earlier initiation of treatment. It can be used to monitor the burden of inflammation and may predict response to therapy,” Dr. Jones said. Despite this, “there is significant inconsistency in the use of MRI” in clinical practice.

For instance, a survey performed in the United Kingdom (J Rheumatol. 2017;44[6]:780-5) highlighted the need for better collaboration between rheumatology and radiology departments to identify axSpA MRI lesions and develop appropriate protocols.

That survey showed that a quarter of radiologists were not aware of the term axSpA, and just 31% and 25%, respectively, were aware of Assessment of Spondyloarthritis international Society (ASAS) criteria for a positive MRI of the sacroiliac joints and spine. Furthermore, 18% of radiologists did not recognize bone marrow edema as a diagnostic feature of axSpA.

The heterogeneity in the performance of MRI in clinical practice could lead to a delay in diagnosis and potentially misdiagnosis, the task force’s lead author and consultant rheumatologist, Pedro Machado, MD, said in an interview.

“I think everyone has been focusing on demonstrating the value of MRI in the condition but then they forgot to look at the standardization aspect,” said Dr. Machado, who works at University College Hospital and the National Hospital for Neurology and Neurosurgery in London.

With that in mind, the BRITSpA-endorsed task force was set up and met to determine the scope of the recommendations. They looked at the evidence for the use of MRI in the diagnosis of axSpA and used two overarching principles to draft the recommendations: 1) the diagnosis of axSpA is based on clinical, laboratory, and imaging features; 2) Some patients with axSpA have isolated inflammation of the sacroiliac joints or spine.

“All of the recommendations were met with a high level of agreement, indicating a strong consensus” among rheumatologists and radiologists, Dr. Jones noted.

“These recommendations can be immediately applied to clinical practice,” said Dr. Machado, who noted that they should standardize practice and decrease heterogeneity around the use of MRI. “This will help ensure a more informed and consistent approach to the diagnosis of axSpA.”

One of the potential impacts of the recommendations, if followed, is that they may actually help to reduce health care costs, Dr. Machado suggested, because an optimized protocol would be used, making MRI more cost effective by not including sequences that do not add value in the condition.

The next task is to share the recommendations more widely and make sure they are applied in clinical practice.

A systematic literature review on which the recommendations were based was published simultaneously with the conference presentation (Rheumatology. 2019 May 2. doi: 10.1093/rheumatology/kez172).

The work was supported by BRITSpA. The authors had no relevant disclosures.

SOURCE: Bray TJP et al. Rheumatology 2019;58(suppl 3): Abstract 033. doi: 10.1093/rheumatology/kez105.032.

BIRMINGHAM, ENGLAND – An evidence-based approach coupled with expert consensus has been used to determine the best way to use MRI for the diagnosis of axial spondyloarthritis (axSpA).

Working under the auspices of the British Society for Spondyloarthritis (BRITSpA), a task force of nine rheumatologists and nine musculoskeletal radiologists with an interest in axSpA developed a set of seven recommendations that provide guidance on how to best to acquire and then interpret MRI images of the spine and sacroiliac joints.

The recommendations, which were published online (Rheumatology. 2019 May 2. doi: 10.1093/rheumatology/kez173), cover how to perform MRI when axSpA is suspected, such as by imaging both the sacroiliac joints and the spine, and provide guidance on the sequences and order of MRI planes to be used, and what features may increase the diagnostic confidence of axSpA.

The recommendations are as follows:

• When requesting an MRI for suspected axSpA, imaging of both the sacroiliac joints and the spine is recommended.

• T1-weighted and fat-suppressed, fluid-sensitive sequences are recommended for suspected axSpA.

• The minimum protocol when requesting an MRI for suspected axSpA should include sagittal images of the spine with extended lateral coverage and images of the sacroiliac joints that are in an oblique coronal plane to the joint.

• In the sacroiliac joints, the presence of bone marrow edema, fatty infiltration, or erosion is suggestive of the diagnosis of axSpA. The presence of more than one of these features increases the diagnostic confidence of axSpA.

