Ankylosing spondylitis

LONDON – The option of treating axial spondyloarthritis with an interleukin-17 inhibitor has become an officially recommended option for the first time in a new update to management recommendations for this disease released by a task force assembled jointly by the Assessment of SpondyloArthritis International Society and the European League Against Rheumatism.

The update replaces recommendations last released by the two groups for managing patients with ankylosing spondylitis in 2010 (Ann Rheum Dis. 2011 June;70[6]:896-904), as well as the prior recommendations from the two organizations for using tumor necrosis factor (TNF) inhibitors on these patients (Ann Rheum Dis. 2011 June;70[6]:905-8). The new update also broadens the disease spectrum from ankylosing spondylitis to axial spondyloarthritis (SpA).

Mitchel L. Zoler/Frontline Medical News

The latest recommendations continue to place nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line pharmacotherapy for patients with axial SpA to control pain and stiffness, and continue to place treatment with a biological disease modifying antirheumatic drug (DMARD) – identified in the recommendations as most typically a TNF inhibitor by current practice – as second-line treatment after NSAIDs. The recommendations specify that initiation of a biological DMARD should target patients who have both failed treatment with at least two different NSAIDs over the course of at least 4 weeks of treatment, and who have active disease documented by either of two standard measures of disease activity in patients with axial SpA: either a score of at least 2.1 on the ankylosing spondylitis disease activity score (ASDAS) or a score of at least 4 on the Bath ankylosing spondylitis disease activity index (BASDAI).

Incorporation of the ASDAS as a potential alternative to the BASDAI for assessing disease activity in these patients is another new feature of these recommendations, noted Dr. Désirée van der Heijde, convenor of the update task force, who presented the new recommendations at the European Congress of Rheumatology.

The new recommendations place use of an interleukin (IL)-17 inhibitor as a third-line management option, for patients who fail to adequately respond to a first TNF inhibitor, and they also say that an alternative to starting an IL-17 inhibitor at this stage of management is to instead try treatment with a second type of TNF inhibitor. The IL-17 inhibitor class includes secukinumab (Cosentyx), which received approval from the Food and Drug Administration for treating active ankylosing spondylitis in January 2016, and which also has approval for the same indication from the European Medicines Agency.

The updated recommendations leave unchanged from the prior version advice to use biological DMARDs only after failure of other treatments, as well as advocacy of nondrug therapy with regular exercise, smoking cessation, and physical therapy when appropriate as the very first therapeutic step to take, before even starting a NSAID regimen. For patients with axial SpA who have peripheral arthritis, the recommendations say that clinicians can consider treatment with a local injection of a glucocorticoid, and a treatment course with sulfasalazine. The recommendations do not endorse treatment with a conventional, synthetic DMARD for patients with purely axial disease, and they also recommend against long-term treatment with a systemic corticosteroid. The update calls analgesics contraindicated.

Another new feature of the updated recommendations is endorsement of treating axial SpA patients to a predefined treatment target, although the recommendations left the nature of that target undefined and is something for the treating clinician to discuss and tailor to each patient individually, said Dr. van der Heijde, professor of rheumatology at Leiden University Medical Center in The Netherlands. The update also introduces for the first time the recommendation to consider tapering down treatment with a biological DMARD for patients who achieve remission.

Dr. van der Heijde said that she has been a consultant to 17 drug companies.

[email protected]

On Twitter @mitchelzoler

LONDON – The option of treating axial spondyloarthritis with an interleukin-17 inhibitor has become an officially recommended option for the first time in a new update to management recommendations for this disease released by a task force assembled jointly by the Assessment of SpondyloArthritis International Society and the European League Against Rheumatism.

The update replaces recommendations last released by the two groups for managing patients with ankylosing spondylitis in 2010 (Ann Rheum Dis. 2011 June;70[6]:896-904), as well as the prior recommendations from the two organizations for using tumor necrosis factor (TNF) inhibitors on these patients (Ann Rheum Dis. 2011 June;70[6]:905-8). The new update also broadens the disease spectrum from ankylosing spondylitis to axial spondyloarthritis (SpA).

Mitchel L. Zoler/Frontline Medical News

The latest recommendations continue to place nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line pharmacotherapy for patients with axial SpA to control pain and stiffness, and continue to place treatment with a biological disease modifying antirheumatic drug (DMARD) – identified in the recommendations as most typically a TNF inhibitor by current practice – as second-line treatment after NSAIDs. The recommendations specify that initiation of a biological DMARD should target patients who have both failed treatment with at least two different NSAIDs over the course of at least 4 weeks of treatment, and who have active disease documented by either of two standard measures of disease activity in patients with axial SpA: either a score of at least 2.1 on the ankylosing spondylitis disease activity score (ASDAS) or a score of at least 4 on the Bath ankylosing spondylitis disease activity index (BASDAI).

Incorporation of the ASDAS as a potential alternative to the BASDAI for assessing disease activity in these patients is another new feature of these recommendations, noted Dr. Désirée van der Heijde, convenor of the update task force, who presented the new recommendations at the European Congress of Rheumatology.

The new recommendations place use of an interleukin (IL)-17 inhibitor as a third-line management option, for patients who fail to adequately respond to a first TNF inhibitor, and they also say that an alternative to starting an IL-17 inhibitor at this stage of management is to instead try treatment with a second type of TNF inhibitor. The IL-17 inhibitor class includes secukinumab (Cosentyx), which received approval from the Food and Drug Administration for treating active ankylosing spondylitis in January 2016, and which also has approval for the same indication from the European Medicines Agency.

The updated recommendations leave unchanged from the prior version advice to use biological DMARDs only after failure of other treatments, as well as advocacy of nondrug therapy with regular exercise, smoking cessation, and physical therapy when appropriate as the very first therapeutic step to take, before even starting a NSAID regimen. For patients with axial SpA who have peripheral arthritis, the recommendations say that clinicians can consider treatment with a local injection of a glucocorticoid, and a treatment course with sulfasalazine. The recommendations do not endorse treatment with a conventional, synthetic DMARD for patients with purely axial disease, and they also recommend against long-term treatment with a systemic corticosteroid. The update calls analgesics contraindicated.

Another new feature of the updated recommendations is endorsement of treating axial SpA patients to a predefined treatment target, although the recommendations left the nature of that target undefined and is something for the treating clinician to discuss and tailor to each patient individually, said Dr. van der Heijde, professor of rheumatology at Leiden University Medical Center in The Netherlands. The update also introduces for the first time the recommendation to consider tapering down treatment with a biological DMARD for patients who achieve remission.

Dr. van der Heijde said that she has been a consultant to 17 drug companies.

[email protected]

On Twitter @mitchelzoler

LONDON – The option of treating axial spondyloarthritis with an interleukin-17 inhibitor has become an officially recommended option for the first time in a new update to management recommendations for this disease released by a task force assembled jointly by the Assessment of SpondyloArthritis International Society and the European League Against Rheumatism.

The update replaces recommendations last released by the two groups for managing patients with ankylosing spondylitis in 2010 (Ann Rheum Dis. 2011 June;70[6]:896-904), as well as the prior recommendations from the two organizations for using tumor necrosis factor (TNF) inhibitors on these patients (Ann Rheum Dis. 2011 June;70[6]:905-8). The new update also broadens the disease spectrum from ankylosing spondylitis to axial spondyloarthritis (SpA).

Mitchel L. Zoler/Frontline Medical News

The latest recommendations continue to place nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line pharmacotherapy for patients with axial SpA to control pain and stiffness, and continue to place treatment with a biological disease modifying antirheumatic drug (DMARD) – identified in the recommendations as most typically a TNF inhibitor by current practice – as second-line treatment after NSAIDs. The recommendations specify that initiation of a biological DMARD should target patients who have both failed treatment with at least two different NSAIDs over the course of at least 4 weeks of treatment, and who have active disease documented by either of two standard measures of disease activity in patients with axial SpA: either a score of at least 2.1 on the ankylosing spondylitis disease activity score (ASDAS) or a score of at least 4 on the Bath ankylosing spondylitis disease activity index (BASDAI).

Incorporation of the ASDAS as a potential alternative to the BASDAI for assessing disease activity in these patients is another new feature of these recommendations, noted Dr. Désirée van der Heijde, convenor of the update task force, who presented the new recommendations at the European Congress of Rheumatology.

The new recommendations place use of an interleukin (IL)-17 inhibitor as a third-line management option, for patients who fail to adequately respond to a first TNF inhibitor, and they also say that an alternative to starting an IL-17 inhibitor at this stage of management is to instead try treatment with a second type of TNF inhibitor. The IL-17 inhibitor class includes secukinumab (Cosentyx), which received approval from the Food and Drug Administration for treating active ankylosing spondylitis in January 2016, and which also has approval for the same indication from the European Medicines Agency.

The updated recommendations leave unchanged from the prior version advice to use biological DMARDs only after failure of other treatments, as well as advocacy of nondrug therapy with regular exercise, smoking cessation, and physical therapy when appropriate as the very first therapeutic step to take, before even starting a NSAID regimen. For patients with axial SpA who have peripheral arthritis, the recommendations say that clinicians can consider treatment with a local injection of a glucocorticoid, and a treatment course with sulfasalazine. The recommendations do not endorse treatment with a conventional, synthetic DMARD for patients with purely axial disease, and they also recommend against long-term treatment with a systemic corticosteroid. The update calls analgesics contraindicated.

Another new feature of the updated recommendations is endorsement of treating axial SpA patients to a predefined treatment target, although the recommendations left the nature of that target undefined and is something for the treating clinician to discuss and tailor to each patient individually, said Dr. van der Heijde, professor of rheumatology at Leiden University Medical Center in The Netherlands. The update also introduces for the first time the recommendation to consider tapering down treatment with a biological DMARD for patients who achieve remission.

Dr. van der Heijde said that she has been a consultant to 17 drug companies.

[email protected]

On Twitter @mitchelzoler

LONDON – Long-term treatment with the interleukin 17A inhibitor secukinumab showed suggestive evidence of inhibiting structural progression of spinal disease in 168 patients with ankylosing spondylitis, the first time any evidence for an effect like this has been seen with a biologic drug or any other agent used to treat ankylosing spondylitis.

However, the effect occurred in uncontrolled, 2-year open-label treatment of patients originally enrolled in one of the secukinumab pivotal trials, and the analysis did not include comparison against a historical control group, caveats that demand confirmation of this effect in additional studies, Dr. Jürgen Braun said at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

In a second, unrelated study, the oral Janus kinase inhibitor tofacitinib showed promising efficacy for controlling clinical symptoms in patients with active ankylosing spondylitis (AS) during 12 weeks of treatment in a placebo-controlled, dose-ranging phase II study.

The open-label secukinumab extension study involved patients who had been enrolled in the MEASURE 1 study, one of the pivotal trials that had established secukinumab as safe and effective for improving the clinical status of patients with active AS. The primary endpoint of MEASURE 1 had been the percentage of patients achieving at least a 20% improvement in their Assessment of Spondyloarthritis international Society (ASAS20) response after 16 weeks of treatment (New Engl J Med. 2015 Dec 24;373[26]:2534-48).

Based in part on these data the Food and Drug Administration approved secukinumab (Cosentyx) for the treatment of ankylosing spondylitis in January 2016. The new data reported by Dr. Braun assessed the level of spinal pathology in a subgroup of the MEASURE 1 patients when measured by radiography using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) at baseline and after 104 weeks on secukinumab treatment.

Patients in MEASURE 1 who began on active treatment received 10 mg/kg intravenous secukinumab for 4 weeks, followed by subcutaneous dosages of either 75 mg or 150 mg every 4 weeks for 104 weeks. His analysis also included some patients who entered MEASURE 1 in the placebo group and then switched to open-label, subcutaneous secukinumab treatment after 16 or 24 weeks on placebo.

Analysis of 168 patients who started on intravenous secukinumab and later received any subcutaneous secukinumab treatment out to 104 weeks showed an average increase in mSASSS of 0.30 after 104 weeks when compared against their baseline scores, reported Dr. Braun, professor and medical director of the Ruhr Rheumatology Center of the University of Bochum, Germany.

Among an additional 89 patients who began in the placebo group and then switched to subcutaneous secukinumab, the average change in mSASSS from baseline to 104 weeks was 0.54. By comparison, Dr. Braun noted that AS patients treated with a tumor necrosis factor inhibitor have shown 2-year progression in their mSASSS of about 0.8-0.9, and AS patients not treated with an active biologic drug have shown 2-year mSASSS progression of about 1.0.

A second analysis of the data reported by Dr. Braun showed that among the 168 patients treated for the full 104 weeks with secukinumab about 80% showed no mSASSS progression, but about 20% did have some level of detectable mSASSS progression.

The phase II study of tofacitinib (Xeljanz) randomized 208 patients with active AS to either tofacitinib at daily dosages of 2 mg bid, 5 mg bid, 10 mg bid, or placebo. The study’s primary endpoint was their ASAS20 response after 12 weeks that underwent a Bayesian Emax model analysis to estimate incremental efficacy when compared against placebo.

The primary efficacy analysis showed the greatest EmaxASAS20 response among patients treated with 5 mg bid daily, 63%, which was about 23% above the placebo level, reportedDr. Désirée van der Heijde, professor of rheumatology at the Leiden University Medical Center, The Netherlands. The absolute ASAS20 response rate of the 52 patients randomized to this tofacitinib dosage was about 81%, about 40% higher than the response rate seen in the 51 patients in the placebo arm.

All dosages of tofacitinib tested were well tolerated, with safety data similar to what has previously been shown for tofacitinib, a drug that has Food and Drug Administration approval for treating rheumatoid arthritis.

[email protected]

On Twitter @mitchelzoler

LONDON – Long-term treatment with the interleukin 17A inhibitor secukinumab showed suggestive evidence of inhibiting structural progression of spinal disease in 168 patients with ankylosing spondylitis, the first time any evidence for an effect like this has been seen with a biologic drug or any other agent used to treat ankylosing spondylitis.

However, the effect occurred in uncontrolled, 2-year open-label treatment of patients originally enrolled in one of the secukinumab pivotal trials, and the analysis did not include comparison against a historical control group, caveats that demand confirmation of this effect in additional studies, Dr. Jürgen Braun said at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

In a second, unrelated study, the oral Janus kinase inhibitor tofacitinib showed promising efficacy for controlling clinical symptoms in patients with active ankylosing spondylitis (AS) during 12 weeks of treatment in a placebo-controlled, dose-ranging phase II study.

The open-label secukinumab extension study involved patients who had been enrolled in the MEASURE 1 study, one of the pivotal trials that had established secukinumab as safe and effective for improving the clinical status of patients with active AS. The primary endpoint of MEASURE 1 had been the percentage of patients achieving at least a 20% improvement in their Assessment of Spondyloarthritis international Society (ASAS20) response after 16 weeks of treatment (New Engl J Med. 2015 Dec 24;373[26]:2534-48).

Based in part on these data the Food and Drug Administration approved secukinumab (Cosentyx) for the treatment of ankylosing spondylitis in January 2016. The new data reported by Dr. Braun assessed the level of spinal pathology in a subgroup of the MEASURE 1 patients when measured by radiography using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) at baseline and after 104 weeks on secukinumab treatment.

Patients in MEASURE 1 who began on active treatment received 10 mg/kg intravenous secukinumab for 4 weeks, followed by subcutaneous dosages of either 75 mg or 150 mg every 4 weeks for 104 weeks. His analysis also included some patients who entered MEASURE 1 in the placebo group and then switched to open-label, subcutaneous secukinumab treatment after 16 or 24 weeks on placebo.

Analysis of 168 patients who started on intravenous secukinumab and later received any subcutaneous secukinumab treatment out to 104 weeks showed an average increase in mSASSS of 0.30 after 104 weeks when compared against their baseline scores, reported Dr. Braun, professor and medical director of the Ruhr Rheumatology Center of the University of Bochum, Germany.

Among an additional 89 patients who began in the placebo group and then switched to subcutaneous secukinumab, the average change in mSASSS from baseline to 104 weeks was 0.54. By comparison, Dr. Braun noted that AS patients treated with a tumor necrosis factor inhibitor have shown 2-year progression in their mSASSS of about 0.8-0.9, and AS patients not treated with an active biologic drug have shown 2-year mSASSS progression of about 1.0.

A second analysis of the data reported by Dr. Braun showed that among the 168 patients treated for the full 104 weeks with secukinumab about 80% showed no mSASSS progression, but about 20% did have some level of detectable mSASSS progression.

The phase II study of tofacitinib (Xeljanz) randomized 208 patients with active AS to either tofacitinib at daily dosages of 2 mg bid, 5 mg bid, 10 mg bid, or placebo. The study’s primary endpoint was their ASAS20 response after 12 weeks that underwent a Bayesian Emax model analysis to estimate incremental efficacy when compared against placebo.

The primary efficacy analysis showed the greatest EmaxASAS20 response among patients treated with 5 mg bid daily, 63%, which was about 23% above the placebo level, reportedDr. Désirée van der Heijde, professor of rheumatology at the Leiden University Medical Center, The Netherlands. The absolute ASAS20 response rate of the 52 patients randomized to this tofacitinib dosage was about 81%, about 40% higher than the response rate seen in the 51 patients in the placebo arm.

All dosages of tofacitinib tested were well tolerated, with safety data similar to what has previously been shown for tofacitinib, a drug that has Food and Drug Administration approval for treating rheumatoid arthritis.

[email protected]

On Twitter @mitchelzoler

LONDON – Long-term treatment with the interleukin 17A inhibitor secukinumab showed suggestive evidence of inhibiting structural progression of spinal disease in 168 patients with ankylosing spondylitis, the first time any evidence for an effect like this has been seen with a biologic drug or any other agent used to treat ankylosing spondylitis.

However, the effect occurred in uncontrolled, 2-year open-label treatment of patients originally enrolled in one of the secukinumab pivotal trials, and the analysis did not include comparison against a historical control group, caveats that demand confirmation of this effect in additional studies, Dr. Jürgen Braun said at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

In a second, unrelated study, the oral Janus kinase inhibitor tofacitinib showed promising efficacy for controlling clinical symptoms in patients with active ankylosing spondylitis (AS) during 12 weeks of treatment in a placebo-controlled, dose-ranging phase II study.

The open-label secukinumab extension study involved patients who had been enrolled in the MEASURE 1 study, one of the pivotal trials that had established secukinumab as safe and effective for improving the clinical status of patients with active AS. The primary endpoint of MEASURE 1 had been the percentage of patients achieving at least a 20% improvement in their Assessment of Spondyloarthritis international Society (ASAS20) response after 16 weeks of treatment (New Engl J Med. 2015 Dec 24;373[26]:2534-48).

