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Conditional recommendations rule in new SARD-associated interstitial lung disease guidelines
SAN DIEGO – In the spring of 2024, the American College of Rheumatology is expected to release guidelines to help inform the screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs).
The guidelines, which were previewed during a session at the ACR’s annual meeting, will include 50 recommendations, 3 of which met criteria for a strong rating:
- For people with SARDs at increased risk of developing ILD, the authors strongly recommend against screening with surgical lung biopsy.
- For people with systemic sclerosis (SSc)-related ILD, the authors strongly recommend against glucocorticoids as a first-line ILD treatment.
- For people with SSc-related ILD progression despite an initial ILD treatment, the authors strongly recommend against using long-term glucocorticoids.
Elana J. Bernstein, MD, MSc, a rheumatologist who directs the Columbia/New York-Presbyterian Scleroderma Center, and Sindhu R. Johnson, MD, a rheumatologist who directs the Toronto Scleroderma Program at the University of Toronto, provided a sneak peek of the recommendations to attendees before anticipated publication in Arthritis & Rheumatology and Arthritis Care & Research. For now, guideline summaries for screening and monitoring and treatment are currently available, and three manuscripts are under peer review: one about screening and monitoring, one about treatment, and one about the patient panel that participated in the effort.
“ILD is a significant cause of morbidity and mortality in people with SARDs,” said Dr. Bernstein, who is co-first author of the guidelines. “People with systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren’s disease are at greatest risk of developing ILD.”
Pediatric patients with SARDs excluded
The guidelines’ population of interest was people 17 years of age and older who were diagnosed with SARDs with a high risk of ILD. Pediatric patients with SARDs were excluded from the endeavor, as were those with systemic lupus erythematosus, antineutrophil cytoplasmic antibody–associated vasculitis, sarcoidosis, ankylosing spondylitis, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features, and those with unclassifiable ILD.
In the realm of screening, the guideline authors conditionally recommend two screening tests for patients considered at increased risk of ILD: pulmonary function tests and high-resolution chest CT (HRCT). Pulmonary function tests should include spirometry, lung volumes, and diffusion capacity. “Office spirometry alone is insufficient,” said Dr. Johnson, who served as lead author of the guidelines. And while a HRCT scan is recommended, “some patients may present to the emergency room with acute onset shortness of breath, and they may receive a CT angiogram to screen for pulmonary embolism,” she said. “It’s important to note that CT angiograms are performed in incomplete inspiration to maximize pulmonary artery enhancement. This may produce atelectasis that may obscure or mimic ILD. As a result, CTA studies are often inadequate to screen for ILD.”
Once a patient is diagnosed with ILD, three tests are recommended for monitoring: pulmonary function testing (every 3-6 months the first year in patients with IIM and SSc, then less frequently once stable, and every 3-12 months in the first year in patients with RA, SjD, and MCTD, then less frequently once stable); ambulatory desaturation testing every 3-12 months; and HRCT as needed. Dr. Johnson noted that while that the screening of ILD lies within the realm of rheumatologists, “once a patient is diagnosed, we are encouraged to comanage these patients with pulmonologists,” she said. “Ambulatory desaturation testing is not an infrequent test in the hands of pulmonologists. This is where co-management can be helpful.” She characterized a 6-minute walk test with continuous oximetry as “insufficient and is not synonymous with ambulatory desaturation testing. Ambulatory desaturation testing includes up titration of oxygen if a patient desaturates.”
The guidelines conditionally recommend against using chest radiography, 6-minute walk test distance, ambulatory desaturation testing, and bronchoscopy for ILD screening, and there is a strong recommendation against surgical lung biopsy. “However, there are unique circumstances where these tests may be considered,” Dr. Johnson said. “For example, ambulatory desaturation testing may be helpful if a patient is unable to perform a pulmonary function test. Bronchoscopy may be used to rule out infection, sarcoidosis, lymphoma, or alveolar hemorrhage, and surgical lung biopsy may be considered if you’re trying to rule out a malignancy.”