• In the spine, the presence of multiple corner inflammatory lesions and/or multiple corner fatty lesions increases the diagnostic confidence of axSpA.

• In the sacroiliac joints and/or spine, the presence of characteristic new bone formation increases the diagnostic confidence of axSpA.

• The full range and combination of active and structural lesions of the sacroiliac joints and spine should be taken into account when deciding if the MRI scan is suggestive of axSpA or not.

The recommendations “are intended to standardize practice around the use of MRI,” said Alexis Jones, MBBS, MS (Rheumatology), a senior clinical research fellow at University College London Hospitals NHS Foundation Trust. She presented the recommendations on behalf of the expert task force at the annual conference of the British Society for Rheumatology.

“MRI has become an essential tool in axial spondyloarthritis. It facilitates earlier diagnoses and therefore has allowed for earlier initiation of treatment. It can be used to monitor the burden of inflammation and may predict response to therapy,” Dr. Jones said. Despite this, “there is significant inconsistency in the use of MRI” in clinical practice.

For instance, a survey performed in the United Kingdom (J Rheumatol. 2017;44[6]:780-5) highlighted the need for better collaboration between rheumatology and radiology departments to identify axSpA MRI lesions and develop appropriate protocols.

That survey showed that a quarter of radiologists were not aware of the term axSpA, and just 31% and 25%, respectively, were aware of Assessment of Spondyloarthritis international Society (ASAS) criteria for a positive MRI of the sacroiliac joints and spine. Furthermore, 18% of radiologists did not recognize bone marrow edema as a diagnostic feature of axSpA.

The heterogeneity in the performance of MRI in clinical practice could lead to a delay in diagnosis and potentially misdiagnosis, the task force’s lead author and consultant rheumatologist, Pedro Machado, MD, said in an interview.

“I think everyone has been focusing on demonstrating the value of MRI in the condition but then they forgot to look at the standardization aspect,” said Dr. Machado, who works at University College Hospital and the National Hospital for Neurology and Neurosurgery in London.

With that in mind, the BRITSpA-endorsed task force was set up and met to determine the scope of the recommendations. They looked at the evidence for the use of MRI in the diagnosis of axSpA and used two overarching principles to draft the recommendations: 1) the diagnosis of axSpA is based on clinical, laboratory, and imaging features; 2) Some patients with axSpA have isolated inflammation of the sacroiliac joints or spine.

“All of the recommendations were met with a high level of agreement, indicating a strong consensus” among rheumatologists and radiologists, Dr. Jones noted.

“These recommendations can be immediately applied to clinical practice,” said Dr. Machado, who noted that they should standardize practice and decrease heterogeneity around the use of MRI. “This will help ensure a more informed and consistent approach to the diagnosis of axSpA.”

One of the potential impacts of the recommendations, if followed, is that they may actually help to reduce health care costs, Dr. Machado suggested, because an optimized protocol would be used, making MRI more cost effective by not including sequences that do not add value in the condition.

The next task is to share the recommendations more widely and make sure they are applied in clinical practice.

A systematic literature review on which the recommendations were based was published simultaneously with the conference presentation (Rheumatology. 2019 May 2. doi: 10.1093/rheumatology/kez172).

The work was supported by BRITSpA. The authors had no relevant disclosures.

SOURCE: Bray TJP et al. Rheumatology 2019;58(suppl 3): Abstract 033. doi: 10.1093/rheumatology/kez105.032.

BIRMINGHAM, ENGLAND – Higher blood biologic drug levels in the first year of treatment for rheumatoid arthritis independently increased the risk of any infection by about 50% when compared against low or normal levels in a new observational cohort study, providing support for monitoring biologic drug levels to help to predict infection risk.

Data from the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis (BSRBR-RA) that were presented at the British Society for Rheumatology annual conference showed that the adjusted hazard ratio for any infection occurring within the first year among patients with high drug levels was 1.51, with a 95% confidence interval (CI) of 1.14 to 2.01. The adjustments took into account patients’ age, gender, disease activity score, and use of methotrexate.