Based in part on these data the Food and Drug Administration approved secukinumab (Cosentyx) for the treatment of ankylosing spondylitis in January 2016. The new data reported by Dr. Braun assessed the level of spinal pathology in a subgroup of the MEASURE 1 patients when measured by radiography using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) at baseline and after 104 weeks on secukinumab treatment.

Patients in MEASURE 1 who began on active treatment received 10 mg/kg intravenous secukinumab for 4 weeks, followed by subcutaneous dosages of either 75 mg or 150 mg every 4 weeks for 104 weeks. His analysis also included some patients who entered MEASURE 1 in the placebo group and then switched to open-label, subcutaneous secukinumab treatment after 16 or 24 weeks on placebo.

Analysis of 168 patients who started on intravenous secukinumab and later received any subcutaneous secukinumab treatment out to 104 weeks showed an average increase in mSASSS of 0.30 after 104 weeks when compared against their baseline scores, reported Dr. Braun, professor and medical director of the Ruhr Rheumatology Center of the University of Bochum, Germany.

Among an additional 89 patients who began in the placebo group and then switched to subcutaneous secukinumab, the average change in mSASSS from baseline to 104 weeks was 0.54. By comparison, Dr. Braun noted that AS patients treated with a tumor necrosis factor inhibitor have shown 2-year progression in their mSASSS of about 0.8-0.9, and AS patients not treated with an active biologic drug have shown 2-year mSASSS progression of about 1.0.

A second analysis of the data reported by Dr. Braun showed that among the 168 patients treated for the full 104 weeks with secukinumab about 80% showed no mSASSS progression, but about 20% did have some level of detectable mSASSS progression.

The phase II study of tofacitinib (Xeljanz) randomized 208 patients with active AS to either tofacitinib at daily dosages of 2 mg bid, 5 mg bid, 10 mg bid, or placebo. The study’s primary endpoint was their ASAS20 response after 12 weeks that underwent a Bayesian Emax model analysis to estimate incremental efficacy when compared against placebo.

The primary efficacy analysis showed the greatest EmaxASAS20 response among patients treated with 5 mg bid daily, 63%, which was about 23% above the placebo level, reportedDr. Désirée van der Heijde, professor of rheumatology at the Leiden University Medical Center, The Netherlands. The absolute ASAS20 response rate of the 52 patients randomized to this tofacitinib dosage was about 81%, about 40% higher than the response rate seen in the 51 patients in the placebo arm.

All dosages of tofacitinib tested were well tolerated, with safety data similar to what has previously been shown for tofacitinib, a drug that has Food and Drug Administration approval for treating rheumatoid arthritis.

[email protected]

On Twitter @mitchelzoler

As many as one-third of healthy first-degree relatives of individuals with ankylosing spondylitis may meet the criteria for spondyloarthritis, according to results from a prospective cohort study.

Dr. Maureen C. Turina of the Amsterdam Rheumatology and Immunology Center at the University of Amsterdam and her coauthors enrolled 51 first-degree relatives of individuals with HLA-B27–positive ankylosing spondylitis in the study to see whether any of these otherwise healthy individuals showed early signs of the disease. They found that 17 (33%) of these first-degree relatives fulfilled any of the spondyloarthritis (SpA) classification criteria at baseline – a higher rate than reported in previous studies – and 7 (14%) met both the Assessment of Spondyloarthritis International Society (ASAS) criteria and European Spondyloarthropathy Study Group (ESSG) criteria.

©Rocky89/Thinkstock.com

The authors suggested that the higher rate, compared with previous studies, could be due to channeling bias, as individuals with clinical symptoms may have been more willing to participate in the study.

However, 4 of the 38 individuals who did not fulfill either of these criteria for SpA still showed imaging abnormalities – including syndesmophytes on the cervical spine and bone marrow edema in the sacroiliac joint.

The authors suggested these imaging abnormalities may represent a subclinical phase of SpA (Arthritis Rheumatol. 2016 May 23. doi: 10.1002/art.39766).

The participants who met the ASAS and/or ESSG classification criteria for SpA had more axial, entheseal, and joint pain, compared with those who did not meet the criteria. All of these patients also reported back pain, compared with 35% of those who did not fulfill the criteria.

However, the individuals meeting the SpA criteria had low overall disease scores, and did not show any increase in inflammatory serum markers.

“Importantly, some key features of SpA including the presence of peripheral disease or extra-articular manifestations and increased inflammatory parameters were only rarely observed in FDRs [first-degree relatives] and were also not different in those fulfilling the ASAS axSpA and/or ESSG classification criteria versus those who did not,” the authors reported.

“Future follow-up will learn if and which of these FDRs will evolve into the clinically established phase of SpA.”

When specifically asked, more than half (57%) of the first-degree relatives said they had back pain, and 40% said they had experienced or were experiencing arthralgia.

“The fact that these FDRs were not investigated for or diagnosed with axial SpA before inclusion in the study may be related either to the fact that the back pain symptoms were relatively mild or to ignorance of general physicians for these alarm symptoms,” the authors wrote.

One person said they had past or present peripheral arthritis but none reported enthesitis or dactylitis.

While none of the subjects had arthritis, 16% reported at least one tender joint, and 22% had a modified Schober score of less than 4.5 cm, with 4% showing a chest expansion of less than 3.6 cm.

Researchers also examined whether HLA-B27 status had any impact on the first-degree relatives, as previous studies had suggested that SpA is more likely to present in HLA-B27–positive first-degree relatives.

However they found no differences between the HLA-B27–positive and HLA-B27–negative groups in terms of demographics, symptom history, disease activity, clinical examination, or laboratory or imaging data; a finding the authors described as “intriguing.”

“However, if confirmed in a larger sample set, further follow-up of these FDRs will allow us to determine if FDRs showing signs and symptoms of SpA will evolve to more active and severe disease, independently of HLA-B27 status or, alternatively, if the presence of HLA-B27 may promote exacerbation and persistence of subclinical pathology.”

The study was supported by the Dutch Arthritis Foundation. No conflicts of interest were declared.

As many as one-third of healthy first-degree relatives of individuals with ankylosing spondylitis may meet the criteria for spondyloarthritis, according to results from a prospective cohort study.

Dr. Maureen C. Turina of the Amsterdam Rheumatology and Immunology Center at the University of Amsterdam and her coauthors enrolled 51 first-degree relatives of individuals with HLA-B27–positive ankylosing spondylitis in the study to see whether any of these otherwise healthy individuals showed early signs of the disease. They found that 17 (33%) of these first-degree relatives fulfilled any of the spondyloarthritis (SpA) classification criteria at baseline – a higher rate than reported in previous studies – and 7 (14%) met both the Assessment of Spondyloarthritis International Society (ASAS) criteria and European Spondyloarthropathy Study Group (ESSG) criteria.

©Rocky89/Thinkstock.com

The authors suggested that the higher rate, compared with previous studies, could be due to channeling bias, as individuals with clinical symptoms may have been more willing to participate in the study.

However, 4 of the 38 individuals who did not fulfill either of these criteria for SpA still showed imaging abnormalities – including syndesmophytes on the cervical spine and bone marrow edema in the sacroiliac joint.

The authors suggested these imaging abnormalities may represent a subclinical phase of SpA (Arthritis Rheumatol. 2016 May 23. doi: 10.1002/art.39766).

The participants who met the ASAS and/or ESSG classification criteria for SpA had more axial, entheseal, and joint pain, compared with those who did not meet the criteria. All of these patients also reported back pain, compared with 35% of those who did not fulfill the criteria.

However, the individuals meeting the SpA criteria had low overall disease scores, and did not show any increase in inflammatory serum markers.

“Importantly, some key features of SpA including the presence of peripheral disease or extra-articular manifestations and increased inflammatory parameters were only rarely observed in FDRs [first-degree relatives] and were also not different in those fulfilling the ASAS axSpA and/or ESSG classification criteria versus those who did not,” the authors reported.

“Future follow-up will learn if and which of these FDRs will evolve into the clinically established phase of SpA.”

When specifically asked, more than half (57%) of the first-degree relatives said they had back pain, and 40% said they had experienced or were experiencing arthralgia.

“The fact that these FDRs were not investigated for or diagnosed with axial SpA before inclusion in the study may be related either to the fact that the back pain symptoms were relatively mild or to ignorance of general physicians for these alarm symptoms,” the authors wrote.

One person said they had past or present peripheral arthritis but none reported enthesitis or dactylitis.

While none of the subjects had arthritis, 16% reported at least one tender joint, and 22% had a modified Schober score of less than 4.5 cm, with 4% showing a chest expansion of less than 3.6 cm.

Researchers also examined whether HLA-B27 status had any impact on the first-degree relatives, as previous studies had suggested that SpA is more likely to present in HLA-B27–positive first-degree relatives.

However they found no differences between the HLA-B27–positive and HLA-B27–negative groups in terms of demographics, symptom history, disease activity, clinical examination, or laboratory or imaging data; a finding the authors described as “intriguing.”

“However, if confirmed in a larger sample set, further follow-up of these FDRs will allow us to determine if FDRs showing signs and symptoms of SpA will evolve to more active and severe disease, independently of HLA-B27 status or, alternatively, if the presence of HLA-B27 may promote exacerbation and persistence of subclinical pathology.”

The study was supported by the Dutch Arthritis Foundation. No conflicts of interest were declared.

As many as one-third of healthy first-degree relatives of individuals with ankylosing spondylitis may meet the criteria for spondyloarthritis, according to results from a prospective cohort study.

Dr. Maureen C. Turina of the Amsterdam Rheumatology and Immunology Center at the University of Amsterdam and her coauthors enrolled 51 first-degree relatives of individuals with HLA-B27–positive ankylosing spondylitis in the study to see whether any of these otherwise healthy individuals showed early signs of the disease. They found that 17 (33%) of these first-degree relatives fulfilled any of the spondyloarthritis (SpA) classification criteria at baseline – a higher rate than reported in previous studies – and 7 (14%) met both the Assessment of Spondyloarthritis International Society (ASAS) criteria and European Spondyloarthropathy Study Group (ESSG) criteria.

©Rocky89/Thinkstock.com

The authors suggested that the higher rate, compared with previous studies, could be due to channeling bias, as individuals with clinical symptoms may have been more willing to participate in the study.

However, 4 of the 38 individuals who did not fulfill either of these criteria for SpA still showed imaging abnormalities – including syndesmophytes on the cervical spine and bone marrow edema in the sacroiliac joint.

The authors suggested these imaging abnormalities may represent a subclinical phase of SpA (Arthritis Rheumatol. 2016 May 23. doi: 10.1002/art.39766).

The participants who met the ASAS and/or ESSG classification criteria for SpA had more axial, entheseal, and joint pain, compared with those who did not meet the criteria. All of these patients also reported back pain, compared with 35% of those who did not fulfill the criteria.

However, the individuals meeting the SpA criteria had low overall disease scores, and did not show any increase in inflammatory serum markers.

“Importantly, some key features of SpA including the presence of peripheral disease or extra-articular manifestations and increased inflammatory parameters were only rarely observed in FDRs [first-degree relatives] and were also not different in those fulfilling the ASAS axSpA and/or ESSG classification criteria versus those who did not,” the authors reported.

“Future follow-up will learn if and which of these FDRs will evolve into the clinically established phase of SpA.”

When specifically asked, more than half (57%) of the first-degree relatives said they had back pain, and 40% said they had experienced or were experiencing arthralgia.

“The fact that these FDRs were not investigated for or diagnosed with axial SpA before inclusion in the study may be related either to the fact that the back pain symptoms were relatively mild or to ignorance of general physicians for these alarm symptoms,” the authors wrote.

One person said they had past or present peripheral arthritis but none reported enthesitis or dactylitis.

While none of the subjects had arthritis, 16% reported at least one tender joint, and 22% had a modified Schober score of less than 4.5 cm, with 4% showing a chest expansion of less than 3.6 cm.

Researchers also examined whether HLA-B27 status had any impact on the first-degree relatives, as previous studies had suggested that SpA is more likely to present in HLA-B27–positive first-degree relatives.

However they found no differences between the HLA-B27–positive and HLA-B27–negative groups in terms of demographics, symptom history, disease activity, clinical examination, or laboratory or imaging data; a finding the authors described as “intriguing.”

“However, if confirmed in a larger sample set, further follow-up of these FDRs will allow us to determine if FDRs showing signs and symptoms of SpA will evolve to more active and severe disease, independently of HLA-B27 status or, alternatively, if the presence of HLA-B27 may promote exacerbation and persistence of subclinical pathology.”

The study was supported by the Dutch Arthritis Foundation. No conflicts of interest were declared.

WASHINGTON – Physician organizations are calling on Congress to stop a proposed federal regulation that would test how Medicare pays for drugs administered in a physician’s office.

Subcommittee member Rep. Larry Bucshon (R-Ind.), a cardiothoracic surgeon, called the premise of the proposed rule – that physicians are making prescribing decisions based on the cost of drugs – “almost an insult to the medical profession.” He has introduced legislation, H.R. 5122, that would require the Centers for Medicare & Medicaid Services to rescind the proposed rule.

CMS argues in the proposed rule that the current payment formula – average sales price (ASP) plus 6% – incentivizes the use of expensive drugs over lower-cost alternatives. Therefore, the agency seeks to run a test – half of doctors would continue to receive ASP plus 6%, while others would receive ASP plus 2.5% and a flat fee of $16.80. The proposed rule also would test other value-based tools. At the May 17 hearing, physicians presented their concerns regarding the proposed rule.

“CMS has yet to produce any evidence indicating that physician prescribing patterns show any correlation to that of choosing higher priced drugs as opposed to appropriate therapeutic treatment for patients,” said Dr. Debra A. Patt, vice president of Texas Oncology. Dr. Patt testified on behalf of the American Society of Clinical Oncology, the Community Oncology Alliance, and the U.S. Oncology Network. “Additionally, there is no evidence that the payment changes contemplated by CMS’s model will improve the quality of care, or for that matter, ensure patients have access to the same level of care they are currently receiving.”Dr. Michael Schweitz, national advocacy chair of the Coalition of State Rheumatology Organizations (CSRO), cited CMS’s admission that this rule will likely have no impact on ASP.

“While we appreciate CMS’s attention to the topic of drug costs, we feel that this proposal is misguided,” Dr. Schweitz testified. “As CMS acknowledges in the rule, the proposed approach ‘does not directly address the manufacturer’s ASP, which is a more significant driver of drug expenditures than the add-on payment amount for Part B drugs.’ Given that a slash to the ASP add-on is unlikely to actually lower costs for patients ... and may jeopardize access, we have requested that CMS withdraw the model and we urge the committee to do the same.”

Dr. Patt also questioned ASP, noting that it is simply an average, and the prices actually paid by rural and small group providers could be higher than larger group and hospital practices – and that difference puts the smaller and rural practices at a potentially significant financial disadvantage.

“Average sales price is by its very nature an average,” Dr. Patt testified. “Some people will pay higher amounts for procurement and some people will pay lower amounts. Larger hospital systems and larger practices have the ability to have contracting arrangements where they purchase at a lower price. … Smaller practices disproportionately pay a higher amount.”

Small practices that are slated to receive ASP plus 2.5% and that flat fee “could be losing money on all of the drugs that they buy. It will be impossible for smaller practices in rural areas to be open,” she added, noting that such a situation could cause care to be shifted to hospital outpatient departments, raising costs as well as access issues. “Cutting provider reimbursement without addressing the ASP, the actual cost of the drug in the first place, is just the wrong approach,” Rep. Bucshon said.

According to the proposed rule, whether or not a practice is in the test or control group would be based on ZIP code. Dr. Patt also noted that if she were in a test ZIP code and a neighboring ZIP code was not, she might have to refer patients to that area still receiving ASP plus 6% and “not at my center.”

Witnesses at the hearing also condemned the way CMS devised the proposed tests. Unlike the recent work on the Medicare Access and CHIP Reauthorization Act regulations and more specialized programs like the Oncology Care Model, Dr. Schweitz and Dr. Patt both testified that CMS made no outreach to the provider community with regards to getting their input before issuing the proposed rule.

They also took exception to the scope of the proposed test, which covers 49 of the 50 states (Maryland is excluded) and provides no mechanism for physicians to opt out under the proposed rule.

“I do see this as an experiment, but we conduct clinical research at our cancer and patients have informed consent,” Dr Patt said.

Dr. Schweitz agreed. “When you look at the goals of this plan, initially it appeared that it was to direct a way to save costs. But in meeting with [the Center for Medicare & Medicaid Innovation], we were advised that this is budget neutral. … So the goal of the program is to collect information which makes it a study, a test. So if the goal is to collect information, and the patients are part of that process, they should be signing informed consent.”

Several physician organizations have called on CMS to withdraw the proposal.

“We are deeply concerned that because the new methodology will frequently not properly cover the cost of physician administration of infused drugs, they will be forced to stop offering patients the ability to receive infusion treatments,” the American College of Rheumatology wrote in comments submitted on the proposed rule. Likewise, CSRO “must oppose the Part B drug payment model as it suffers from serious procedural and substantive flaws that we believe render it unworkable – and it does nothing to actually address drug prices,” according its comments.

While the proposal has garnered backlash from several directions, rheumatologists are seeing it as particularly burdensome because of the high price of medications with very limited options to substitute for lower-cost alternatives.

“Although we certainly seek to control costs for patients and Medicare whenever possible, the proposed new methodology does not adequately consider the higher average cost many of our physicians have acquiring, handling, administering, and billing for drugs and biologics,” according to the comments submitted by the ACR.

Indeed, comments from CSRO point out that when factoring in budget sequestration, the actual reimbursement physicians are receiving is ASP plus 4.4%, and doctors are actually losing money on certain drug purchases.

Of additional concern is that the proposed rule does not address ASP itself.

“A far greater concern than the add-on percentage is the underlying ASP, and the steep, fast price increases that these medications show each quarter, according to comments from the CSRO.

From 2007 to 2016, first-quarter ASP for infliximab rose from $53.73 to $79.90; ASP for abatacept rose from $18.70 to $39.44, according to CSRO comments. “These ASP increases are unsustainable for both the Medicare program and its beneficiaries, and we would like to work with CMS to explore actual solutions to stem the increases in those underlying prices.”

In its comments, ACR proposed a number of potential paths forward, starting with certain practices that should be exempted from the proposed demonstration: physician groups with 25 or fewer physicians; physician-owned practices that are located in rural and medically underserved areas; reimbursement changes for drugs and biologics that do not have an alternative with more than a 20% ASP differential; and drugs and biologics where there are three or fewer members of the drug class or biologics.