Similarly, several tests are conditionally recommended against for the monitoring of ILD, including chest radiography, the 6-minute walk test distance, and bronchoscopy. “But there are unique circumstances where they may be considered,” she said. “The 6-minute walk test may be used if a patient is unable to perform a pulmonary function test or if they’re being assessed for lung transplantation. Bronchoscopy may be used to rule out infection or alveolar hemorrhage.”
Preferred treatment options described
First-line treatment recommendations for ILD were based on the best available published evidence, voting panel expertise, and patient preferences. For SSc, the preferred treatment options include mycophenolate (CellCept), tocilizumab (Actemra), or rituximab (Rituxan and biosimilars), while additional options include cyclophosphamide, nintedanib (Ofev), and azathioprine. For myositis, the preferred treatment options include mycophenolate, azathioprine, rituximab, or calcineurin inhibitors, while additional options include a Janus kinase (JAK) inhibitor or cyclophosphamide. For MCTD, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include tocilizumab or cyclophosphamide. For RA and Sjögren’s, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include cyclophosphamide. Dr. Johnson emphasized that there was low certainty evidence to recommend one treatment over another. “Many situations might lead a provider to choose a different option for ILD treatment, such as the presence of comorbidities or extra-pulmonary disease,” she said. “So, while our guidelines were focused on effectiveness for ILD, providers may choose therapies that will help ILD and other disease manifestations.”
The guidelines conditionally recommend a short course of glucocorticoids as a bridging therapy or for treatment of a flare of ILD in patients with myositis, MCTD, RA, and Sjögren’s. The panel strongly recommends against the use of glucocorticoids in patients with SSc due to the concern for inducing a scleroderma renal crisis. “While this may be common knowledge for rheumatologists, it may not be common knowledge for pulmonologists,” she said. “So here is an opportunity to educate our pulmonology colleagues in our consultation notes.”
The guidelines also include recommendations for progression of ILD, which was defined using the INBUILD trial criteria. Mycophenolate is conditionally recommended to be the first ILD treatment for all SARDs when progression occurs, if it wasn’t the first ILD treatment used. “If it was, then other medications that rheumatologists are used to can be considered as the next ILD treatment in the face of progression: rituximab, nintedanib, tocilizumab, and cyclophosphamide,” she said. The guidelines include a conditional recommendation against long-term glucocorticoid use in myositis, MCTD, RA, and Sjögren’s, plus a strong recommendation against long-term glucocorticoid use in SSc. Finally, there is a conditional recommendation of referral for lung transplant evaluation at the appropriate time at experienced centers.
Another group of recommendations has to do with cases of rapidly progressive ILD, which is characterized by rapid progression from no oxygen or a patient’s baseline oxygen requirement to a high oxygen requirement or intubation usually within days to weeks without a documented cause, such as infection or heart failure. “In cases of rapidly progressive ILD, which typically occurs in the setting of anti-MDA5 antibodies, there is a conditional recommendation for IV glucocorticoids plus two additional therapies: traditionally rituximab and mycophenolate,” Dr. Johnson said. “However, what may be new to some clinicians is combination IVIG [intravenous immunoglobulin] and a calcineurin inhibitor, notably tacrolimus,” she said. “This is the situation where experience at expert centers is influencing our guidelines in advance of data.”
A patient panel provided input
For the undertaking, a core team that included six rheumatologists; one pulmonologist; one thoracic radiologist; one expert on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology; and two literature review experts developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. The literature review team included 13 rheumatologists, 8 pulmonologists, and 3 methodologists. Finally, a 21-member patient panel was convened to share their values and preferences regarding screening, monitoring, and treatment of SARD-related ILD. Of these, Dr. Bernstein said that 4 were at risk for ILD and 17 had been diagnosed with ILD. Next, the literature review team conducted a systematic review and used the GRADE methodology to rate the available evidence as high, moderate, low, or very low. Then, a voting panel comprising 13 rheumatologists, 10 pulmonologists, 1 radiologist, and 3 patients from the patient panel cast votes for each PICO question and made final recommendations.