There are more than 10 biologics now available for use in rheumatoid arthritis but deciding which to use in a particular patient remains very much “a trial and error approach,” first author Meghna Jani, MBChB, said at the conference.

Sara Freeman/MDedge News

“From a patient perspective, one of the most important concerns continues to be the risk of serious infections and adverse events,” added Dr. Jani, a National Institute for Health Research Academic Clinical Lecturer in Rheumatology at the University of Manchester (England).

The link between biologic agents and infections, including those that could result in hospitalization or other serious consequences, has been well studied in biologics registries. It is known, for example, that the risk of infections with tumor necrosis factor inhibitor treatment seems to be highest during the first 6-12 months of treatment.

According to Dr. Jani, conventional means of determining risk – such as patient age and the presence of comorbid factors – have limited benefit in terms of deciding which patients could be at heightened risk of infections. “Ideally, we need biomarkers in rheumatology that can be implemented in clinical practice and help us predict efficacy and safety, as well as help us use these medications much more cost-effectively,” she said.

Four years ago, a meta-analysis (Lancet. 2015;386:258-65) suggested that the risk of infection may be linked to using higher doses of anti–tumor necrosis factor drugs, which led the BSRBR-RA team to see if elevated levels of these drugs in the serum could be predictive of the infection risk and thus used as a possible biomarker. There was also prior evidence that serum drug concentrations of biologics were associated with long-term treatment response and that a certain level was needed to determine the likely treatment response.

In the current study, Dr. Jani and colleagues used data on 703 patients with rheumatoid arthritis starting biologic therapy who were simultaneously recruited into the BSRBR-RA, which has been running since 2001, and the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS). The BSRBR-RA did not collect biological samples, but in BRAGGSS serological samples were collected at 3-, 6-, and 12-month intervals after the start of a biologic treatment, along with other assessments. This is the first time two national, U.K.-based, rheumatoid arthritis cohorts have been linked in this way, Dr. Jani said.

Serum samples taken from the patients were assessed via enzyme-linked immunoassay to determine levels of the biologic agent used, with high drug levels defined as more than 4 mcg/mL for etanercept (n = 286), tocilizumab (n = 104), and infliximab (n = 14); more than 8 mcg/mL for adalimumab (n = 179), and 25 mcg/mL or more for certolizumab pegol (n = 120).

In the study, about three-quarters of the patients were women. The mean age was 58 years, and disease duration was just under 6 years. Most patients were starting their first biologic.

The crude rate of all infections at 1 year, including recurrent infections, was 464 per 1,000 patient-years in the high biologic drug level group versus 314 per 1,000 patient-years in the low biologic drug level group. When only the first infections were considered, the crude rate of all infections within the first year were a respective 300 and 229 per 1,000 patient-years, with an adjusted hazard ratio of 1.27, Dr. Jani reported.

As expected, lower respiratory tract infections were the most common type of infection, occurring in 34% of patients with high drug levels versus around 10% in the low drug level group. Upper respiratory tract, urinary tract, and skin infections including shingles were seen in a respective 16%, 15%, and 8% in the high drug level group, with rates less than 5% in the low drug level group.

Of note, there were certain types of infections present in the high but not low drug level groups: bacterial peritonitis, neutropenic sepsis, and herpes zoster.

Crude rates for serious infections at 1 year were 76 and 54 per 1,000 patient-years, respectively, for the high and low drug level groups. The crude rates for the first serious infection within the first year were 44 and 29 per 1,000 patient-years. The adjusted hazard ratio for the risk of serious infection at 1 year was 1.26. Serious infections were rare events, Dr. Jani emphasized, so the power was reduced, but “there was a slightly increased risk.”

Aside from the low statistical power to assess the rarer serious infections, another limitation was that drug levels were not measured at the time of the adverse event.

Concluding, Dr. Jani suggested that perhaps monitoring drug levels could be useful in predicting the risk of infection in patients being treated with biologics for rheumatoid arthritis.

Furthermore, “in patients with remission, dose-tapering guided by therapeutic drug monitoring may help lower infection risk and help us balance safety and efficacy.”