ACR also proposed altering the add-on formula that takes into account the costs of storing and administering supplies.

“For example, CMS could use a formula for reimbursement of ASP plus 6% or $500 (whichever is lower),” ACR said in its comments. “This formula would allow CMS to effectively target spending on expensive drugs, while leaving in place reimbursement rates for cheaper drugs.”

Additionally, ACR called for CMS to delay the testing of more value-based tools until it understands the impact of the ASP changes that are to be tested under this proposal.

CSRO does not have any specific policy recommendations to replace or modify the proposed rule, but rather calls for CMS to bring together all stakeholders, including patients, providers, payers, and manufacturers to devise a system that would work to the benefit of all while ensuring the best outcomes for patients, Dr. Schweitz said in an interview.

[email protected]

WASHINGTON – Physician organizations are calling on Congress to stop a proposed federal regulation that would test how Medicare pays for drugs administered in a physician’s office.

Subcommittee member Rep. Larry Bucshon (R-Ind.), a cardiothoracic surgeon, called the premise of the proposed rule – that physicians are making prescribing decisions based on the cost of drugs – “almost an insult to the medical profession.” He has introduced legislation, H.R. 5122, that would require the Centers for Medicare & Medicaid Services to rescind the proposed rule.

CMS argues in the proposed rule that the current payment formula – average sales price (ASP) plus 6% – incentivizes the use of expensive drugs over lower-cost alternatives. Therefore, the agency seeks to run a test – half of doctors would continue to receive ASP plus 6%, while others would receive ASP plus 2.5% and a flat fee of $16.80. The proposed rule also would test other value-based tools. At the May 17 hearing, physicians presented their concerns regarding the proposed rule.

“CMS has yet to produce any evidence indicating that physician prescribing patterns show any correlation to that of choosing higher priced drugs as opposed to appropriate therapeutic treatment for patients,” said Dr. Debra A. Patt, vice president of Texas Oncology. Dr. Patt testified on behalf of the American Society of Clinical Oncology, the Community Oncology Alliance, and the U.S. Oncology Network. “Additionally, there is no evidence that the payment changes contemplated by CMS’s model will improve the quality of care, or for that matter, ensure patients have access to the same level of care they are currently receiving.”Dr. Michael Schweitz, national advocacy chair of the Coalition of State Rheumatology Organizations (CSRO), cited CMS’s admission that this rule will likely have no impact on ASP.

“While we appreciate CMS’s attention to the topic of drug costs, we feel that this proposal is misguided,” Dr. Schweitz testified. “As CMS acknowledges in the rule, the proposed approach ‘does not directly address the manufacturer’s ASP, which is a more significant driver of drug expenditures than the add-on payment amount for Part B drugs.’ Given that a slash to the ASP add-on is unlikely to actually lower costs for patients ... and may jeopardize access, we have requested that CMS withdraw the model and we urge the committee to do the same.”

Dr. Patt also questioned ASP, noting that it is simply an average, and the prices actually paid by rural and small group providers could be higher than larger group and hospital practices – and that difference puts the smaller and rural practices at a potentially significant financial disadvantage.

“Average sales price is by its very nature an average,” Dr. Patt testified. “Some people will pay higher amounts for procurement and some people will pay lower amounts. Larger hospital systems and larger practices have the ability to have contracting arrangements where they purchase at a lower price. … Smaller practices disproportionately pay a higher amount.”

Small practices that are slated to receive ASP plus 2.5% and that flat fee “could be losing money on all of the drugs that they buy. It will be impossible for smaller practices in rural areas to be open,” she added, noting that such a situation could cause care to be shifted to hospital outpatient departments, raising costs as well as access issues. “Cutting provider reimbursement without addressing the ASP, the actual cost of the drug in the first place, is just the wrong approach,” Rep. Bucshon said.

According to the proposed rule, whether or not a practice is in the test or control group would be based on ZIP code. Dr. Patt also noted that if she were in a test ZIP code and a neighboring ZIP code was not, she might have to refer patients to that area still receiving ASP plus 6% and “not at my center.”

Witnesses at the hearing also condemned the way CMS devised the proposed tests. Unlike the recent work on the Medicare Access and CHIP Reauthorization Act regulations and more specialized programs like the Oncology Care Model, Dr. Schweitz and Dr. Patt both testified that CMS made no outreach to the provider community with regards to getting their input before issuing the proposed rule.

They also took exception to the scope of the proposed test, which covers 49 of the 50 states (Maryland is excluded) and provides no mechanism for physicians to opt out under the proposed rule.

“I do see this as an experiment, but we conduct clinical research at our cancer and patients have informed consent,” Dr Patt said.

Dr. Schweitz agreed. “When you look at the goals of this plan, initially it appeared that it was to direct a way to save costs. But in meeting with [the Center for Medicare & Medicaid Innovation], we were advised that this is budget neutral. … So the goal of the program is to collect information which makes it a study, a test. So if the goal is to collect information, and the patients are part of that process, they should be signing informed consent.”

Several physician organizations have called on CMS to withdraw the proposal.

“We are deeply concerned that because the new methodology will frequently not properly cover the cost of physician administration of infused drugs, they will be forced to stop offering patients the ability to receive infusion treatments,” the American College of Rheumatology wrote in comments submitted on the proposed rule. Likewise, CSRO “must oppose the Part B drug payment model as it suffers from serious procedural and substantive flaws that we believe render it unworkable – and it does nothing to actually address drug prices,” according its comments.

While the proposal has garnered backlash from several directions, rheumatologists are seeing it as particularly burdensome because of the high price of medications with very limited options to substitute for lower-cost alternatives.

“Although we certainly seek to control costs for patients and Medicare whenever possible, the proposed new methodology does not adequately consider the higher average cost many of our physicians have acquiring, handling, administering, and billing for drugs and biologics,” according to the comments submitted by the ACR.

Indeed, comments from CSRO point out that when factoring in budget sequestration, the actual reimbursement physicians are receiving is ASP plus 4.4%, and doctors are actually losing money on certain drug purchases.

Of additional concern is that the proposed rule does not address ASP itself.

“A far greater concern than the add-on percentage is the underlying ASP, and the steep, fast price increases that these medications show each quarter, according to comments from the CSRO.

From 2007 to 2016, first-quarter ASP for infliximab rose from $53.73 to $79.90; ASP for abatacept rose from $18.70 to $39.44, according to CSRO comments. “These ASP increases are unsustainable for both the Medicare program and its beneficiaries, and we would like to work with CMS to explore actual solutions to stem the increases in those underlying prices.”

In its comments, ACR proposed a number of potential paths forward, starting with certain practices that should be exempted from the proposed demonstration: physician groups with 25 or fewer physicians; physician-owned practices that are located in rural and medically underserved areas; reimbursement changes for drugs and biologics that do not have an alternative with more than a 20% ASP differential; and drugs and biologics where there are three or fewer members of the drug class or biologics.

ACR also proposed altering the add-on formula that takes into account the costs of storing and administering supplies.

“For example, CMS could use a formula for reimbursement of ASP plus 6% or $500 (whichever is lower),” ACR said in its comments. “This formula would allow CMS to effectively target spending on expensive drugs, while leaving in place reimbursement rates for cheaper drugs.”

Additionally, ACR called for CMS to delay the testing of more value-based tools until it understands the impact of the ASP changes that are to be tested under this proposal.

CSRO does not have any specific policy recommendations to replace or modify the proposed rule, but rather calls for CMS to bring together all stakeholders, including patients, providers, payers, and manufacturers to devise a system that would work to the benefit of all while ensuring the best outcomes for patients, Dr. Schweitz said in an interview.

[email protected]

WASHINGTON – Physician organizations are calling on Congress to stop a proposed federal regulation that would test how Medicare pays for drugs administered in a physician’s office.

Subcommittee member Rep. Larry Bucshon (R-Ind.), a cardiothoracic surgeon, called the premise of the proposed rule – that physicians are making prescribing decisions based on the cost of drugs – “almost an insult to the medical profession.” He has introduced legislation, H.R. 5122, that would require the Centers for Medicare & Medicaid Services to rescind the proposed rule.

CMS argues in the proposed rule that the current payment formula – average sales price (ASP) plus 6% – incentivizes the use of expensive drugs over lower-cost alternatives. Therefore, the agency seeks to run a test – half of doctors would continue to receive ASP plus 6%, while others would receive ASP plus 2.5% and a flat fee of $16.80. The proposed rule also would test other value-based tools. At the May 17 hearing, physicians presented their concerns regarding the proposed rule.

“CMS has yet to produce any evidence indicating that physician prescribing patterns show any correlation to that of choosing higher priced drugs as opposed to appropriate therapeutic treatment for patients,” said Dr. Debra A. Patt, vice president of Texas Oncology. Dr. Patt testified on behalf of the American Society of Clinical Oncology, the Community Oncology Alliance, and the U.S. Oncology Network. “Additionally, there is no evidence that the payment changes contemplated by CMS’s model will improve the quality of care, or for that matter, ensure patients have access to the same level of care they are currently receiving.”Dr. Michael Schweitz, national advocacy chair of the Coalition of State Rheumatology Organizations (CSRO), cited CMS’s admission that this rule will likely have no impact on ASP.

“While we appreciate CMS’s attention to the topic of drug costs, we feel that this proposal is misguided,” Dr. Schweitz testified. “As CMS acknowledges in the rule, the proposed approach ‘does not directly address the manufacturer’s ASP, which is a more significant driver of drug expenditures than the add-on payment amount for Part B drugs.’ Given that a slash to the ASP add-on is unlikely to actually lower costs for patients ... and may jeopardize access, we have requested that CMS withdraw the model and we urge the committee to do the same.”

Dr. Patt also questioned ASP, noting that it is simply an average, and the prices actually paid by rural and small group providers could be higher than larger group and hospital practices – and that difference puts the smaller and rural practices at a potentially significant financial disadvantage.

“Average sales price is by its very nature an average,” Dr. Patt testified. “Some people will pay higher amounts for procurement and some people will pay lower amounts. Larger hospital systems and larger practices have the ability to have contracting arrangements where they purchase at a lower price. … Smaller practices disproportionately pay a higher amount.”

Small practices that are slated to receive ASP plus 2.5% and that flat fee “could be losing money on all of the drugs that they buy. It will be impossible for smaller practices in rural areas to be open,” she added, noting that such a situation could cause care to be shifted to hospital outpatient departments, raising costs as well as access issues. “Cutting provider reimbursement without addressing the ASP, the actual cost of the drug in the first place, is just the wrong approach,” Rep. Bucshon said.

According to the proposed rule, whether or not a practice is in the test or control group would be based on ZIP code. Dr. Patt also noted that if she were in a test ZIP code and a neighboring ZIP code was not, she might have to refer patients to that area still receiving ASP plus 6% and “not at my center.”

Witnesses at the hearing also condemned the way CMS devised the proposed tests. Unlike the recent work on the Medicare Access and CHIP Reauthorization Act regulations and more specialized programs like the Oncology Care Model, Dr. Schweitz and Dr. Patt both testified that CMS made no outreach to the provider community with regards to getting their input before issuing the proposed rule.

They also took exception to the scope of the proposed test, which covers 49 of the 50 states (Maryland is excluded) and provides no mechanism for physicians to opt out under the proposed rule.

“I do see this as an experiment, but we conduct clinical research at our cancer and patients have informed consent,” Dr Patt said.

Dr. Schweitz agreed. “When you look at the goals of this plan, initially it appeared that it was to direct a way to save costs. But in meeting with [the Center for Medicare & Medicaid Innovation], we were advised that this is budget neutral. … So the goal of the program is to collect information which makes it a study, a test. So if the goal is to collect information, and the patients are part of that process, they should be signing informed consent.”

Several physician organizations have called on CMS to withdraw the proposal.

“We are deeply concerned that because the new methodology will frequently not properly cover the cost of physician administration of infused drugs, they will be forced to stop offering patients the ability to receive infusion treatments,” the American College of Rheumatology wrote in comments submitted on the proposed rule. Likewise, CSRO “must oppose the Part B drug payment model as it suffers from serious procedural and substantive flaws that we believe render it unworkable – and it does nothing to actually address drug prices,” according its comments.

While the proposal has garnered backlash from several directions, rheumatologists are seeing it as particularly burdensome because of the high price of medications with very limited options to substitute for lower-cost alternatives.

“Although we certainly seek to control costs for patients and Medicare whenever possible, the proposed new methodology does not adequately consider the higher average cost many of our physicians have acquiring, handling, administering, and billing for drugs and biologics,” according to the comments submitted by the ACR.

Indeed, comments from CSRO point out that when factoring in budget sequestration, the actual reimbursement physicians are receiving is ASP plus 4.4%, and doctors are actually losing money on certain drug purchases.

Of additional concern is that the proposed rule does not address ASP itself.

“A far greater concern than the add-on percentage is the underlying ASP, and the steep, fast price increases that these medications show each quarter, according to comments from the CSRO.

From 2007 to 2016, first-quarter ASP for infliximab rose from $53.73 to $79.90; ASP for abatacept rose from $18.70 to $39.44, according to CSRO comments. “These ASP increases are unsustainable for both the Medicare program and its beneficiaries, and we would like to work with CMS to explore actual solutions to stem the increases in those underlying prices.”

In its comments, ACR proposed a number of potential paths forward, starting with certain practices that should be exempted from the proposed demonstration: physician groups with 25 or fewer physicians; physician-owned practices that are located in rural and medically underserved areas; reimbursement changes for drugs and biologics that do not have an alternative with more than a 20% ASP differential; and drugs and biologics where there are three or fewer members of the drug class or biologics.

ACR also proposed altering the add-on formula that takes into account the costs of storing and administering supplies.

“For example, CMS could use a formula for reimbursement of ASP plus 6% or $500 (whichever is lower),” ACR said in its comments. “This formula would allow CMS to effectively target spending on expensive drugs, while leaving in place reimbursement rates for cheaper drugs.”

Additionally, ACR called for CMS to delay the testing of more value-based tools until it understands the impact of the ASP changes that are to be tested under this proposal.

CSRO does not have any specific policy recommendations to replace or modify the proposed rule, but rather calls for CMS to bring together all stakeholders, including patients, providers, payers, and manufacturers to devise a system that would work to the benefit of all while ensuring the best outcomes for patients, Dr. Schweitz said in an interview.

[email protected]

MAUI, HAWAII – The consensus among gastroenterologists with expertise in inflammatory bowel disease is that continuation of biologics or immunomodulators in affected women throughout pregnancy and breastfeeding poses no increased risks to the fetus – and therein lies a message for rheumatologists and obstetricians, Dr. Uma Mahadevan said at the 2016 Rheumatology Winter Clinical Symposium.

“The risk of uncontrolled disease must be weighed against the risk of medical therapy. And this is something that is often missed,” according to Dr. Mahadevan, professor of medicine and co–medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.

Gastroenterologists – at least, those whose practices focus on inflammatory bowel disease (IBD) – have led the way within medicine in terms of establishing the safety of biologics and immunomodulators such as azathioprine in pregnant women with chronic inflammatory diseases and their babies. And having accomplished that, they have been ahead of the curve in terms of continuing such therapy throughout pregnancy and breastfeeding. That’s because active Crohn’s disease and ulcerative colitis are particularly common in women during their childbearing years. And a disease flare during pregnancy is associated with a markedly increased risk of preterm birth and other adverse outcomes.

Gastroenterologists’ longstanding interest in the safety to mother and fetus of continued use of effective, potent medications throughout pregnancy was the impetus for the ongoing prospective U.S. Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes (PIANO) study, now in its ninth year, with an enrollment of roughly 1,500 women with IBD. The study has included comparisons of outcomes of women on different medications during pregnancy versus unmedicated women.

In multiple publications, Dr. Mahadevan and other PIANO investigators have established that increased IBD activity adversely affects pregnancy outcomes, and that stabilization of disease and effective maintenance therapy throughout pregnancy is important. The PIANO group has demonstrated that IBD medication exposure well into the third trimester in patients in sustained remission was not associated with an increase in congenital anomalies, spontaneous abortions, intrauterine growth restriction, or low birth weight.

To the surprise of many gastroenterologists, the PIANO study has shown that women with Crohn’s disease generally have smoother pregnancies than do those with ulcerative colitis, who tend to get sicker and have more complications.

Since PIANO data show an increased rate of preterm birth and low birth weight in IBD patients on combination therapy with azathioprine plus a biologic throughout pregnancy, Dr. Mahadevan and others try to discontinue the azathioprine, even though the need for combination therapy is a marker for patients with more severe disease.

Anti-TNF-alpha use during third trimester

Of particular interest to rheumatologists, who rely heavily on many of the same biologic agents gastroenterologists use to treat IBD, the use of anti–tumor necrosis factor–alpha biologics in the third trimester was not associated with an increase in preterm birth or maternal disease activity in the third trimester or the first 4 months post partum. When women on certolizumab pegol (Cimzia) during the third trimester were excluded from the analysis, since this biologic uniquely does not cross the placenta at all, the most recent PIANO data show a modest yet statistically significant 35% increase in infections in infants at age 12 months whose mothers were on other biologics in the third trimester. But Dr. Mahadevan said she doesn’t yet consider this finding definitive.

“It’s still a small group of patients, and every year when we update the results the infant infection risk goes back and forth from statistically significant to nonsignificant. I think there’s a signal here; we just need to keep collecting more data,” she said.

Particularly reassuring is the finding that the offspring of PIANO participants who had in utero exposure to biologics and immunomodulators didn’t have any developmental delay, compared with unexposed babies, according to the validated Ages and Stages Questionnaire at ages 1, 2, 3, and 4 years and Denver Childhood Developmental Score at months 4, 9, and 12.

“These kids do great later in life. Actually, they have better scores than unexposed kids. Not to say that biologics make your kid smarter. It probably has to do with better IBD control,” Dr. Mahadevan said.

Effects while breastfeeding

Breastfeeding while on biologics or azathioprine didn’t adversely affect infant growth, infection rate, or developmental milestones. More specifically, levels of biologics in the mothers, babies, or cord serum were not associated with the likelihood of a neonatal intensive care unit stay, an increase in infant infections, or achievement of developmental milestones.

“Almost all the agents are detectable in breast milk, but only at the nanogram level. We tell all our patients on biologics they can breastfeed. It doesn’t matter when their last dose was, don’t worry about it,” the gastroenterologist said.