The review of evidence left the guidelines authors with 241 PICO questions, “which is a lot,” Dr. Bernstein said. “To put this in perspective, some guidelines address only 10 or 15 PICO questions. Fortunately, we had a dedicated group of experts who were up to the challenge.” Dr. Johnson emphasized that the forthcoming guidelines should not be used by insurers to mandate a specific order of prescribing. “Clinicians must retain the latitude to prescribe medications based on individual patient factors and preferences,” she said.
Dr. Bernstein disclosed that she is an adviser to, a consultant for, and has received grant or research support from Boehringer Ingelheim and has also received grant or research support from Kadmon and Pfizer. Dr. Johnson disclosed that she has received research support from the American College of Rheumatology to develop these guidelines. She has also been an investigator for trials sponsored by Bristol-Myers Squibb, Roche, and Boehringer Ingelheim and has mitigated these relevant conflicts of interest 1 year prior to the development of these guidelines, and will continue to do so for the foreseeable future.
SAN DIEGO – In the spring of 2024, the American College of Rheumatology is expected to release guidelines to help inform the screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs).
The guidelines, which were previewed during a session at the ACR’s annual meeting, will include 50 recommendations, 3 of which met criteria for a strong rating:
- For people with SARDs at increased risk of developing ILD, the authors strongly recommend against screening with surgical lung biopsy.
- For people with systemic sclerosis (SSc)-related ILD, the authors strongly recommend against glucocorticoids as a first-line ILD treatment.
- For people with SSc-related ILD progression despite an initial ILD treatment, the authors strongly recommend against using long-term glucocorticoids.
Elana J. Bernstein, MD, MSc, a rheumatologist who directs the Columbia/New York-Presbyterian Scleroderma Center, and Sindhu R. Johnson, MD, a rheumatologist who directs the Toronto Scleroderma Program at the University of Toronto, provided a sneak peek of the recommendations to attendees before anticipated publication in Arthritis & Rheumatology and Arthritis Care & Research. For now, guideline summaries for screening and monitoring and treatment are currently available, and three manuscripts are under peer review: one about screening and monitoring, one about treatment, and one about the patient panel that participated in the effort.
“ILD is a significant cause of morbidity and mortality in people with SARDs,” said Dr. Bernstein, who is co-first author of the guidelines. “People with systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren’s disease are at greatest risk of developing ILD.”
Pediatric patients with SARDs excluded
The guidelines’ population of interest was people 17 years of age and older who were diagnosed with SARDs with a high risk of ILD. Pediatric patients with SARDs were excluded from the endeavor, as were those with systemic lupus erythematosus, antineutrophil cytoplasmic antibody–associated vasculitis, sarcoidosis, ankylosing spondylitis, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features, and those with unclassifiable ILD.
In the realm of screening, the guideline authors conditionally recommend two screening tests for patients considered at increased risk of ILD: pulmonary function tests and high-resolution chest CT (HRCT). Pulmonary function tests should include spirometry, lung volumes, and diffusion capacity. “Office spirometry alone is insufficient,” said Dr. Johnson, who served as lead author of the guidelines. And while a HRCT scan is recommended, “some patients may present to the emergency room with acute onset shortness of breath, and they may receive a CT angiogram to screen for pulmonary embolism,” she said. “It’s important to note that CT angiograms are performed in incomplete inspiration to maximize pulmonary artery enhancement. This may produce atelectasis that may obscure or mimic ILD. As a result, CTA studies are often inadequate to screen for ILD.”
Once a patient is diagnosed with ILD, three tests are recommended for monitoring: pulmonary function testing (every 3-6 months the first year in patients with IIM and SSc, then less frequently once stable, and every 3-12 months in the first year in patients with RA, SjD, and MCTD, then less frequently once stable); ambulatory desaturation testing every 3-12 months; and HRCT as needed. Dr. Johnson noted that while that the screening of ILD lies within the realm of rheumatologists, “once a patient is diagnosed, we are encouraged to comanage these patients with pulmonologists,” she said. “Ambulatory desaturation testing is not an infrequent test in the hands of pulmonologists. This is where co-management can be helpful.” She characterized a 6-minute walk test with continuous oximetry as “insufficient and is not synonymous with ambulatory desaturation testing. Ambulatory desaturation testing includes up titration of oxygen if a patient desaturates.”