When asked to comment, Tore K. Kvien, MD, PhD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, supported this conclusion. “Therapeutic drug monitoring [TDM] is widely used among gastroenterologists when treating inflammatory bowel diseases with TNF inhibitors. In recent years, data from several research groups in rheumatology have indicated that TDM may help to optimize drug efficacy. The results from Dr. Jani and her colleagues also support that TDM may be important for safety. The importance of TDM as a ‘new’ hot topic in rheumatology is also supported by the recent establishment of a EULAR [European League Against Rheumatism] task force to further explore the value of TDM when treating patients with inflammatory joint diseases.”

The BSRBR-RA is funded through the BSR, which receives restricted income from several U.K. pharmaceutical companies. These currently include AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche, and in the past, Swedish Orphan Biovitrum and Merck. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Jani has no personal conflicts of interest to disclose.
 

SOURCE: Jani M et al. Rheumatology, 2019 April;58(Suppl 3):kez105.018.

BIRMINGHAM, ENGLAND – Higher blood biologic drug levels in the first year of treatment for rheumatoid arthritis independently increased the risk of any infection by about 50% when compared against low or normal levels in a new observational cohort study, providing support for monitoring biologic drug levels to help to predict infection risk.

Data from the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis (BSRBR-RA) that were presented at the British Society for Rheumatology annual conference showed that the adjusted hazard ratio for any infection occurring within the first year among patients with high drug levels was 1.51, with a 95% confidence interval (CI) of 1.14 to 2.01. The adjustments took into account patients’ age, gender, disease activity score, and use of methotrexate.

There are more than 10 biologics now available for use in rheumatoid arthritis but deciding which to use in a particular patient remains very much “a trial and error approach,” first author Meghna Jani, MBChB, said at the conference.

Sara Freeman/MDedge News

“From a patient perspective, one of the most important concerns continues to be the risk of serious infections and adverse events,” added Dr. Jani, a National Institute for Health Research Academic Clinical Lecturer in Rheumatology at the University of Manchester (England).

The link between biologic agents and infections, including those that could result in hospitalization or other serious consequences, has been well studied in biologics registries. It is known, for example, that the risk of infections with tumor necrosis factor inhibitor treatment seems to be highest during the first 6-12 months of treatment.

According to Dr. Jani, conventional means of determining risk – such as patient age and the presence of comorbid factors – have limited benefit in terms of deciding which patients could be at heightened risk of infections. “Ideally, we need biomarkers in rheumatology that can be implemented in clinical practice and help us predict efficacy and safety, as well as help us use these medications much more cost-effectively,” she said.

Four years ago, a meta-analysis (Lancet. 2015;386:258-65) suggested that the risk of infection may be linked to using higher doses of anti–tumor necrosis factor drugs, which led the BSRBR-RA team to see if elevated levels of these drugs in the serum could be predictive of the infection risk and thus used as a possible biomarker. There was also prior evidence that serum drug concentrations of biologics were associated with long-term treatment response and that a certain level was needed to determine the likely treatment response.

In the current study, Dr. Jani and colleagues used data on 703 patients with rheumatoid arthritis starting biologic therapy who were simultaneously recruited into the BSRBR-RA, which has been running since 2001, and the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS). The BSRBR-RA did not collect biological samples, but in BRAGGSS serological samples were collected at 3-, 6-, and 12-month intervals after the start of a biologic treatment, along with other assessments. This is the first time two national, U.K.-based, rheumatoid arthritis cohorts have been linked in this way, Dr. Jani said.

Serum samples taken from the patients were assessed via enzyme-linked immunoassay to determine levels of the biologic agent used, with high drug levels defined as more than 4 mcg/mL for etanercept (n = 286), tocilizumab (n = 104), and infliximab (n = 14); more than 8 mcg/mL for adalimumab (n = 179), and 25 mcg/mL or more for certolizumab pegol (n = 120).

In the study, about three-quarters of the patients were women. The mean age was 58 years, and disease duration was just under 6 years. Most patients were starting their first biologic.