Importance of preconception counseling

Key practical lessons she has learned in taking care of large numbers of patients with severe IBD referred to her tertiary center include the importance of preconception counseling. A woman should stop methotrexate at least 3 months prior to conception. Providing information on medication safety and the risks of poorly controlled disease helps in adherence.

It’s best to communicate with the patient’s obstetrician about the importance of continuing her IBD therapy during pregnancy before she becomes pregnant.

“It’s better to have this discussion ahead of time and have a plan in place. Once a patient is pregnant it’s very difficult if her doula or someone else has told them to stop a medication to convince them to continue it,” said Dr. Mahadevan.

All women with IBD should be followed as high-risk pregnancies. Mode of delivery is at the discretion of the obstetrician unless the patient has an open rectovaginal fistula; even if it’s inactive, cesarean delivery is preferable in that situation, she said.

Steps taken in the third trimester

In the third trimester, she routinely sends a letter to the patient’s pediatrician requesting no live virus vaccines in the coming baby’s first 6 months – in the United States, that’s the rotavirus vaccine – if the infant was exposed in utero to a biologic other than certolizumab pegol, but that all other vaccines can be given on schedule. She also asks that the pediatrician monitor an exposed baby for infections.

“That being said, there have been 20-plus exposures to rotavirus vaccine in the first 6 months of life recorded in the PIANO registry in the infants of mothers on biologics and we haven’t seen any adverse events. So maybe the CDC is overstating the risk, but at this point the rule is still no live virus vaccines,” she said.

She tries to time her last dose of biologic agents during pregnancy as follows: at week 30-32 for infliximab or vedolizumab and week 36-38 for adalimumab or golimumab. As for certolizumab pegol, “they can take that on their way to labor and delivery,” she quipped.

“I give the next dose of a biologic agent soon after delivery, often while the patient is still in the hospital, 24 hours after vaginal delivery and 48 hours after a C-section, assuming no infection,” Dr. Mahadevan said.

The elements of her approach to management of the pregnant patient with IBD are in accord with a recent report, The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy, in which she participated (Gastroenterology. 2016 Mar;150[3]:734-57).

Rheumatologists’ habits with biologics in pregnancy

Dr. John J. Cush rose from the audience to observe that the situation in rheumatology with regard to biologics in pregnancy is quite a bit different from what’s going on in gastroenterology.

“I think a lot of rheumatologists don’t let their patients get pregnant on biologics for fear of what may happen. And that’s because they don’t know the data. I think you’ve shown very clearly that you can get pregnant on biologics and do well. But for many of us who do allow our patients to get pregnant on biologic monotherapy, the practice is to stop it once they get pregnant. The idea is we want them to be in a very deep remission to increase the odds of getting pregnant and having a successful pregnancy, but then we stop the drug and we assume the disease state is going to stay the same. Often, though, it doesn’t stay the same, it gets worse. Yet this is a common practice in rheumatology. What’s your response?” asked Dr. Cush, professor of medicine and rheumatology at Baylor University Medical Center, Dallas, and director of clinical rheumatology at the Baylor Research Institute.

“I think in IBD it’s very clear that patients with active disease in pregnancy do much, much worse,” Dr. Mahadevan replied. “They have preterm birth, they get very sick, they’re hospitalized and placed on steroids. So for us, the benefit is very clear. I don’t know the data in rheumatoid arthritis – whether active disease leads to increased complication rates – but I do know from colleagues that in the postpartum period women with poorly controlled rheumatoid arthritis can’t take care of their baby because their hands are so damaged. And that’s a big deal.

“So when you see that the drugs are not associated with an increased risk of birth defects and on monotherapy there’s no increase in infections and other complications, you’d think that in the right patient continuing treatment until the late third trimester would be the way to go, especially since if you’ve put the patient on a biologic it must mean she has severe disease,” the gastroenterologist observed.

Dr. Roy Fleischmann of the University of Texas, Dallas, asked why gastroenterologists don’t put all IBD patients of childbearing age on certolizumab pegol if they need biologic therapy, since it doesn’t cross the placenta.

“Maybe IBD is different, but our biologics don’t necessarily have the longest persistence,” Dr. Mahadevan replied. “If you start a woman on certolizumab pegol at age 20 the chances of her still being on it at 28 are probably pretty low.”

Conference director Dr. Arthur Kavanaugh, professor of medicine at the University of California, San Diego, asked if the message regarding management of IBD in pregnancy being put forth by Dr. Mahadevan and the IBD in Pregnancy Consensus Group has gained wide acceptance by gastroenterologists across the country.

“I think the people who do IBD as a concentrated practice, whether in private or academic practice, are very aware of this literature,” she said.

“In general, IBD has become more and more centered among a group of people who want to take care of IBD. If you look at the big private practices, they have a hepatitis C person, an IBD person, and everyone else just wants to scope. I think the message is getting across to non-IBD gastroenterologists, but there is some confusion because the Europeans are very firm about stopping biologics at 22 weeks’ gestation if the patient is in deep remission and we in North America continue treatment,” said Dr. Mahadevan.

Her work with the PIANO study is funded by the Crohn’s and Colitis Foundation of America. In addition, Dr. Mahadevan disclosed ties to more than half a dozen pharmaceutical companies.

[email protected]

MAUI, HAWAII – The consensus among gastroenterologists with expertise in inflammatory bowel disease is that continuation of biologics or immunomodulators in affected women throughout pregnancy and breastfeeding poses no increased risks to the fetus – and therein lies a message for rheumatologists and obstetricians, Dr. Uma Mahadevan said at the 2016 Rheumatology Winter Clinical Symposium.

“The risk of uncontrolled disease must be weighed against the risk of medical therapy. And this is something that is often missed,” according to Dr. Mahadevan, professor of medicine and co–medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.

Gastroenterologists – at least, those whose practices focus on inflammatory bowel disease (IBD) – have led the way within medicine in terms of establishing the safety of biologics and immunomodulators such as azathioprine in pregnant women with chronic inflammatory diseases and their babies. And having accomplished that, they have been ahead of the curve in terms of continuing such therapy throughout pregnancy and breastfeeding. That’s because active Crohn’s disease and ulcerative colitis are particularly common in women during their childbearing years. And a disease flare during pregnancy is associated with a markedly increased risk of preterm birth and other adverse outcomes.

Gastroenterologists’ longstanding interest in the safety to mother and fetus of continued use of effective, potent medications throughout pregnancy was the impetus for the ongoing prospective U.S. Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes (PIANO) study, now in its ninth year, with an enrollment of roughly 1,500 women with IBD. The study has included comparisons of outcomes of women on different medications during pregnancy versus unmedicated women.

In multiple publications, Dr. Mahadevan and other PIANO investigators have established that increased IBD activity adversely affects pregnancy outcomes, and that stabilization of disease and effective maintenance therapy throughout pregnancy is important. The PIANO group has demonstrated that IBD medication exposure well into the third trimester in patients in sustained remission was not associated with an increase in congenital anomalies, spontaneous abortions, intrauterine growth restriction, or low birth weight.

To the surprise of many gastroenterologists, the PIANO study has shown that women with Crohn’s disease generally have smoother pregnancies than do those with ulcerative colitis, who tend to get sicker and have more complications.

Since PIANO data show an increased rate of preterm birth and low birth weight in IBD patients on combination therapy with azathioprine plus a biologic throughout pregnancy, Dr. Mahadevan and others try to discontinue the azathioprine, even though the need for combination therapy is a marker for patients with more severe disease.

Anti-TNF-alpha use during third trimester

Of particular interest to rheumatologists, who rely heavily on many of the same biologic agents gastroenterologists use to treat IBD, the use of anti–tumor necrosis factor–alpha biologics in the third trimester was not associated with an increase in preterm birth or maternal disease activity in the third trimester or the first 4 months post partum. When women on certolizumab pegol (Cimzia) during the third trimester were excluded from the analysis, since this biologic uniquely does not cross the placenta at all, the most recent PIANO data show a modest yet statistically significant 35% increase in infections in infants at age 12 months whose mothers were on other biologics in the third trimester. But Dr. Mahadevan said she doesn’t yet consider this finding definitive.

“It’s still a small group of patients, and every year when we update the results the infant infection risk goes back and forth from statistically significant to nonsignificant. I think there’s a signal here; we just need to keep collecting more data,” she said.

Particularly reassuring is the finding that the offspring of PIANO participants who had in utero exposure to biologics and immunomodulators didn’t have any developmental delay, compared with unexposed babies, according to the validated Ages and Stages Questionnaire at ages 1, 2, 3, and 4 years and Denver Childhood Developmental Score at months 4, 9, and 12.

“These kids do great later in life. Actually, they have better scores than unexposed kids. Not to say that biologics make your kid smarter. It probably has to do with better IBD control,” Dr. Mahadevan said.

Effects while breastfeeding

Breastfeeding while on biologics or azathioprine didn’t adversely affect infant growth, infection rate, or developmental milestones. More specifically, levels of biologics in the mothers, babies, or cord serum were not associated with the likelihood of a neonatal intensive care unit stay, an increase in infant infections, or achievement of developmental milestones.

“Almost all the agents are detectable in breast milk, but only at the nanogram level. We tell all our patients on biologics they can breastfeed. It doesn’t matter when their last dose was, don’t worry about it,” the gastroenterologist said.

Importance of preconception counseling

Key practical lessons she has learned in taking care of large numbers of patients with severe IBD referred to her tertiary center include the importance of preconception counseling. A woman should stop methotrexate at least 3 months prior to conception. Providing information on medication safety and the risks of poorly controlled disease helps in adherence.

It’s best to communicate with the patient’s obstetrician about the importance of continuing her IBD therapy during pregnancy before she becomes pregnant.

“It’s better to have this discussion ahead of time and have a plan in place. Once a patient is pregnant it’s very difficult if her doula or someone else has told them to stop a medication to convince them to continue it,” said Dr. Mahadevan.

All women with IBD should be followed as high-risk pregnancies. Mode of delivery is at the discretion of the obstetrician unless the patient has an open rectovaginal fistula; even if it’s inactive, cesarean delivery is preferable in that situation, she said.

Steps taken in the third trimester

In the third trimester, she routinely sends a letter to the patient’s pediatrician requesting no live virus vaccines in the coming baby’s first 6 months – in the United States, that’s the rotavirus vaccine – if the infant was exposed in utero to a biologic other than certolizumab pegol, but that all other vaccines can be given on schedule. She also asks that the pediatrician monitor an exposed baby for infections.

“That being said, there have been 20-plus exposures to rotavirus vaccine in the first 6 months of life recorded in the PIANO registry in the infants of mothers on biologics and we haven’t seen any adverse events. So maybe the CDC is overstating the risk, but at this point the rule is still no live virus vaccines,” she said.

She tries to time her last dose of biologic agents during pregnancy as follows: at week 30-32 for infliximab or vedolizumab and week 36-38 for adalimumab or golimumab. As for certolizumab pegol, “they can take that on their way to labor and delivery,” she quipped.

“I give the next dose of a biologic agent soon after delivery, often while the patient is still in the hospital, 24 hours after vaginal delivery and 48 hours after a C-section, assuming no infection,” Dr. Mahadevan said.

The elements of her approach to management of the pregnant patient with IBD are in accord with a recent report, The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy, in which she participated (Gastroenterology. 2016 Mar;150[3]:734-57).

Rheumatologists’ habits with biologics in pregnancy

Dr. John J. Cush rose from the audience to observe that the situation in rheumatology with regard to biologics in pregnancy is quite a bit different from what’s going on in gastroenterology.

“I think a lot of rheumatologists don’t let their patients get pregnant on biologics for fear of what may happen. And that’s because they don’t know the data. I think you’ve shown very clearly that you can get pregnant on biologics and do well. But for many of us who do allow our patients to get pregnant on biologic monotherapy, the practice is to stop it once they get pregnant. The idea is we want them to be in a very deep remission to increase the odds of getting pregnant and having a successful pregnancy, but then we stop the drug and we assume the disease state is going to stay the same. Often, though, it doesn’t stay the same, it gets worse. Yet this is a common practice in rheumatology. What’s your response?” asked Dr. Cush, professor of medicine and rheumatology at Baylor University Medical Center, Dallas, and director of clinical rheumatology at the Baylor Research Institute.

“I think in IBD it’s very clear that patients with active disease in pregnancy do much, much worse,” Dr. Mahadevan replied. “They have preterm birth, they get very sick, they’re hospitalized and placed on steroids. So for us, the benefit is very clear. I don’t know the data in rheumatoid arthritis – whether active disease leads to increased complication rates – but I do know from colleagues that in the postpartum period women with poorly controlled rheumatoid arthritis can’t take care of their baby because their hands are so damaged. And that’s a big deal.

“So when you see that the drugs are not associated with an increased risk of birth defects and on monotherapy there’s no increase in infections and other complications, you’d think that in the right patient continuing treatment until the late third trimester would be the way to go, especially since if you’ve put the patient on a biologic it must mean she has severe disease,” the gastroenterologist observed.

Dr. Roy Fleischmann of the University of Texas, Dallas, asked why gastroenterologists don’t put all IBD patients of childbearing age on certolizumab pegol if they need biologic therapy, since it doesn’t cross the placenta.

“Maybe IBD is different, but our biologics don’t necessarily have the longest persistence,” Dr. Mahadevan replied. “If you start a woman on certolizumab pegol at age 20 the chances of her still being on it at 28 are probably pretty low.”

Conference director Dr. Arthur Kavanaugh, professor of medicine at the University of California, San Diego, asked if the message regarding management of IBD in pregnancy being put forth by Dr. Mahadevan and the IBD in Pregnancy Consensus Group has gained wide acceptance by gastroenterologists across the country.

“I think the people who do IBD as a concentrated practice, whether in private or academic practice, are very aware of this literature,” she said.

“In general, IBD has become more and more centered among a group of people who want to take care of IBD. If you look at the big private practices, they have a hepatitis C person, an IBD person, and everyone else just wants to scope. I think the message is getting across to non-IBD gastroenterologists, but there is some confusion because the Europeans are very firm about stopping biologics at 22 weeks’ gestation if the patient is in deep remission and we in North America continue treatment,” said Dr. Mahadevan.

Her work with the PIANO study is funded by the Crohn’s and Colitis Foundation of America. In addition, Dr. Mahadevan disclosed ties to more than half a dozen pharmaceutical companies.

[email protected]

MAUI, HAWAII – The consensus among gastroenterologists with expertise in inflammatory bowel disease is that continuation of biologics or immunomodulators in affected women throughout pregnancy and breastfeeding poses no increased risks to the fetus – and therein lies a message for rheumatologists and obstetricians, Dr. Uma Mahadevan said at the 2016 Rheumatology Winter Clinical Symposium.

“The risk of uncontrolled disease must be weighed against the risk of medical therapy. And this is something that is often missed,” according to Dr. Mahadevan, professor of medicine and co–medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.

Gastroenterologists – at least, those whose practices focus on inflammatory bowel disease (IBD) – have led the way within medicine in terms of establishing the safety of biologics and immunomodulators such as azathioprine in pregnant women with chronic inflammatory diseases and their babies. And having accomplished that, they have been ahead of the curve in terms of continuing such therapy throughout pregnancy and breastfeeding. That’s because active Crohn’s disease and ulcerative colitis are particularly common in women during their childbearing years. And a disease flare during pregnancy is associated with a markedly increased risk of preterm birth and other adverse outcomes.

Gastroenterologists’ longstanding interest in the safety to mother and fetus of continued use of effective, potent medications throughout pregnancy was the impetus for the ongoing prospective U.S. Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes (PIANO) study, now in its ninth year, with an enrollment of roughly 1,500 women with IBD. The study has included comparisons of outcomes of women on different medications during pregnancy versus unmedicated women.

In multiple publications, Dr. Mahadevan and other PIANO investigators have established that increased IBD activity adversely affects pregnancy outcomes, and that stabilization of disease and effective maintenance therapy throughout pregnancy is important. The PIANO group has demonstrated that IBD medication exposure well into the third trimester in patients in sustained remission was not associated with an increase in congenital anomalies, spontaneous abortions, intrauterine growth restriction, or low birth weight.

To the surprise of many gastroenterologists, the PIANO study has shown that women with Crohn’s disease generally have smoother pregnancies than do those with ulcerative colitis, who tend to get sicker and have more complications.

Since PIANO data show an increased rate of preterm birth and low birth weight in IBD patients on combination therapy with azathioprine plus a biologic throughout pregnancy, Dr. Mahadevan and others try to discontinue the azathioprine, even though the need for combination therapy is a marker for patients with more severe disease.

Anti-TNF-alpha use during third trimester

Of particular interest to rheumatologists, who rely heavily on many of the same biologic agents gastroenterologists use to treat IBD, the use of anti–tumor necrosis factor–alpha biologics in the third trimester was not associated with an increase in preterm birth or maternal disease activity in the third trimester or the first 4 months post partum. When women on certolizumab pegol (Cimzia) during the third trimester were excluded from the analysis, since this biologic uniquely does not cross the placenta at all, the most recent PIANO data show a modest yet statistically significant 35% increase in infections in infants at age 12 months whose mothers were on other biologics in the third trimester. But Dr. Mahadevan said she doesn’t yet consider this finding definitive.

“It’s still a small group of patients, and every year when we update the results the infant infection risk goes back and forth from statistically significant to nonsignificant. I think there’s a signal here; we just need to keep collecting more data,” she said.

Particularly reassuring is the finding that the offspring of PIANO participants who had in utero exposure to biologics and immunomodulators didn’t have any developmental delay, compared with unexposed babies, according to the validated Ages and Stages Questionnaire at ages 1, 2, 3, and 4 years and Denver Childhood Developmental Score at months 4, 9, and 12.

“These kids do great later in life. Actually, they have better scores than unexposed kids. Not to say that biologics make your kid smarter. It probably has to do with better IBD control,” Dr. Mahadevan said.

Effects while breastfeeding

Breastfeeding while on biologics or azathioprine didn’t adversely affect infant growth, infection rate, or developmental milestones. More specifically, levels of biologics in the mothers, babies, or cord serum were not associated with the likelihood of a neonatal intensive care unit stay, an increase in infant infections, or achievement of developmental milestones.

“Almost all the agents are detectable in breast milk, but only at the nanogram level. We tell all our patients on biologics they can breastfeed. It doesn’t matter when their last dose was, don’t worry about it,” the gastroenterologist said.

Importance of preconception counseling

Key practical lessons she has learned in taking care of large numbers of patients with severe IBD referred to her tertiary center include the importance of preconception counseling. A woman should stop methotrexate at least 3 months prior to conception. Providing information on medication safety and the risks of poorly controlled disease helps in adherence.