The guidelines conditionally recommend against using chest radiography, 6-minute walk test distance, ambulatory desaturation testing, and bronchoscopy for ILD screening, and there is a strong recommendation against surgical lung biopsy. “However, there are unique circumstances where these tests may be considered,” Dr. Johnson said. “For example, ambulatory desaturation testing may be helpful if a patient is unable to perform a pulmonary function test. Bronchoscopy may be used to rule out infection, sarcoidosis, lymphoma, or alveolar hemorrhage, and surgical lung biopsy may be considered if you’re trying to rule out a malignancy.”
Similarly, several tests are conditionally recommended against for the monitoring of ILD, including chest radiography, the 6-minute walk test distance, and bronchoscopy. “But there are unique circumstances where they may be considered,” she said. “The 6-minute walk test may be used if a patient is unable to perform a pulmonary function test or if they’re being assessed for lung transplantation. Bronchoscopy may be used to rule out infection or alveolar hemorrhage.”
Preferred treatment options described
First-line treatment recommendations for ILD were based on the best available published evidence, voting panel expertise, and patient preferences. For SSc, the preferred treatment options include mycophenolate (CellCept), tocilizumab (Actemra), or rituximab (Rituxan and biosimilars), while additional options include cyclophosphamide, nintedanib (Ofev), and azathioprine. For myositis, the preferred treatment options include mycophenolate, azathioprine, rituximab, or calcineurin inhibitors, while additional options include a Janus kinase (JAK) inhibitor or cyclophosphamide. For MCTD, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include tocilizumab or cyclophosphamide. For RA and Sjögren’s, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include cyclophosphamide. Dr. Johnson emphasized that there was low certainty evidence to recommend one treatment over another. “Many situations might lead a provider to choose a different option for ILD treatment, such as the presence of comorbidities or extra-pulmonary disease,” she said. “So, while our guidelines were focused on effectiveness for ILD, providers may choose therapies that will help ILD and other disease manifestations.”
The guidelines conditionally recommend a short course of glucocorticoids as a bridging therapy or for treatment of a flare of ILD in patients with myositis, MCTD, RA, and Sjögren’s. The panel strongly recommends against the use of glucocorticoids in patients with SSc due to the concern for inducing a scleroderma renal crisis. “While this may be common knowledge for rheumatologists, it may not be common knowledge for pulmonologists,” she said. “So here is an opportunity to educate our pulmonology colleagues in our consultation notes.”
The guidelines also include recommendations for progression of ILD, which was defined using the INBUILD trial criteria. Mycophenolate is conditionally recommended to be the first ILD treatment for all SARDs when progression occurs, if it wasn’t the first ILD treatment used. “If it was, then other medications that rheumatologists are used to can be considered as the next ILD treatment in the face of progression: rituximab, nintedanib, tocilizumab, and cyclophosphamide,” she said. The guidelines include a conditional recommendation against long-term glucocorticoid use in myositis, MCTD, RA, and Sjögren’s, plus a strong recommendation against long-term glucocorticoid use in SSc. Finally, there is a conditional recommendation of referral for lung transplant evaluation at the appropriate time at experienced centers.
Another group of recommendations has to do with cases of rapidly progressive ILD, which is characterized by rapid progression from no oxygen or a patient’s baseline oxygen requirement to a high oxygen requirement or intubation usually within days to weeks without a documented cause, such as infection or heart failure. “In cases of rapidly progressive ILD, which typically occurs in the setting of anti-MDA5 antibodies, there is a conditional recommendation for IV glucocorticoids plus two additional therapies: traditionally rituximab and mycophenolate,” Dr. Johnson said. “However, what may be new to some clinicians is combination IVIG [intravenous immunoglobulin] and a calcineurin inhibitor, notably tacrolimus,” she said. “This is the situation where experience at expert centers is influencing our guidelines in advance of data.”