The crude rate of all infections at 1 year, including recurrent infections, was 464 per 1,000 patient-years in the high biologic drug level group versus 314 per 1,000 patient-years in the low biologic drug level group. When only the first infections were considered, the crude rate of all infections within the first year were a respective 300 and 229 per 1,000 patient-years, with an adjusted hazard ratio of 1.27, Dr. Jani reported.

As expected, lower respiratory tract infections were the most common type of infection, occurring in 34% of patients with high drug levels versus around 10% in the low drug level group. Upper respiratory tract, urinary tract, and skin infections including shingles were seen in a respective 16%, 15%, and 8% in the high drug level group, with rates less than 5% in the low drug level group.

Of note, there were certain types of infections present in the high but not low drug level groups: bacterial peritonitis, neutropenic sepsis, and herpes zoster.

Crude rates for serious infections at 1 year were 76 and 54 per 1,000 patient-years, respectively, for the high and low drug level groups. The crude rates for the first serious infection within the first year were 44 and 29 per 1,000 patient-years. The adjusted hazard ratio for the risk of serious infection at 1 year was 1.26. Serious infections were rare events, Dr. Jani emphasized, so the power was reduced, but “there was a slightly increased risk.”

Aside from the low statistical power to assess the rarer serious infections, another limitation was that drug levels were not measured at the time of the adverse event.

Concluding, Dr. Jani suggested that perhaps monitoring drug levels could be useful in predicting the risk of infection in patients being treated with biologics for rheumatoid arthritis.

Furthermore, “in patients with remission, dose-tapering guided by therapeutic drug monitoring may help lower infection risk and help us balance safety and efficacy.”

When asked to comment, Tore K. Kvien, MD, PhD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, supported this conclusion. “Therapeutic drug monitoring [TDM] is widely used among gastroenterologists when treating inflammatory bowel diseases with TNF inhibitors. In recent years, data from several research groups in rheumatology have indicated that TDM may help to optimize drug efficacy. The results from Dr. Jani and her colleagues also support that TDM may be important for safety. The importance of TDM as a ‘new’ hot topic in rheumatology is also supported by the recent establishment of a EULAR [European League Against Rheumatism] task force to further explore the value of TDM when treating patients with inflammatory joint diseases.”

The BSRBR-RA is funded through the BSR, which receives restricted income from several U.K. pharmaceutical companies. These currently include AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche, and in the past, Swedish Orphan Biovitrum and Merck. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Jani has no personal conflicts of interest to disclose.
 

SOURCE: Jani M et al. Rheumatology, 2019 April;58(Suppl 3):kez105.018.

BIRMINGHAM, ENGLAND – Higher blood biologic drug levels in the first year of treatment for rheumatoid arthritis independently increased the risk of any infection by about 50% when compared against low or normal levels in a new observational cohort study, providing support for monitoring biologic drug levels to help to predict infection risk.

Data from the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis (BSRBR-RA) that were presented at the British Society for Rheumatology annual conference showed that the adjusted hazard ratio for any infection occurring within the first year among patients with high drug levels was 1.51, with a 95% confidence interval (CI) of 1.14 to 2.01. The adjustments took into account patients’ age, gender, disease activity score, and use of methotrexate.

There are more than 10 biologics now available for use in rheumatoid arthritis but deciding which to use in a particular patient remains very much “a trial and error approach,” first author Meghna Jani, MBChB, said at the conference.

Sara Freeman/MDedge News

“From a patient perspective, one of the most important concerns continues to be the risk of serious infections and adverse events,” added Dr. Jani, a National Institute for Health Research Academic Clinical Lecturer in Rheumatology at the University of Manchester (England).

The link between biologic agents and infections, including those that could result in hospitalization or other serious consequences, has been well studied in biologics registries. It is known, for example, that the risk of infections with tumor necrosis factor inhibitor treatment seems to be highest during the first 6-12 months of treatment.

According to Dr. Jani, conventional means of determining risk – such as patient age and the presence of comorbid factors – have limited benefit in terms of deciding which patients could be at heightened risk of infections. “Ideally, we need biomarkers in rheumatology that can be implemented in clinical practice and help us predict efficacy and safety, as well as help us use these medications much more cost-effectively,” she said.