It’s best to communicate with the patient’s obstetrician about the importance of continuing her IBD therapy during pregnancy before she becomes pregnant.

“It’s better to have this discussion ahead of time and have a plan in place. Once a patient is pregnant it’s very difficult if her doula or someone else has told them to stop a medication to convince them to continue it,” said Dr. Mahadevan.

All women with IBD should be followed as high-risk pregnancies. Mode of delivery is at the discretion of the obstetrician unless the patient has an open rectovaginal fistula; even if it’s inactive, cesarean delivery is preferable in that situation, she said.

Steps taken in the third trimester

In the third trimester, she routinely sends a letter to the patient’s pediatrician requesting no live virus vaccines in the coming baby’s first 6 months – in the United States, that’s the rotavirus vaccine – if the infant was exposed in utero to a biologic other than certolizumab pegol, but that all other vaccines can be given on schedule. She also asks that the pediatrician monitor an exposed baby for infections.

“That being said, there have been 20-plus exposures to rotavirus vaccine in the first 6 months of life recorded in the PIANO registry in the infants of mothers on biologics and we haven’t seen any adverse events. So maybe the CDC is overstating the risk, but at this point the rule is still no live virus vaccines,” she said.

She tries to time her last dose of biologic agents during pregnancy as follows: at week 30-32 for infliximab or vedolizumab and week 36-38 for adalimumab or golimumab. As for certolizumab pegol, “they can take that on their way to labor and delivery,” she quipped.

“I give the next dose of a biologic agent soon after delivery, often while the patient is still in the hospital, 24 hours after vaginal delivery and 48 hours after a C-section, assuming no infection,” Dr. Mahadevan said.

The elements of her approach to management of the pregnant patient with IBD are in accord with a recent report, The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy, in which she participated (Gastroenterology. 2016 Mar;150[3]:734-57).

Rheumatologists’ habits with biologics in pregnancy

Dr. John J. Cush rose from the audience to observe that the situation in rheumatology with regard to biologics in pregnancy is quite a bit different from what’s going on in gastroenterology.

“I think a lot of rheumatologists don’t let their patients get pregnant on biologics for fear of what may happen. And that’s because they don’t know the data. I think you’ve shown very clearly that you can get pregnant on biologics and do well. But for many of us who do allow our patients to get pregnant on biologic monotherapy, the practice is to stop it once they get pregnant. The idea is we want them to be in a very deep remission to increase the odds of getting pregnant and having a successful pregnancy, but then we stop the drug and we assume the disease state is going to stay the same. Often, though, it doesn’t stay the same, it gets worse. Yet this is a common practice in rheumatology. What’s your response?” asked Dr. Cush, professor of medicine and rheumatology at Baylor University Medical Center, Dallas, and director of clinical rheumatology at the Baylor Research Institute.

“I think in IBD it’s very clear that patients with active disease in pregnancy do much, much worse,” Dr. Mahadevan replied. “They have preterm birth, they get very sick, they’re hospitalized and placed on steroids. So for us, the benefit is very clear. I don’t know the data in rheumatoid arthritis – whether active disease leads to increased complication rates – but I do know from colleagues that in the postpartum period women with poorly controlled rheumatoid arthritis can’t take care of their baby because their hands are so damaged. And that’s a big deal.

“So when you see that the drugs are not associated with an increased risk of birth defects and on monotherapy there’s no increase in infections and other complications, you’d think that in the right patient continuing treatment until the late third trimester would be the way to go, especially since if you’ve put the patient on a biologic it must mean she has severe disease,” the gastroenterologist observed.

Dr. Roy Fleischmann of the University of Texas, Dallas, asked why gastroenterologists don’t put all IBD patients of childbearing age on certolizumab pegol if they need biologic therapy, since it doesn’t cross the placenta.

“Maybe IBD is different, but our biologics don’t necessarily have the longest persistence,” Dr. Mahadevan replied. “If you start a woman on certolizumab pegol at age 20 the chances of her still being on it at 28 are probably pretty low.”

Conference director Dr. Arthur Kavanaugh, professor of medicine at the University of California, San Diego, asked if the message regarding management of IBD in pregnancy being put forth by Dr. Mahadevan and the IBD in Pregnancy Consensus Group has gained wide acceptance by gastroenterologists across the country.

“I think the people who do IBD as a concentrated practice, whether in private or academic practice, are very aware of this literature,” she said.

“In general, IBD has become more and more centered among a group of people who want to take care of IBD. If you look at the big private practices, they have a hepatitis C person, an IBD person, and everyone else just wants to scope. I think the message is getting across to non-IBD gastroenterologists, but there is some confusion because the Europeans are very firm about stopping biologics at 22 weeks’ gestation if the patient is in deep remission and we in North America continue treatment,” said Dr. Mahadevan.

Her work with the PIANO study is funded by the Crohn’s and Colitis Foundation of America. In addition, Dr. Mahadevan disclosed ties to more than half a dozen pharmaceutical companies.

[email protected]

GLASGOW – Switching patients on the anti–tumor necrosis factor drug Remicade to a biosimilar infliximab product resulted in good efficacy and tolerability with substantial cost savings in two real-world studies from the United Kingdom.

A total of 52 (88%) of 59 patients who had switched to the biosimilar infliximab CT-P13 (Inflectra) for the treatment of various indications for which Remicade is approved remained on the biosimilar after 10 months of follow-up and experienced comparable adverse events and similar levels of efficacy before and after switching, Dr. Lucy Parker of University Hospital Southampton NHS Foundation Trust reported at the British Society for Rheumatology annual conference. A second smaller study reported at the conference also showed similar results with the same infliximab biosimilar, which is also marketed as Remsima in Europe.

CT-P13 had efficacy, immunogenicity, and pharmacokinetic and pharmacodynamic parameters comparable to Remicade in 1-year follow-up data from the phase III randomized PLANETRAstudy (Arthritis Res Ther. 2016;18:82. doi: 10.1186/s13075-016-0981-6), but whether these study findings hold in a routine practice setting remains to be determined, Dr. Parker noted.

In Dr. Parker and colleagues’ study of data from the Southampton Biological Therapies Review Service, every patient was initially “seen in clinic and had the opportunity to speak to their consultant rheumatologist about the potential switchover from the originator drug to the new version,” she explained. Patients were then contacted directly by letter to explain the potential switch and given an information leaflet on Inflectra. They were also given access to a dedicated helpline number that could be used to re-explain the switch and discuss any concerns after switching had occurred.

In May 2015, all 59 patients being treated with Remicade were gradually switched over to the biosimilar version. Patients were reviewed after 3 months and then at 6-month intervals.

“Every single patient agreed to switch,” Dr. Parker observed. No patient used the helpline service or asked to talk with the consultant rheumatologist. One delegate noted during discussion that it was impressive that all patients agreed to switch, but Dr. Parker suggested that it was probably important that people were invited to switch rather being told that they would be switched. “If anyone had refused, then they would have been kept on Remicade,” she observed.

©BrianAJackson/Thinkstock.com

Dr. Parker noted that the patients were taking Remicade for various rheumatologic conditions, including 29 with rheumatoid arthritis (RA), 14 with ankylosing spondylitis (AS), 14 with psoriatic arthritis (PsA), and 2 with enteropathic arthritis. The mean age was 58.9 years, 51% of patients were female, mean disease duration was 18 years, and there was a mean of 5.7 years on Remicade before the switch. Patients had been diagnosed an average of 10 years before the first use of a biologic agent, 56% were also taking methotrexate, and 17% were on another disease-modifying antirheumatic drug (DMARD).

There was no significant difference in disease activity before or after switching, with respective mean 28-joint Disease Activity Scores of 3.4 and 3.3 and Bath Ankylosing Spondylitis Disease Activity Index scores of 3.7 and 3.6.

Dr. Parker noted that two 6-month periods before switching were compared to a 6-month period after switching and there were a similarly low number of cases reporting inefficacy, which was defined as any increase in symptoms or disease activity measure. Inefficacy was seen in one patient 12 months before the switch, two patients 6 months before the switch, and three patients after the switch. All three of the latter patients were switched back to Remicade, with one being then further switched to rituximab (Rituxan).

There were four adverse events in patients switched to the biosimilar versus three and four cases in the two 6-month periods before the switch. Adverse events after switching were widespread pain or myalgia and arthralgia after two infusions in two patients with PsA, multiple subjective symptoms such as dizziness and labile blood pressure and forgetfulness in another patient with PsA who also had these symptoms before the switch, and a case of chronic osteomyelitic foot infection in a patient with RA that also predated the switch. Biologic therapy was stopped in the RA patient, one of the PsA patients switched back to Remicade, and the other two were switched to ustekinumab (Stelara).

Dr. Parker reported that switching to the biosimilar has significantly cut the cost of treatment by £197,974 (about $291,000 USD) or 41.5% in their practice.

A team from St. George’s University Hospitals NHS Foundation Trust in London reported in a poster session similar findings after switching 31 patients to Remsima (Rheumatology [Oxford]. 2016;55[suppl 1]:i125-i126). Most switches occurred in RA patients (n = 18), followed by seven with AS and five with PsA. One patient did not switch following a consultant decision after the patient in question developed septic arthritis.

Dr. Ritu Malaiya and associates found equivalent efficacy responses in the vast majority of cases. Only one patient switched back to Remicade. Dr. Malaiya said that their experience of switching was, “on the whole, positive.” Effective planning and education of patients and staff around the switch was again considered vital and “instrumental to our early success,” the team reported. “Overall, patients were keen for others to benefit from more cost-effective drugs.”

Dr. Parker and Dr. Malaiya reported having no financial disclosures. Coauthors of the studies disclosed acting as consultants or receiving research grants from manufacturers of anti-TNF therapies.

GLASGOW – Switching patients on the anti–tumor necrosis factor drug Remicade to a biosimilar infliximab product resulted in good efficacy and tolerability with substantial cost savings in two real-world studies from the United Kingdom.

A total of 52 (88%) of 59 patients who had switched to the biosimilar infliximab CT-P13 (Inflectra) for the treatment of various indications for which Remicade is approved remained on the biosimilar after 10 months of follow-up and experienced comparable adverse events and similar levels of efficacy before and after switching, Dr. Lucy Parker of University Hospital Southampton NHS Foundation Trust reported at the British Society for Rheumatology annual conference. A second smaller study reported at the conference also showed similar results with the same infliximab biosimilar, which is also marketed as Remsima in Europe.

CT-P13 had efficacy, immunogenicity, and pharmacokinetic and pharmacodynamic parameters comparable to Remicade in 1-year follow-up data from the phase III randomized PLANETRAstudy (Arthritis Res Ther. 2016;18:82. doi: 10.1186/s13075-016-0981-6), but whether these study findings hold in a routine practice setting remains to be determined, Dr. Parker noted.

In Dr. Parker and colleagues’ study of data from the Southampton Biological Therapies Review Service, every patient was initially “seen in clinic and had the opportunity to speak to their consultant rheumatologist about the potential switchover from the originator drug to the new version,” she explained. Patients were then contacted directly by letter to explain the potential switch and given an information leaflet on Inflectra. They were also given access to a dedicated helpline number that could be used to re-explain the switch and discuss any concerns after switching had occurred.

In May 2015, all 59 patients being treated with Remicade were gradually switched over to the biosimilar version. Patients were reviewed after 3 months and then at 6-month intervals.

“Every single patient agreed to switch,” Dr. Parker observed. No patient used the helpline service or asked to talk with the consultant rheumatologist. One delegate noted during discussion that it was impressive that all patients agreed to switch, but Dr. Parker suggested that it was probably important that people were invited to switch rather being told that they would be switched. “If anyone had refused, then they would have been kept on Remicade,” she observed.

©BrianAJackson/Thinkstock.com

Dr. Parker noted that the patients were taking Remicade for various rheumatologic conditions, including 29 with rheumatoid arthritis (RA), 14 with ankylosing spondylitis (AS), 14 with psoriatic arthritis (PsA), and 2 with enteropathic arthritis. The mean age was 58.9 years, 51% of patients were female, mean disease duration was 18 years, and there was a mean of 5.7 years on Remicade before the switch. Patients had been diagnosed an average of 10 years before the first use of a biologic agent, 56% were also taking methotrexate, and 17% were on another disease-modifying antirheumatic drug (DMARD).

There was no significant difference in disease activity before or after switching, with respective mean 28-joint Disease Activity Scores of 3.4 and 3.3 and Bath Ankylosing Spondylitis Disease Activity Index scores of 3.7 and 3.6.

Dr. Parker noted that two 6-month periods before switching were compared to a 6-month period after switching and there were a similarly low number of cases reporting inefficacy, which was defined as any increase in symptoms or disease activity measure. Inefficacy was seen in one patient 12 months before the switch, two patients 6 months before the switch, and three patients after the switch. All three of the latter patients were switched back to Remicade, with one being then further switched to rituximab (Rituxan).

There were four adverse events in patients switched to the biosimilar versus three and four cases in the two 6-month periods before the switch. Adverse events after switching were widespread pain or myalgia and arthralgia after two infusions in two patients with PsA, multiple subjective symptoms such as dizziness and labile blood pressure and forgetfulness in another patient with PsA who also had these symptoms before the switch, and a case of chronic osteomyelitic foot infection in a patient with RA that also predated the switch. Biologic therapy was stopped in the RA patient, one of the PsA patients switched back to Remicade, and the other two were switched to ustekinumab (Stelara).

Dr. Parker reported that switching to the biosimilar has significantly cut the cost of treatment by £197,974 (about $291,000 USD) or 41.5% in their practice.

A team from St. George’s University Hospitals NHS Foundation Trust in London reported in a poster session similar findings after switching 31 patients to Remsima (Rheumatology [Oxford]. 2016;55[suppl 1]:i125-i126). Most switches occurred in RA patients (n = 18), followed by seven with AS and five with PsA. One patient did not switch following a consultant decision after the patient in question developed septic arthritis.

Dr. Ritu Malaiya and associates found equivalent efficacy responses in the vast majority of cases. Only one patient switched back to Remicade. Dr. Malaiya said that their experience of switching was, “on the whole, positive.” Effective planning and education of patients and staff around the switch was again considered vital and “instrumental to our early success,” the team reported. “Overall, patients were keen for others to benefit from more cost-effective drugs.”

Dr. Parker and Dr. Malaiya reported having no financial disclosures. Coauthors of the studies disclosed acting as consultants or receiving research grants from manufacturers of anti-TNF therapies.

GLASGOW – Switching patients on the anti–tumor necrosis factor drug Remicade to a biosimilar infliximab product resulted in good efficacy and tolerability with substantial cost savings in two real-world studies from the United Kingdom.

A total of 52 (88%) of 59 patients who had switched to the biosimilar infliximab CT-P13 (Inflectra) for the treatment of various indications for which Remicade is approved remained on the biosimilar after 10 months of follow-up and experienced comparable adverse events and similar levels of efficacy before and after switching, Dr. Lucy Parker of University Hospital Southampton NHS Foundation Trust reported at the British Society for Rheumatology annual conference. A second smaller study reported at the conference also showed similar results with the same infliximab biosimilar, which is also marketed as Remsima in Europe.

CT-P13 had efficacy, immunogenicity, and pharmacokinetic and pharmacodynamic parameters comparable to Remicade in 1-year follow-up data from the phase III randomized PLANETRAstudy (Arthritis Res Ther. 2016;18:82. doi: 10.1186/s13075-016-0981-6), but whether these study findings hold in a routine practice setting remains to be determined, Dr. Parker noted.

In Dr. Parker and colleagues’ study of data from the Southampton Biological Therapies Review Service, every patient was initially “seen in clinic and had the opportunity to speak to their consultant rheumatologist about the potential switchover from the originator drug to the new version,” she explained. Patients were then contacted directly by letter to explain the potential switch and given an information leaflet on Inflectra. They were also given access to a dedicated helpline number that could be used to re-explain the switch and discuss any concerns after switching had occurred.

In May 2015, all 59 patients being treated with Remicade were gradually switched over to the biosimilar version. Patients were reviewed after 3 months and then at 6-month intervals.

“Every single patient agreed to switch,” Dr. Parker observed. No patient used the helpline service or asked to talk with the consultant rheumatologist. One delegate noted during discussion that it was impressive that all patients agreed to switch, but Dr. Parker suggested that it was probably important that people were invited to switch rather being told that they would be switched. “If anyone had refused, then they would have been kept on Remicade,” she observed.

©BrianAJackson/Thinkstock.com

Dr. Parker noted that the patients were taking Remicade for various rheumatologic conditions, including 29 with rheumatoid arthritis (RA), 14 with ankylosing spondylitis (AS), 14 with psoriatic arthritis (PsA), and 2 with enteropathic arthritis. The mean age was 58.9 years, 51% of patients were female, mean disease duration was 18 years, and there was a mean of 5.7 years on Remicade before the switch. Patients had been diagnosed an average of 10 years before the first use of a biologic agent, 56% were also taking methotrexate, and 17% were on another disease-modifying antirheumatic drug (DMARD).

There was no significant difference in disease activity before or after switching, with respective mean 28-joint Disease Activity Scores of 3.4 and 3.3 and Bath Ankylosing Spondylitis Disease Activity Index scores of 3.7 and 3.6.

Dr. Parker noted that two 6-month periods before switching were compared to a 6-month period after switching and there were a similarly low number of cases reporting inefficacy, which was defined as any increase in symptoms or disease activity measure. Inefficacy was seen in one patient 12 months before the switch, two patients 6 months before the switch, and three patients after the switch. All three of the latter patients were switched back to Remicade, with one being then further switched to rituximab (Rituxan).

There were four adverse events in patients switched to the biosimilar versus three and four cases in the two 6-month periods before the switch. Adverse events after switching were widespread pain or myalgia and arthralgia after two infusions in two patients with PsA, multiple subjective symptoms such as dizziness and labile blood pressure and forgetfulness in another patient with PsA who also had these symptoms before the switch, and a case of chronic osteomyelitic foot infection in a patient with RA that also predated the switch. Biologic therapy was stopped in the RA patient, one of the PsA patients switched back to Remicade, and the other two were switched to ustekinumab (Stelara).

Dr. Parker reported that switching to the biosimilar has significantly cut the cost of treatment by £197,974 (about $291,000 USD) or 41.5% in their practice.

A team from St. George’s University Hospitals NHS Foundation Trust in London reported in a poster session similar findings after switching 31 patients to Remsima (Rheumatology [Oxford]. 2016;55[suppl 1]:i125-i126). Most switches occurred in RA patients (n = 18), followed by seven with AS and five with PsA. One patient did not switch following a consultant decision after the patient in question developed septic arthritis.

Dr. Ritu Malaiya and associates found equivalent efficacy responses in the vast majority of cases. Only one patient switched back to Remicade. Dr. Malaiya said that their experience of switching was, “on the whole, positive.” Effective planning and education of patients and staff around the switch was again considered vital and “instrumental to our early success,” the team reported. “Overall, patients were keen for others to benefit from more cost-effective drugs.”

Dr. Parker and Dr. Malaiya reported having no financial disclosures. Coauthors of the studies disclosed acting as consultants or receiving research grants from manufacturers of anti-TNF therapies.

GLASGOW, SCOTLAND – Treatment with the anti–interleukin-17A monoclonal antibody secukinumab improved a range of patient-reported outcome measures in a phase III trial of patients with ankylosing spondylitis.

Physical function, quality of life, fatigue, and work productivity were all significantly improved from baseline after 16 weeks of treatment with secukinumab (Cosentyx) versus placebo, and the effects were sustained for up to 1 year.

“PROMs [patient-reported outcome measures] are increasingly seen as the most important outcome measures [in trials] because of their importance to patients,” and they are very closely related to long-term retention and patients’ overall quality of life, Dr. Paul Emery said at the British Society for Rheumatology annual conference.

The new findings come from the MEASURE 2 study, a randomized, double-blind trial of 219 patients treated with one of two doses of secukinumab (150 mg or 75 mg) or placebo. Around 60% of the patient population was male, 95% were white, with a mean age around 42-44 years.

The primary endpoint data from the trial, which was the proportion of patients with at least as 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) response criteria at 16 weeks, were published recently (N Engl J Med. 2015;373:2534-48) with the results of the MEASURE 1 study. These showed that a significantly higher percentage of patients treated with the recommended dose of 150 mg, given as a subcutaneous injection every week for the first 3 weeks, then every 4 weeks from week 4, achieved ASAS 20 versus placebo (61% vs. 28%, P less than .001). Effects were sustained, with 62.5%-73.8% of patients still at ASAS 20 at 1 year depending on the type of data analysis performed, and 75% of those who switched from placebo at 16 weeks. The highest response rates were seen in patients who had not received prior anti-TNF therapy (82% vs. 60% for prior therapy at 1 year).

Changes in patients’ general and disease-specific quality of life from baseline to week 16 were predefined secondary endpoints assessed in the MEASURE 2 trial and were determined by the Short-Form (SF) 36 Physical Component Score (PCS) and the AS Quality of Life (ASQoL) questionnaire. Other exploratory endpoints included assessment of these measures at 1 year and the effect of treatment on the SF-36 Mental Component Score (MCS), Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue questionnaire, and the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire.

“One of the things about secukinumab is that you do get very fast responses in the things that matter,” said Dr. Emery of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds.

Improvement in SF-36 PCS showed improvement as early as week 4, with a mean increase of 6 points from baseline with secukinumab 150 mg versus only 1.9 points for placebo at week 16, and a sustained improvement of 8 points by 1 year. The minimal clinically important difference (MCID) for change in SF-36 is 2.5 points or more. There was not such a clear-cut difference for the SF-36 MCS, but there was a clinically significant improvement of about 4 points at 16 weeks and 6.5 by 1 year.

There was a significant improvement in quality of life versus placebo measured using the ASQoL instrument, with a mean reduction of 4 points for the recommended dose of secukinumab at 16 weeks versus a 1.4 reduction for placebo, and a 5.23 reduction for secukinumab at 1 year. Here the MCID is a change of 1.8 points, Dr. Emery reported.

The MCID for changes in the FACIT-Fatigue score is 4 points or more and this was passed by secukinumab 150 mg at both 16 weeks, with a change of 8 points versus 3.3 points for placebo, and at 1 year, with an increase of 11.5 points for secukinumab.

Work productivity impairment was also improved with active treatment, with mean changes in the WPAI-GH from baseline to week 16 of –16.36 versus –10.22 for placebo, and a sustained reduction of 21.33 at 1 year. Higher scores on this outcome measure mean that work productivity is more severely affected.

Secukinumab was approved for use in ankylosing spondylitis by the European Medicines Agency in October 2015 and more recently by the Food and Drug Administration in January this year. Its availability could be a potential “game changer” for these patients, Dr. Emery suggested, because its mode of action is different from other available therapies, notably the tumor necrosis factor inhibitors. It could become the treatment of choice for AS patients, partially those with enthesitis and psoriasis, at least before drugs that target interleukin (IL)-23 become available that may be better for addressing the spinal component of the disease, he noted during the Q&A that followed his presentation.

Data on radiographic progression will be presented separately, Dr. Emery noted during discussion. He added that secukinumab “certainly works” to reduce radiographic progression, but whether or not it is better than anti-TNF therapy remains to be seen. Because of the mechanism of action on IL-17A, secukinumab could potentially offer an advantage, he said.

“I think it is a game changer because we’ve had such restricted access to therapy previously,” Dr. Emery said. Now having drugs with two different modes of action is a bonus. Deciding which to use first, and in which patients, is the next issue to address.

Novartis supported the study. Dr. Emery has been a paid consultant to AbbVie, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche, UCB, Lilly, Samsung, and Sandoz.

GLASGOW, SCOTLAND – Treatment with the anti–interleukin-17A monoclonal antibody secukinumab improved a range of patient-reported outcome measures in a phase III trial of patients with ankylosing spondylitis.

Physical function, quality of life, fatigue, and work productivity were all significantly improved from baseline after 16 weeks of treatment with secukinumab (Cosentyx) versus placebo, and the effects were sustained for up to 1 year.

“PROMs [patient-reported outcome measures] are increasingly seen as the most important outcome measures [in trials] because of their importance to patients,” and they are very closely related to long-term retention and patients’ overall quality of life, Dr. Paul Emery said at the British Society for Rheumatology annual conference.

The new findings come from the MEASURE 2 study, a randomized, double-blind trial of 219 patients treated with one of two doses of secukinumab (150 mg or 75 mg) or placebo. Around 60% of the patient population was male, 95% were white, with a mean age around 42-44 years.

The primary endpoint data from the trial, which was the proportion of patients with at least as 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) response criteria at 16 weeks, were published recently (N Engl J Med. 2015;373:2534-48) with the results of the MEASURE 1 study. These showed that a significantly higher percentage of patients treated with the recommended dose of 150 mg, given as a subcutaneous injection every week for the first 3 weeks, then every 4 weeks from week 4, achieved ASAS 20 versus placebo (61% vs. 28%, P less than .001). Effects were sustained, with 62.5%-73.8% of patients still at ASAS 20 at 1 year depending on the type of data analysis performed, and 75% of those who switched from placebo at 16 weeks. The highest response rates were seen in patients who had not received prior anti-TNF therapy (82% vs. 60% for prior therapy at 1 year).

Changes in patients’ general and disease-specific quality of life from baseline to week 16 were predefined secondary endpoints assessed in the MEASURE 2 trial and were determined by the Short-Form (SF) 36 Physical Component Score (PCS) and the AS Quality of Life (ASQoL) questionnaire. Other exploratory endpoints included assessment of these measures at 1 year and the effect of treatment on the SF-36 Mental Component Score (MCS), Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue questionnaire, and the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire.

“One of the things about secukinumab is that you do get very fast responses in the things that matter,” said Dr. Emery of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds.

Improvement in SF-36 PCS showed improvement as early as week 4, with a mean increase of 6 points from baseline with secukinumab 150 mg versus only 1.9 points for placebo at week 16, and a sustained improvement of 8 points by 1 year. The minimal clinically important difference (MCID) for change in SF-36 is 2.5 points or more. There was not such a clear-cut difference for the SF-36 MCS, but there was a clinically significant improvement of about 4 points at 16 weeks and 6.5 by 1 year.

There was a significant improvement in quality of life versus placebo measured using the ASQoL instrument, with a mean reduction of 4 points for the recommended dose of secukinumab at 16 weeks versus a 1.4 reduction for placebo, and a 5.23 reduction for secukinumab at 1 year. Here the MCID is a change of 1.8 points, Dr. Emery reported.

The MCID for changes in the FACIT-Fatigue score is 4 points or more and this was passed by secukinumab 150 mg at both 16 weeks, with a change of 8 points versus 3.3 points for placebo, and at 1 year, with an increase of 11.5 points for secukinumab.

Work productivity impairment was also improved with active treatment, with mean changes in the WPAI-GH from baseline to week 16 of –16.36 versus –10.22 for placebo, and a sustained reduction of 21.33 at 1 year. Higher scores on this outcome measure mean that work productivity is more severely affected.

Secukinumab was approved for use in ankylosing spondylitis by the European Medicines Agency in October 2015 and more recently by the Food and Drug Administration in January this year. Its availability could be a potential “game changer” for these patients, Dr. Emery suggested, because its mode of action is different from other available therapies, notably the tumor necrosis factor inhibitors. It could become the treatment of choice for AS patients, partially those with enthesitis and psoriasis, at least before drugs that target interleukin (IL)-23 become available that may be better for addressing the spinal component of the disease, he noted during the Q&A that followed his presentation.

Data on radiographic progression will be presented separately, Dr. Emery noted during discussion. He added that secukinumab “certainly works” to reduce radiographic progression, but whether or not it is better than anti-TNF therapy remains to be seen. Because of the mechanism of action on IL-17A, secukinumab could potentially offer an advantage, he said.

“I think it is a game changer because we’ve had such restricted access to therapy previously,” Dr. Emery said. Now having drugs with two different modes of action is a bonus. Deciding which to use first, and in which patients, is the next issue to address.

Novartis supported the study. Dr. Emery has been a paid consultant to AbbVie, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche, UCB, Lilly, Samsung, and Sandoz.

GLASGOW, SCOTLAND – Treatment with the anti–interleukin-17A monoclonal antibody secukinumab improved a range of patient-reported outcome measures in a phase III trial of patients with ankylosing spondylitis.

Physical function, quality of life, fatigue, and work productivity were all significantly improved from baseline after 16 weeks of treatment with secukinumab (Cosentyx) versus placebo, and the effects were sustained for up to 1 year.

“PROMs [patient-reported outcome measures] are increasingly seen as the most important outcome measures [in trials] because of their importance to patients,” and they are very closely related to long-term retention and patients’ overall quality of life, Dr. Paul Emery said at the British Society for Rheumatology annual conference.

The new findings come from the MEASURE 2 study, a randomized, double-blind trial of 219 patients treated with one of two doses of secukinumab (150 mg or 75 mg) or placebo. Around 60% of the patient population was male, 95% were white, with a mean age around 42-44 years.

The primary endpoint data from the trial, which was the proportion of patients with at least as 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) response criteria at 16 weeks, were published recently (N Engl J Med. 2015;373:2534-48) with the results of the MEASURE 1 study. These showed that a significantly higher percentage of patients treated with the recommended dose of 150 mg, given as a subcutaneous injection every week for the first 3 weeks, then every 4 weeks from week 4, achieved ASAS 20 versus placebo (61% vs. 28%, P less than .001). Effects were sustained, with 62.5%-73.8% of patients still at ASAS 20 at 1 year depending on the type of data analysis performed, and 75% of those who switched from placebo at 16 weeks. The highest response rates were seen in patients who had not received prior anti-TNF therapy (82% vs. 60% for prior therapy at 1 year).

Changes in patients’ general and disease-specific quality of life from baseline to week 16 were predefined secondary endpoints assessed in the MEASURE 2 trial and were determined by the Short-Form (SF) 36 Physical Component Score (PCS) and the AS Quality of Life (ASQoL) questionnaire. Other exploratory endpoints included assessment of these measures at 1 year and the effect of treatment on the SF-36 Mental Component Score (MCS), Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue questionnaire, and the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire.

“One of the things about secukinumab is that you do get very fast responses in the things that matter,” said Dr. Emery of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds.

Improvement in SF-36 PCS showed improvement as early as week 4, with a mean increase of 6 points from baseline with secukinumab 150 mg versus only 1.9 points for placebo at week 16, and a sustained improvement of 8 points by 1 year. The minimal clinically important difference (MCID) for change in SF-36 is 2.5 points or more. There was not such a clear-cut difference for the SF-36 MCS, but there was a clinically significant improvement of about 4 points at 16 weeks and 6.5 by 1 year.

There was a significant improvement in quality of life versus placebo measured using the ASQoL instrument, with a mean reduction of 4 points for the recommended dose of secukinumab at 16 weeks versus a 1.4 reduction for placebo, and a 5.23 reduction for secukinumab at 1 year. Here the MCID is a change of 1.8 points, Dr. Emery reported.

The MCID for changes in the FACIT-Fatigue score is 4 points or more and this was passed by secukinumab 150 mg at both 16 weeks, with a change of 8 points versus 3.3 points for placebo, and at 1 year, with an increase of 11.5 points for secukinumab.

Work productivity impairment was also improved with active treatment, with mean changes in the WPAI-GH from baseline to week 16 of –16.36 versus –10.22 for placebo, and a sustained reduction of 21.33 at 1 year. Higher scores on this outcome measure mean that work productivity is more severely affected.

Secukinumab was approved for use in ankylosing spondylitis by the European Medicines Agency in October 2015 and more recently by the Food and Drug Administration in January this year. Its availability could be a potential “game changer” for these patients, Dr. Emery suggested, because its mode of action is different from other available therapies, notably the tumor necrosis factor inhibitors. It could become the treatment of choice for AS patients, partially those with enthesitis and psoriasis, at least before drugs that target interleukin (IL)-23 become available that may be better for addressing the spinal component of the disease, he noted during the Q&A that followed his presentation.

Data on radiographic progression will be presented separately, Dr. Emery noted during discussion. He added that secukinumab “certainly works” to reduce radiographic progression, but whether or not it is better than anti-TNF therapy remains to be seen. Because of the mechanism of action on IL-17A, secukinumab could potentially offer an advantage, he said.

“I think it is a game changer because we’ve had such restricted access to therapy previously,” Dr. Emery said. Now having drugs with two different modes of action is a bonus. Deciding which to use first, and in which patients, is the next issue to address.

Novartis supported the study. Dr. Emery has been a paid consultant to AbbVie, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche, UCB, Lilly, Samsung, and Sandoz.

Now that the Food and Drug Administration has approved Inflectra as the first biosimilar version of the anti–tumor necrosis factor-alpha agent Remicade, rheumatologists and patient advocacy groups are taking stock of how it may be used in practice, and what the future holds for biosimilar drugs, with so many questions still unanswered regarding price, substitution, and safety.

Joseph Riccio/Adirondack Health

Inflectra, approved in early April and given the generic name of infliximab-dyyb under the FDA’s nomenclature for biosimilar products, will have the same indications as Remicade. The agency extrapolated the clinical trial data that Inflectra’s South Korea–based manufacturer, Celltrion, submitted for rheumatoid arthritis and ankylosing spondylitis to all other indications for which Remicade is approved.

It’s currently unclear how the FDA will note which clinical data in Inflectra’s labeling come from Inflectra and which from Remicade, and the same concerns lie with future biosimilar approvals if their results are extrapolated to indications not tested to show biosimilarity in clinical trials.

Labeling questions

It’s concerning to rheumatologists and the patients who will be using them that biosimilars such as Inflectra are not subject to the same pivotal trial experience as the reference biologics on which they are based, according to Dr. Jonathan Krant, section chief of rheumatology for Adirondack Health Systems in Saranac Lake, N.Y., and medical director for CreakyJoints, a community of patients with arthritis and caregivers, and its larger parent nonprofit advocacy organization, the Global Healthy Living Foundation (GHLF).

While the unique regulatory requirements in the biosimilar approval pathway reduce development costs and could potentially make Inflectra’s average wholesale price 30% less than Remicade – as was the case when Inflectra was first on the market in Europe – it’s not known how reduced costs may affect the safety of biosimilars.

“It worries all of us that manufacturers may cut corners to manage the cost constraints imposed by managed care,” Dr. Krant said in an interview.

Given that U.S. rheumatologists don’t have experience with biosimilars, Dr. Krant is anticipating some push back. “I think some physicians are going to fight back and won’t want to prescribe them, even if mandated, because of concerns regarding patient safety,” he said.

In a written statement, Dr. Joan Von Feldt, president of the American College of Rheumatology, welcomed the potential benefits on access to care that cost-saving biosimilars may bring to the U.S. health care system, but also said that “the safety of our patients remains our highest priority. As such, we encourage the FDA to continue to apply distinct names for future biosimilars, and to maximize clarity in the labeling of biosimilars, specifically with respect to their interchangeable status and the origins (reference drug versus biosimilar) of clinical data upon which FDA approval is based.”

Inflectra met the FDA’s “very similar” criteria to be approved as a biosimilar by showing it has no clinically meaningful differences in terms of safety and effectiveness from Remicade, the agency said. According to FDA regulations, biosimilar products can have only minor differences in clinically inactive components and must have the same mechanism(s) of action (to the extent that it is known) and route(s) of administration, dosage form(s), and strength(s) as the reference product and can be approved only for the indication(s) and condition(s) of use that have been approved for the reference product.

However, it may not hold true that Inflectra will have the same efficacy and safety for all indications that Remicade had due to potential differences in the mechanism of action through which Remicade exerts its effect across indications, which in this case may apply to the indications for Crohn’s disease and ulcerative colitis.

Health Canada chose not to extrapolate the indications for Inflectra (known as Remsima in Canada) to Crohn’s disease and ulcerative colitis because of “observed differences in the level of afucosylation, Fc-gammaRIIIa receptor binding, and some in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) assays” that could not rule out the possibility that Inflectra and Remicade differ in their ability to induce ADCC. Unlike the other indications for Remicade, Health Canada said “ADCC cannot be ruled out as a mechanism of action in the inflammatory bowel diseases. This position is supported by the observation that certolizumab pegol, another anti-TNF [anti–tumor necrosis factor] that lacks the ability to induce ADCC, displays only marginal efficacy in Crohn’s patients, compared with other anti-TNFs, namely infliximab.”

Other organizations suggest that extrapolation of indications is only appropriate when it is benefiting the patient to the greatest extent possible.

“GHLF is okay with extrapolation of indication unless the mechanism of action for the therapy is either scientifically or therapeutically outdated,” Stephen Marmaras, state and national advocacy manager for the GHLF, said in an interview. “Patients are okay with extrapolating data in order to expedite the approval process as long as you are extrapolating to best in class therapy for a particular indication. What [the GHLF is] saying is we want biosimilars to be an improvement on what we have, not the lowest common denominator. We shouldn’t be extrapolating indications data from products that aren’t considered to be the best product for that indication.”