Four years ago, a meta-analysis (Lancet. 2015;386:258-65) suggested that the risk of infection may be linked to using higher doses of anti–tumor necrosis factor drugs, which led the BSRBR-RA team to see if elevated levels of these drugs in the serum could be predictive of the infection risk and thus used as a possible biomarker. There was also prior evidence that serum drug concentrations of biologics were associated with long-term treatment response and that a certain level was needed to determine the likely treatment response.

In the current study, Dr. Jani and colleagues used data on 703 patients with rheumatoid arthritis starting biologic therapy who were simultaneously recruited into the BSRBR-RA, which has been running since 2001, and the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS). The BSRBR-RA did not collect biological samples, but in BRAGGSS serological samples were collected at 3-, 6-, and 12-month intervals after the start of a biologic treatment, along with other assessments. This is the first time two national, U.K.-based, rheumatoid arthritis cohorts have been linked in this way, Dr. Jani said.

Serum samples taken from the patients were assessed via enzyme-linked immunoassay to determine levels of the biologic agent used, with high drug levels defined as more than 4 mcg/mL for etanercept (n = 286), tocilizumab (n = 104), and infliximab (n = 14); more than 8 mcg/mL for adalimumab (n = 179), and 25 mcg/mL or more for certolizumab pegol (n = 120).

In the study, about three-quarters of the patients were women. The mean age was 58 years, and disease duration was just under 6 years. Most patients were starting their first biologic.

The crude rate of all infections at 1 year, including recurrent infections, was 464 per 1,000 patient-years in the high biologic drug level group versus 314 per 1,000 patient-years in the low biologic drug level group. When only the first infections were considered, the crude rate of all infections within the first year were a respective 300 and 229 per 1,000 patient-years, with an adjusted hazard ratio of 1.27, Dr. Jani reported.

As expected, lower respiratory tract infections were the most common type of infection, occurring in 34% of patients with high drug levels versus around 10% in the low drug level group. Upper respiratory tract, urinary tract, and skin infections including shingles were seen in a respective 16%, 15%, and 8% in the high drug level group, with rates less than 5% in the low drug level group.

Of note, there were certain types of infections present in the high but not low drug level groups: bacterial peritonitis, neutropenic sepsis, and herpes zoster.

Crude rates for serious infections at 1 year were 76 and 54 per 1,000 patient-years, respectively, for the high and low drug level groups. The crude rates for the first serious infection within the first year were 44 and 29 per 1,000 patient-years. The adjusted hazard ratio for the risk of serious infection at 1 year was 1.26. Serious infections were rare events, Dr. Jani emphasized, so the power was reduced, but “there was a slightly increased risk.”

Aside from the low statistical power to assess the rarer serious infections, another limitation was that drug levels were not measured at the time of the adverse event.

Concluding, Dr. Jani suggested that perhaps monitoring drug levels could be useful in predicting the risk of infection in patients being treated with biologics for rheumatoid arthritis.

Furthermore, “in patients with remission, dose-tapering guided by therapeutic drug monitoring may help lower infection risk and help us balance safety and efficacy.”

When asked to comment, Tore K. Kvien, MD, PhD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, supported this conclusion. “Therapeutic drug monitoring [TDM] is widely used among gastroenterologists when treating inflammatory bowel diseases with TNF inhibitors. In recent years, data from several research groups in rheumatology have indicated that TDM may help to optimize drug efficacy. The results from Dr. Jani and her colleagues also support that TDM may be important for safety. The importance of TDM as a ‘new’ hot topic in rheumatology is also supported by the recent establishment of a EULAR [European League Against Rheumatism] task force to further explore the value of TDM when treating patients with inflammatory joint diseases.”

The BSRBR-RA is funded through the BSR, which receives restricted income from several U.K. pharmaceutical companies. These currently include AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche, and in the past, Swedish Orphan Biovitrum and Merck. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Jani has no personal conflicts of interest to disclose.
 

SOURCE: Jani M et al. Rheumatology, 2019 April;58(Suppl 3):kez105.018.