“If we’re just judging on expediting the approval process for indications that are not considered to be really treated well by this particular drug, you have to always assume that the insurance company is going to go with the lowest common denominator,” he added. “What that could lead to, from a slippery-slope perspective, is the chipping away of the use of cutting-edge therapies.”

Substitution concerns

Inflectra was not approved as interchangeable with Remicade or other infliximab biosimilars. The FDA has yet to define the regulatory requirements for interchangeability that are necessary to meet the requirements of the Biologics Price Competition and Innovation Act of 2009. That Act states that an approved biosimilar “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.”

A statement about implementation of the Act on the FDA website explains that for interchangeability, “a sponsor must demonstrate that the biosimilar product can be expected to produce the same clinical result as the reference product in any given patient and, for a biological product that is administered more than once, that the risk of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of maintaining the patient on the reference product.”

One of the biggest concerns that physicians have is that biosimilars will be substituted for the reference products without notification, Dr. Krant said. “State by state we’re looking at potential substitution rules which allow pharmacists to switch out these cheaper molecules for the reference product,” he said, and without timely notification, patients and rheumatologists won’t know whether it was the reference product or a biosimilar that was associated with an adverse event or loss of efficacy.

The ACR and patient advocacy organizations such as the GHLF are against forced switching of patients for nonmedical reasons. Patients’ and rheumatologists’ confidence in biosimilar safety will be key to their uptake and the overall expansion of access to biologics to more patients, Mr. Marmaras said.

Patient costs uncertain

Although rheumatologists hope that with biosimilars’ lower costs, access will expand, there is no guarantee it will do so by saving patients money.

“It’s a common misperception that a 30% decrease in the cost of a several thousand dollar-a-month drug is going to automatically open all the doors to access,” said Dr. Sean Fahey, a rheumatologist in Mooresville, N.C., and chair of the insurance subcommittee of the ACR’s Committee on Rheumatologic Care. “Most of my patients who use biologics do so either through copay cards from the pharmaceutical industry or through Medicare and a secondary [payer] covering their out-of-pocket costs for the infusible biologics. This is clearly saving the system money, which is important no doubt, but unless it’s significantly less expensive, it actually might not change the patient’s out-of pocket [cost] all that much.”

The patient assistance programs from biologics manufacturers that offer copay assistance, access hotlines, and administration benefits could be in jeopardy with the rise of biosimilars. Since the programs are bundled into the average wholesale price of the drug, the savings offered by the reduced wholesale price of biosimilars may squeeze them out, Dr. Krant said.

“There’s going to be a lot of hue and cry from the patients who cannot self-administer or have problems with compliance because of copays in the first place,” he predicted.

Another factor that could affect how much biosimilars such as Inflectra will be used is the amount of rebates or discounts that payers receive directly from the pharmaceutical manufacturers.

“We know for the Medicaid population what the average sales prices are, but for private payers, we don’t know if they’re giving 2%, 5%, 18%; we have no idea what the data are. This could affect how much market share Inflectra gets,” said Dr. Fahey, who is also president of the North Carolina Rheumatology Association.

It may be awhile before Inflectra is available on the U.S. market. In a statement following the approval of Inflectra, Remicade-maker Janssen said the “patents for Remicade remain valid and enforceable until September 2018. A commercial launch of Celltrion’s infliximab-dyyb in advance of this date would be an infringement of our patents, and we intend to defend our intellectual property rights.”

Janssen notes that its patient support program for Remicade “continues to offer a copay card for patients with commercial insurance that reduces the patient out-of-pocket cost to no more than $5 per infusion. Eligible uninsured and underinsured patients may be able to access Remicade through the Johnson & Johnson Patient Assistance Foundation.”

Pfizer, which owns the rights to marketing Inflectra in the United States, did not respond directly to a question about whether it would have a payment assistance program for Inflectra. “While we cannot comment on specific commercialization strategies at this time, we are working to bring these important therapies to market in the U.S. as quickly as possible,” said Rachel Hooper, Director of Public Affairs, West, for Pfizer.

It seems likely that once Inflectra does come to the market, new starts will account for many patients who will use the drug because of the lack of information available about whether there is, or is not, significant risk of immunogenicity with switching or loss of efficacy, Dr. Fahey said. “What is less certain is whether the payers will try to force us to move people from the Remicade brand to the infliximab biosimilar, and what the potential consequences of that is going to be.”

Dr. Krant, Dr. Fahey, and Mr. Marmaras had no relevant disclosures.

[email protected]

Now that the Food and Drug Administration has approved Inflectra as the first biosimilar version of the anti–tumor necrosis factor-alpha agent Remicade, rheumatologists and patient advocacy groups are taking stock of how it may be used in practice, and what the future holds for biosimilar drugs, with so many questions still unanswered regarding price, substitution, and safety.

Joseph Riccio/Adirondack Health

Inflectra, approved in early April and given the generic name of infliximab-dyyb under the FDA’s nomenclature for biosimilar products, will have the same indications as Remicade. The agency extrapolated the clinical trial data that Inflectra’s South Korea–based manufacturer, Celltrion, submitted for rheumatoid arthritis and ankylosing spondylitis to all other indications for which Remicade is approved.

It’s currently unclear how the FDA will note which clinical data in Inflectra’s labeling come from Inflectra and which from Remicade, and the same concerns lie with future biosimilar approvals if their results are extrapolated to indications not tested to show biosimilarity in clinical trials.

Labeling questions

It’s concerning to rheumatologists and the patients who will be using them that biosimilars such as Inflectra are not subject to the same pivotal trial experience as the reference biologics on which they are based, according to Dr. Jonathan Krant, section chief of rheumatology for Adirondack Health Systems in Saranac Lake, N.Y., and medical director for CreakyJoints, a community of patients with arthritis and caregivers, and its larger parent nonprofit advocacy organization, the Global Healthy Living Foundation (GHLF).

While the unique regulatory requirements in the biosimilar approval pathway reduce development costs and could potentially make Inflectra’s average wholesale price 30% less than Remicade – as was the case when Inflectra was first on the market in Europe – it’s not known how reduced costs may affect the safety of biosimilars.

“It worries all of us that manufacturers may cut corners to manage the cost constraints imposed by managed care,” Dr. Krant said in an interview.

Given that U.S. rheumatologists don’t have experience with biosimilars, Dr. Krant is anticipating some push back. “I think some physicians are going to fight back and won’t want to prescribe them, even if mandated, because of concerns regarding patient safety,” he said.

In a written statement, Dr. Joan Von Feldt, president of the American College of Rheumatology, welcomed the potential benefits on access to care that cost-saving biosimilars may bring to the U.S. health care system, but also said that “the safety of our patients remains our highest priority. As such, we encourage the FDA to continue to apply distinct names for future biosimilars, and to maximize clarity in the labeling of biosimilars, specifically with respect to their interchangeable status and the origins (reference drug versus biosimilar) of clinical data upon which FDA approval is based.”

Inflectra met the FDA’s “very similar” criteria to be approved as a biosimilar by showing it has no clinically meaningful differences in terms of safety and effectiveness from Remicade, the agency said. According to FDA regulations, biosimilar products can have only minor differences in clinically inactive components and must have the same mechanism(s) of action (to the extent that it is known) and route(s) of administration, dosage form(s), and strength(s) as the reference product and can be approved only for the indication(s) and condition(s) of use that have been approved for the reference product.

However, it may not hold true that Inflectra will have the same efficacy and safety for all indications that Remicade had due to potential differences in the mechanism of action through which Remicade exerts its effect across indications, which in this case may apply to the indications for Crohn’s disease and ulcerative colitis.

Health Canada chose not to extrapolate the indications for Inflectra (known as Remsima in Canada) to Crohn’s disease and ulcerative colitis because of “observed differences in the level of afucosylation, Fc-gammaRIIIa receptor binding, and some in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) assays” that could not rule out the possibility that Inflectra and Remicade differ in their ability to induce ADCC. Unlike the other indications for Remicade, Health Canada said “ADCC cannot be ruled out as a mechanism of action in the inflammatory bowel diseases. This position is supported by the observation that certolizumab pegol, another anti-TNF [anti–tumor necrosis factor] that lacks the ability to induce ADCC, displays only marginal efficacy in Crohn’s patients, compared with other anti-TNFs, namely infliximab.”

Other organizations suggest that extrapolation of indications is only appropriate when it is benefiting the patient to the greatest extent possible.

“GHLF is okay with extrapolation of indication unless the mechanism of action for the therapy is either scientifically or therapeutically outdated,” Stephen Marmaras, state and national advocacy manager for the GHLF, said in an interview. “Patients are okay with extrapolating data in order to expedite the approval process as long as you are extrapolating to best in class therapy for a particular indication. What [the GHLF is] saying is we want biosimilars to be an improvement on what we have, not the lowest common denominator. We shouldn’t be extrapolating indications data from products that aren’t considered to be the best product for that indication.”

“If we’re just judging on expediting the approval process for indications that are not considered to be really treated well by this particular drug, you have to always assume that the insurance company is going to go with the lowest common denominator,” he added. “What that could lead to, from a slippery-slope perspective, is the chipping away of the use of cutting-edge therapies.”

Substitution concerns

Inflectra was not approved as interchangeable with Remicade or other infliximab biosimilars. The FDA has yet to define the regulatory requirements for interchangeability that are necessary to meet the requirements of the Biologics Price Competition and Innovation Act of 2009. That Act states that an approved biosimilar “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.”

A statement about implementation of the Act on the FDA website explains that for interchangeability, “a sponsor must demonstrate that the biosimilar product can be expected to produce the same clinical result as the reference product in any given patient and, for a biological product that is administered more than once, that the risk of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of maintaining the patient on the reference product.”

One of the biggest concerns that physicians have is that biosimilars will be substituted for the reference products without notification, Dr. Krant said. “State by state we’re looking at potential substitution rules which allow pharmacists to switch out these cheaper molecules for the reference product,” he said, and without timely notification, patients and rheumatologists won’t know whether it was the reference product or a biosimilar that was associated with an adverse event or loss of efficacy.

The ACR and patient advocacy organizations such as the GHLF are against forced switching of patients for nonmedical reasons. Patients’ and rheumatologists’ confidence in biosimilar safety will be key to their uptake and the overall expansion of access to biologics to more patients, Mr. Marmaras said.

Patient costs uncertain

Although rheumatologists hope that with biosimilars’ lower costs, access will expand, there is no guarantee it will do so by saving patients money.

“It’s a common misperception that a 30% decrease in the cost of a several thousand dollar-a-month drug is going to automatically open all the doors to access,” said Dr. Sean Fahey, a rheumatologist in Mooresville, N.C., and chair of the insurance subcommittee of the ACR’s Committee on Rheumatologic Care. “Most of my patients who use biologics do so either through copay cards from the pharmaceutical industry or through Medicare and a secondary [payer] covering their out-of-pocket costs for the infusible biologics. This is clearly saving the system money, which is important no doubt, but unless it’s significantly less expensive, it actually might not change the patient’s out-of pocket [cost] all that much.”

The patient assistance programs from biologics manufacturers that offer copay assistance, access hotlines, and administration benefits could be in jeopardy with the rise of biosimilars. Since the programs are bundled into the average wholesale price of the drug, the savings offered by the reduced wholesale price of biosimilars may squeeze them out, Dr. Krant said.

“There’s going to be a lot of hue and cry from the patients who cannot self-administer or have problems with compliance because of copays in the first place,” he predicted.

Another factor that could affect how much biosimilars such as Inflectra will be used is the amount of rebates or discounts that payers receive directly from the pharmaceutical manufacturers.

“We know for the Medicaid population what the average sales prices are, but for private payers, we don’t know if they’re giving 2%, 5%, 18%; we have no idea what the data are. This could affect how much market share Inflectra gets,” said Dr. Fahey, who is also president of the North Carolina Rheumatology Association.

It may be awhile before Inflectra is available on the U.S. market. In a statement following the approval of Inflectra, Remicade-maker Janssen said the “patents for Remicade remain valid and enforceable until September 2018. A commercial launch of Celltrion’s infliximab-dyyb in advance of this date would be an infringement of our patents, and we intend to defend our intellectual property rights.”

Janssen notes that its patient support program for Remicade “continues to offer a copay card for patients with commercial insurance that reduces the patient out-of-pocket cost to no more than $5 per infusion. Eligible uninsured and underinsured patients may be able to access Remicade through the Johnson & Johnson Patient Assistance Foundation.”

Pfizer, which owns the rights to marketing Inflectra in the United States, did not respond directly to a question about whether it would have a payment assistance program for Inflectra. “While we cannot comment on specific commercialization strategies at this time, we are working to bring these important therapies to market in the U.S. as quickly as possible,” said Rachel Hooper, Director of Public Affairs, West, for Pfizer.

It seems likely that once Inflectra does come to the market, new starts will account for many patients who will use the drug because of the lack of information available about whether there is, or is not, significant risk of immunogenicity with switching or loss of efficacy, Dr. Fahey said. “What is less certain is whether the payers will try to force us to move people from the Remicade brand to the infliximab biosimilar, and what the potential consequences of that is going to be.”

Dr. Krant, Dr. Fahey, and Mr. Marmaras had no relevant disclosures.

[email protected]

Now that the Food and Drug Administration has approved Inflectra as the first biosimilar version of the anti–tumor necrosis factor-alpha agent Remicade, rheumatologists and patient advocacy groups are taking stock of how it may be used in practice, and what the future holds for biosimilar drugs, with so many questions still unanswered regarding price, substitution, and safety.

Joseph Riccio/Adirondack Health

Inflectra, approved in early April and given the generic name of infliximab-dyyb under the FDA’s nomenclature for biosimilar products, will have the same indications as Remicade. The agency extrapolated the clinical trial data that Inflectra’s South Korea–based manufacturer, Celltrion, submitted for rheumatoid arthritis and ankylosing spondylitis to all other indications for which Remicade is approved.

It’s currently unclear how the FDA will note which clinical data in Inflectra’s labeling come from Inflectra and which from Remicade, and the same concerns lie with future biosimilar approvals if their results are extrapolated to indications not tested to show biosimilarity in clinical trials.

Labeling questions

It’s concerning to rheumatologists and the patients who will be using them that biosimilars such as Inflectra are not subject to the same pivotal trial experience as the reference biologics on which they are based, according to Dr. Jonathan Krant, section chief of rheumatology for Adirondack Health Systems in Saranac Lake, N.Y., and medical director for CreakyJoints, a community of patients with arthritis and caregivers, and its larger parent nonprofit advocacy organization, the Global Healthy Living Foundation (GHLF).

While the unique regulatory requirements in the biosimilar approval pathway reduce development costs and could potentially make Inflectra’s average wholesale price 30% less than Remicade – as was the case when Inflectra was first on the market in Europe – it’s not known how reduced costs may affect the safety of biosimilars.

“It worries all of us that manufacturers may cut corners to manage the cost constraints imposed by managed care,” Dr. Krant said in an interview.

Given that U.S. rheumatologists don’t have experience with biosimilars, Dr. Krant is anticipating some push back. “I think some physicians are going to fight back and won’t want to prescribe them, even if mandated, because of concerns regarding patient safety,” he said.

In a written statement, Dr. Joan Von Feldt, president of the American College of Rheumatology, welcomed the potential benefits on access to care that cost-saving biosimilars may bring to the U.S. health care system, but also said that “the safety of our patients remains our highest priority. As such, we encourage the FDA to continue to apply distinct names for future biosimilars, and to maximize clarity in the labeling of biosimilars, specifically with respect to their interchangeable status and the origins (reference drug versus biosimilar) of clinical data upon which FDA approval is based.”

Inflectra met the FDA’s “very similar” criteria to be approved as a biosimilar by showing it has no clinically meaningful differences in terms of safety and effectiveness from Remicade, the agency said. According to FDA regulations, biosimilar products can have only minor differences in clinically inactive components and must have the same mechanism(s) of action (to the extent that it is known) and route(s) of administration, dosage form(s), and strength(s) as the reference product and can be approved only for the indication(s) and condition(s) of use that have been approved for the reference product.

However, it may not hold true that Inflectra will have the same efficacy and safety for all indications that Remicade had due to potential differences in the mechanism of action through which Remicade exerts its effect across indications, which in this case may apply to the indications for Crohn’s disease and ulcerative colitis.

Health Canada chose not to extrapolate the indications for Inflectra (known as Remsima in Canada) to Crohn’s disease and ulcerative colitis because of “observed differences in the level of afucosylation, Fc-gammaRIIIa receptor binding, and some in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) assays” that could not rule out the possibility that Inflectra and Remicade differ in their ability to induce ADCC. Unlike the other indications for Remicade, Health Canada said “ADCC cannot be ruled out as a mechanism of action in the inflammatory bowel diseases. This position is supported by the observation that certolizumab pegol, another anti-TNF [anti–tumor necrosis factor] that lacks the ability to induce ADCC, displays only marginal efficacy in Crohn’s patients, compared with other anti-TNFs, namely infliximab.”

Other organizations suggest that extrapolation of indications is only appropriate when it is benefiting the patient to the greatest extent possible.

“GHLF is okay with extrapolation of indication unless the mechanism of action for the therapy is either scientifically or therapeutically outdated,” Stephen Marmaras, state and national advocacy manager for the GHLF, said in an interview. “Patients are okay with extrapolating data in order to expedite the approval process as long as you are extrapolating to best in class therapy for a particular indication. What [the GHLF is] saying is we want biosimilars to be an improvement on what we have, not the lowest common denominator. We shouldn’t be extrapolating indications data from products that aren’t considered to be the best product for that indication.”

“If we’re just judging on expediting the approval process for indications that are not considered to be really treated well by this particular drug, you have to always assume that the insurance company is going to go with the lowest common denominator,” he added. “What that could lead to, from a slippery-slope perspective, is the chipping away of the use of cutting-edge therapies.”

Substitution concerns

Inflectra was not approved as interchangeable with Remicade or other infliximab biosimilars. The FDA has yet to define the regulatory requirements for interchangeability that are necessary to meet the requirements of the Biologics Price Competition and Innovation Act of 2009. That Act states that an approved biosimilar “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.”

A statement about implementation of the Act on the FDA website explains that for interchangeability, “a sponsor must demonstrate that the biosimilar product can be expected to produce the same clinical result as the reference product in any given patient and, for a biological product that is administered more than once, that the risk of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of maintaining the patient on the reference product.”

One of the biggest concerns that physicians have is that biosimilars will be substituted for the reference products without notification, Dr. Krant said. “State by state we’re looking at potential substitution rules which allow pharmacists to switch out these cheaper molecules for the reference product,” he said, and without timely notification, patients and rheumatologists won’t know whether it was the reference product or a biosimilar that was associated with an adverse event or loss of efficacy.

The ACR and patient advocacy organizations such as the GHLF are against forced switching of patients for nonmedical reasons. Patients’ and rheumatologists’ confidence in biosimilar safety will be key to their uptake and the overall expansion of access to biologics to more patients, Mr. Marmaras said.

Patient costs uncertain

Although rheumatologists hope that with biosimilars’ lower costs, access will expand, there is no guarantee it will do so by saving patients money.

“It’s a common misperception that a 30% decrease in the cost of a several thousand dollar-a-month drug is going to automatically open all the doors to access,” said Dr. Sean Fahey, a rheumatologist in Mooresville, N.C., and chair of the insurance subcommittee of the ACR’s Committee on Rheumatologic Care. “Most of my patients who use biologics do so either through copay cards from the pharmaceutical industry or through Medicare and a secondary [payer] covering their out-of-pocket costs for the infusible biologics. This is clearly saving the system money, which is important no doubt, but unless it’s significantly less expensive, it actually might not change the patient’s out-of pocket [cost] all that much.”

The patient assistance programs from biologics manufacturers that offer copay assistance, access hotlines, and administration benefits could be in jeopardy with the rise of biosimilars. Since the programs are bundled into the average wholesale price of the drug, the savings offered by the reduced wholesale price of biosimilars may squeeze them out, Dr. Krant said.

“There’s going to be a lot of hue and cry from the patients who cannot self-administer or have problems with compliance because of copays in the first place,” he predicted.

Another factor that could affect how much biosimilars such as Inflectra will be used is the amount of rebates or discounts that payers receive directly from the pharmaceutical manufacturers.

“We know for the Medicaid population what the average sales prices are, but for private payers, we don’t know if they’re giving 2%, 5%, 18%; we have no idea what the data are. This could affect how much market share Inflectra gets,” said Dr. Fahey, who is also president of the North Carolina Rheumatology Association.

It may be awhile before Inflectra is available on the U.S. market. In a statement following the approval of Inflectra, Remicade-maker Janssen said the “patents for Remicade remain valid and enforceable until September 2018. A commercial launch of Celltrion’s infliximab-dyyb in advance of this date would be an infringement of our patents, and we intend to defend our intellectual property rights.”

Janssen notes that its patient support program for Remicade “continues to offer a copay card for patients with commercial insurance that reduces the patient out-of-pocket cost to no more than $5 per infusion. Eligible uninsured and underinsured patients may be able to access Remicade through the Johnson & Johnson Patient Assistance Foundation.”

Pfizer, which owns the rights to marketing Inflectra in the United States, did not respond directly to a question about whether it would have a payment assistance program for Inflectra. “While we cannot comment on specific commercialization strategies at this time, we are working to bring these important therapies to market in the U.S. as quickly as possible,” said Rachel Hooper, Director of Public Affairs, West, for Pfizer.

It seems likely that once Inflectra does come to the market, new starts will account for many patients who will use the drug because of the lack of information available about whether there is, or is not, significant risk of immunogenicity with switching or loss of efficacy, Dr. Fahey said. “What is less certain is whether the payers will try to force us to move people from the Remicade brand to the infliximab biosimilar, and what the potential consequences of that is going to be.”

Dr. Krant, Dr. Fahey, and Mr. Marmaras had no relevant disclosures.

[email protected]

A biosimilar version of the anti–tumor necrosis factor–alpha agent Remicade has been approved by the Food and Drug Administration, making it the first biosimilar drug approved by the agency for inflammatory diseases and just the second biosimilar it has approved.

The agency said in its April 5 announcement that the biosimilar drug, to be marketed as Inflectra, will have the same indications as Remicade: moderately to severely active Crohn’s disease in patients aged 6 years and older who have had an inadequate response to conventional therapy; moderately to severely active ulcerative colitis that has inadequately responded to conventional therapy; moderately to severely active rheumatoid arthritis in combination with methotrexate; active ankylosing spondylitis; active psoriatic arthritis; and chronic, severe plaque psoriasis.

Courtesy Wikimedia Commons/ FitzColinGerald/Creative Commons License

The drug, given the generic name of infliximab-dyyb under the agency’s nomenclature for biosimilar products, earned its approval as a biosimilar by showing it has no clinically meaningful differences in terms of safety and effectiveness from Remicade. According to FDA regulations, biosimilar products can have only minor differences in clinically inactive components and must have the same mechanism(s) of action (to the extent that it is known) and route(s) of administration, dosage form(s), and strength(s) as the reference product; and can be approved only for the indication(s) and condition(s) of use that have been approved for the reference product.

Inflectra’s approval is only as a biosimilar, not as an interchangeable product. The agency has yet to define the regulatory requirements for interchangeability that are necessary to meet the requirements of the Biologics Price Competition and Innovation Act of 2009. That Act states that an approved biosimilar “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.” A statement about implementation of the Act on the FDA website explains that for interchangeability, “a sponsor must demonstrate that the biosimilar product can be expected to produce the same clinical result as the reference product in any given patient and, for a biological product that is administered more than once, that the risk of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of maintaining the patient on the reference product.”

Like Remicade, Inflectra will come with a boxed warning and a Medication Guide that describes important information about its uses and risks, which include serious infections (tuberculosis, bacterial sepsis, invasive fungal infections, and others), lymphoma and other malignancies, liver injury, blood problems, lupuslike syndrome, psoriasis, and in rare cases, nervous system disorders.

Inflectra is manufactured by Celltrion, based in South Korea, for Illinois-based Hospira. Inflectra’s label can be found here.

[email protected]

A biosimilar version of the anti–tumor necrosis factor–alpha agent Remicade has been approved by the Food and Drug Administration, making it the first biosimilar drug approved by the agency for inflammatory diseases and just the second biosimilar it has approved.

The agency said in its April 5 announcement that the biosimilar drug, to be marketed as Inflectra, will have the same indications as Remicade: moderately to severely active Crohn’s disease in patients aged 6 years and older who have had an inadequate response to conventional therapy; moderately to severely active ulcerative colitis that has inadequately responded to conventional therapy; moderately to severely active rheumatoid arthritis in combination with methotrexate; active ankylosing spondylitis; active psoriatic arthritis; and chronic, severe plaque psoriasis.

Courtesy Wikimedia Commons/ FitzColinGerald/Creative Commons License

The drug, given the generic name of infliximab-dyyb under the agency’s nomenclature for biosimilar products, earned its approval as a biosimilar by showing it has no clinically meaningful differences in terms of safety and effectiveness from Remicade. According to FDA regulations, biosimilar products can have only minor differences in clinically inactive components and must have the same mechanism(s) of action (to the extent that it is known) and route(s) of administration, dosage form(s), and strength(s) as the reference product; and can be approved only for the indication(s) and condition(s) of use that have been approved for the reference product.

Inflectra’s approval is only as a biosimilar, not as an interchangeable product. The agency has yet to define the regulatory requirements for interchangeability that are necessary to meet the requirements of the Biologics Price Competition and Innovation Act of 2009. That Act states that an approved biosimilar “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.” A statement about implementation of the Act on the FDA website explains that for interchangeability, “a sponsor must demonstrate that the biosimilar product can be expected to produce the same clinical result as the reference product in any given patient and, for a biological product that is administered more than once, that the risk of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of maintaining the patient on the reference product.”

Like Remicade, Inflectra will come with a boxed warning and a Medication Guide that describes important information about its uses and risks, which include serious infections (tuberculosis, bacterial sepsis, invasive fungal infections, and others), lymphoma and other malignancies, liver injury, blood problems, lupuslike syndrome, psoriasis, and in rare cases, nervous system disorders.

Inflectra is manufactured by Celltrion, based in South Korea, for Illinois-based Hospira. Inflectra’s label can be found here.

[email protected]

A biosimilar version of the anti–tumor necrosis factor–alpha agent Remicade has been approved by the Food and Drug Administration, making it the first biosimilar drug approved by the agency for inflammatory diseases and just the second biosimilar it has approved.

The agency said in its April 5 announcement that the biosimilar drug, to be marketed as Inflectra, will have the same indications as Remicade: moderately to severely active Crohn’s disease in patients aged 6 years and older who have had an inadequate response to conventional therapy; moderately to severely active ulcerative colitis that has inadequately responded to conventional therapy; moderately to severely active rheumatoid arthritis in combination with methotrexate; active ankylosing spondylitis; active psoriatic arthritis; and chronic, severe plaque psoriasis.

Courtesy Wikimedia Commons/ FitzColinGerald/Creative Commons License

The drug, given the generic name of infliximab-dyyb under the agency’s nomenclature for biosimilar products, earned its approval as a biosimilar by showing it has no clinically meaningful differences in terms of safety and effectiveness from Remicade. According to FDA regulations, biosimilar products can have only minor differences in clinically inactive components and must have the same mechanism(s) of action (to the extent that it is known) and route(s) of administration, dosage form(s), and strength(s) as the reference product; and can be approved only for the indication(s) and condition(s) of use that have been approved for the reference product.

Inflectra’s approval is only as a biosimilar, not as an interchangeable product. The agency has yet to define the regulatory requirements for interchangeability that are necessary to meet the requirements of the Biologics Price Competition and Innovation Act of 2009. That Act states that an approved biosimilar “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.” A statement about implementation of the Act on the FDA website explains that for interchangeability, “a sponsor must demonstrate that the biosimilar product can be expected to produce the same clinical result as the reference product in any given patient and, for a biological product that is administered more than once, that the risk of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of maintaining the patient on the reference product.”

Like Remicade, Inflectra will come with a boxed warning and a Medication Guide that describes important information about its uses and risks, which include serious infections (tuberculosis, bacterial sepsis, invasive fungal infections, and others), lymphoma and other malignancies, liver injury, blood problems, lupuslike syndrome, psoriasis, and in rare cases, nervous system disorders.

Inflectra is manufactured by Celltrion, based in South Korea, for Illinois-based Hospira. Inflectra’s label can be found here.

[email protected]

Progression to structural damage occurs slowly among patients with early axial spondyloarthritis and more often takes place in current smokers, HLAB27 carriers, and those with signs of inflammation on MRI, according to new observations from the French DESIR cohort study.

The findings help to establish risk factors for early progression of nonradiographic axial spondyloarthritis (nr-axSpA) to radiographic disease, said Dr. Maxime Dougados of the department of rheumatology at Cochin Hospital, Paris, and his colleagues (Arthritis Rheumatol. 2016 Mar 18. doi: 10.1002/art.39666).

The study involved 449 patients with recent-onset inflammatory back pain who were participating in the multicenter, longitudinal DESIR study and had x-rays available at baseline and 2-year follow-up.

A total of 16 (4.9%) out of 326 patients who did not fulfill the modified New York criteria (mNY) at baseline progressed from nonradiographic to radiographic axSpA over the 2-year study period.

Of the 123 patients who met the mNY criteria at baseline, 7 (5.7%) no longer met the criteria at follow-up.

Independent factors found to influence the odds of progressing to radiographic axSpA were smoking status (odds ratio, 3.3; 95% confidence interval, 1.0-11.5), HLAB27 positivity (OR, 12.6; 95% CI, 2.3-274), and the presence of inflammation at MRI in the sacroiliac joints (SIJs) at baseline (OR, 48.8; 95% CI, 9.3-904), a multivariate analysis showed.

However, when the authors defined radiographic progression as “a worsening of at least one grade in at least one SIJ,” HLAB27 positivity (OR, 1.68; 95% CI, 0.8-3.71, P = .02), MRI positivity (OR, 5.85; 95% CI, 2.38-15.37, P less than .001), and baseline structural damage at SIJs on pelvic x-rays (OR, 6.35; 95% CI, 2.14-18.88; P less than .001) were predictors of radiographic disease progression. Another analysis confirmed those as risk factors even when the definition of progression also required a final absolute grade of at least 2 in the worsened SIJs.

When the authors considered the change in total score (based on the mean of two readers), only HLAB27 positivity and baseline MRI positivity were highlighted as independent predictors of disease progression. In this analysis, HLAB27 positivity and inflammation on MRI had grading score increases of 0.41 (P = .014) and 1.03 (P less than .001), respectively.

Unlike other studies, the researchers did not see a clear relationship between abnormal C-reactive protein at baseline and radiographic progression.

The findings suggest that, in early SpA, “structural progression does exist but is quite small and observed in a small number of patients,” the study authors wrote.

The authors noted that their findings should be “interpreted with caution” because they were based on a small number of patients, and additional studies with a longer-follow-up period are needed to confirm the findings.

The DESIR cohort was sponsored by the Department de la recherché Clinique et du Development de l’Assistance Publique-Hopitaux de Paris. An unrestricted grant from Pfizer was allocated for the 10 years of follow-up.

Progression to structural damage occurs slowly among patients with early axial spondyloarthritis and more often takes place in current smokers, HLAB27 carriers, and those with signs of inflammation on MRI, according to new observations from the French DESIR cohort study.

The findings help to establish risk factors for early progression of nonradiographic axial spondyloarthritis (nr-axSpA) to radiographic disease, said Dr. Maxime Dougados of the department of rheumatology at Cochin Hospital, Paris, and his colleagues (Arthritis Rheumatol. 2016 Mar 18. doi: 10.1002/art.39666).

The study involved 449 patients with recent-onset inflammatory back pain who were participating in the multicenter, longitudinal DESIR study and had x-rays available at baseline and 2-year follow-up.

A total of 16 (4.9%) out of 326 patients who did not fulfill the modified New York criteria (mNY) at baseline progressed from nonradiographic to radiographic axSpA over the 2-year study period.

Of the 123 patients who met the mNY criteria at baseline, 7 (5.7%) no longer met the criteria at follow-up.

Independent factors found to influence the odds of progressing to radiographic axSpA were smoking status (odds ratio, 3.3; 95% confidence interval, 1.0-11.5), HLAB27 positivity (OR, 12.6; 95% CI, 2.3-274), and the presence of inflammation at MRI in the sacroiliac joints (SIJs) at baseline (OR, 48.8; 95% CI, 9.3-904), a multivariate analysis showed.

However, when the authors defined radiographic progression as “a worsening of at least one grade in at least one SIJ,” HLAB27 positivity (OR, 1.68; 95% CI, 0.8-3.71, P = .02), MRI positivity (OR, 5.85; 95% CI, 2.38-15.37, P less than .001), and baseline structural damage at SIJs on pelvic x-rays (OR, 6.35; 95% CI, 2.14-18.88; P less than .001) were predictors of radiographic disease progression. Another analysis confirmed those as risk factors even when the definition of progression also required a final absolute grade of at least 2 in the worsened SIJs.

When the authors considered the change in total score (based on the mean of two readers), only HLAB27 positivity and baseline MRI positivity were highlighted as independent predictors of disease progression. In this analysis, HLAB27 positivity and inflammation on MRI had grading score increases of 0.41 (P = .014) and 1.03 (P less than .001), respectively.

Unlike other studies, the researchers did not see a clear relationship between abnormal C-reactive protein at baseline and radiographic progression.

The findings suggest that, in early SpA, “structural progression does exist but is quite small and observed in a small number of patients,” the study authors wrote.

The authors noted that their findings should be “interpreted with caution” because they were based on a small number of patients, and additional studies with a longer-follow-up period are needed to confirm the findings.

The DESIR cohort was sponsored by the Department de la recherché Clinique et du Development de l’Assistance Publique-Hopitaux de Paris. An unrestricted grant from Pfizer was allocated for the 10 years of follow-up.

Progression to structural damage occurs slowly among patients with early axial spondyloarthritis and more often takes place in current smokers, HLAB27 carriers, and those with signs of inflammation on MRI, according to new observations from the French DESIR cohort study.

The findings help to establish risk factors for early progression of nonradiographic axial spondyloarthritis (nr-axSpA) to radiographic disease, said Dr. Maxime Dougados of the department of rheumatology at Cochin Hospital, Paris, and his colleagues (Arthritis Rheumatol. 2016 Mar 18. doi: 10.1002/art.39666).

The study involved 449 patients with recent-onset inflammatory back pain who were participating in the multicenter, longitudinal DESIR study and had x-rays available at baseline and 2-year follow-up.

A total of 16 (4.9%) out of 326 patients who did not fulfill the modified New York criteria (mNY) at baseline progressed from nonradiographic to radiographic axSpA over the 2-year study period.

Of the 123 patients who met the mNY criteria at baseline, 7 (5.7%) no longer met the criteria at follow-up.

Independent factors found to influence the odds of progressing to radiographic axSpA were smoking status (odds ratio, 3.3; 95% confidence interval, 1.0-11.5), HLAB27 positivity (OR, 12.6; 95% CI, 2.3-274), and the presence of inflammation at MRI in the sacroiliac joints (SIJs) at baseline (OR, 48.8; 95% CI, 9.3-904), a multivariate analysis showed.

However, when the authors defined radiographic progression as “a worsening of at least one grade in at least one SIJ,” HLAB27 positivity (OR, 1.68; 95% CI, 0.8-3.71, P = .02), MRI positivity (OR, 5.85; 95% CI, 2.38-15.37, P less than .001), and baseline structural damage at SIJs on pelvic x-rays (OR, 6.35; 95% CI, 2.14-18.88; P less than .001) were predictors of radiographic disease progression. Another analysis confirmed those as risk factors even when the definition of progression also required a final absolute grade of at least 2 in the worsened SIJs.

When the authors considered the change in total score (based on the mean of two readers), only HLAB27 positivity and baseline MRI positivity were highlighted as independent predictors of disease progression. In this analysis, HLAB27 positivity and inflammation on MRI had grading score increases of 0.41 (P = .014) and 1.03 (P less than .001), respectively.

Unlike other studies, the researchers did not see a clear relationship between abnormal C-reactive protein at baseline and radiographic progression.

The findings suggest that, in early SpA, “structural progression does exist but is quite small and observed in a small number of patients,” the study authors wrote.

The authors noted that their findings should be “interpreted with caution” because they were based on a small number of patients, and additional studies with a longer-follow-up period are needed to confirm the findings.

The DESIR cohort was sponsored by the Department de la recherché Clinique et du Development de l’Assistance Publique-Hopitaux de Paris. An unrestricted grant from Pfizer was allocated for the 10 years of follow-up.