A patient panel provided input
For the undertaking, a core team that included six rheumatologists; one pulmonologist; one thoracic radiologist; one expert on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology; and two literature review experts developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. The literature review team included 13 rheumatologists, 8 pulmonologists, and 3 methodologists. Finally, a 21-member patient panel was convened to share their values and preferences regarding screening, monitoring, and treatment of SARD-related ILD. Of these, Dr. Bernstein said that 4 were at risk for ILD and 17 had been diagnosed with ILD. Next, the literature review team conducted a systematic review and used the GRADE methodology to rate the available evidence as high, moderate, low, or very low. Then, a voting panel comprising 13 rheumatologists, 10 pulmonologists, 1 radiologist, and 3 patients from the patient panel cast votes for each PICO question and made final recommendations.
The review of evidence left the guidelines authors with 241 PICO questions, “which is a lot,” Dr. Bernstein said. “To put this in perspective, some guidelines address only 10 or 15 PICO questions. Fortunately, we had a dedicated group of experts who were up to the challenge.” Dr. Johnson emphasized that the forthcoming guidelines should not be used by insurers to mandate a specific order of prescribing. “Clinicians must retain the latitude to prescribe medications based on individual patient factors and preferences,” she said.
Dr. Bernstein disclosed that she is an adviser to, a consultant for, and has received grant or research support from Boehringer Ingelheim and has also received grant or research support from Kadmon and Pfizer. Dr. Johnson disclosed that she has received research support from the American College of Rheumatology to develop these guidelines. She has also been an investigator for trials sponsored by Bristol-Myers Squibb, Roche, and Boehringer Ingelheim and has mitigated these relevant conflicts of interest 1 year prior to the development of these guidelines, and will continue to do so for the foreseeable future.
SAN DIEGO – In the spring of 2024, the American College of Rheumatology is expected to release guidelines to help inform the screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs).
The guidelines, which were previewed during a session at the ACR’s annual meeting, will include 50 recommendations, 3 of which met criteria for a strong rating:
- For people with SARDs at increased risk of developing ILD, the authors strongly recommend against screening with surgical lung biopsy.
- For people with systemic sclerosis (SSc)-related ILD, the authors strongly recommend against glucocorticoids as a first-line ILD treatment.
- For people with SSc-related ILD progression despite an initial ILD treatment, the authors strongly recommend against using long-term glucocorticoids.
Elana J. Bernstein, MD, MSc, a rheumatologist who directs the Columbia/New York-Presbyterian Scleroderma Center, and Sindhu R. Johnson, MD, a rheumatologist who directs the Toronto Scleroderma Program at the University of Toronto, provided a sneak peek of the recommendations to attendees before anticipated publication in Arthritis & Rheumatology and Arthritis Care & Research. For now, guideline summaries for screening and monitoring and treatment are currently available, and three manuscripts are under peer review: one about screening and monitoring, one about treatment, and one about the patient panel that participated in the effort.
“ILD is a significant cause of morbidity and mortality in people with SARDs,” said Dr. Bernstein, who is co-first author of the guidelines. “People with systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren’s disease are at greatest risk of developing ILD.”
Pediatric patients with SARDs excluded
The guidelines’ population of interest was people 17 years of age and older who were diagnosed with SARDs with a high risk of ILD. Pediatric patients with SARDs were excluded from the endeavor, as were those with systemic lupus erythematosus, antineutrophil cytoplasmic antibody–associated vasculitis, sarcoidosis, ankylosing spondylitis, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features, and those with unclassifiable ILD.
In the realm of screening, the guideline authors conditionally recommend two screening tests for patients considered at increased risk of ILD: pulmonary function tests and high-resolution chest CT (HRCT). Pulmonary function tests should include spirometry, lung volumes, and diffusion capacity. “Office spirometry alone is insufficient,” said Dr. Johnson, who served as lead author of the guidelines. And while a HRCT scan is recommended, “some patients may present to the emergency room with acute onset shortness of breath, and they may receive a CT angiogram to screen for pulmonary embolism,” she said. “It’s important to note that CT angiograms are performed in incomplete inspiration to maximize pulmonary artery enhancement. This may produce atelectasis that may obscure or mimic ILD. As a result, CTA studies are often inadequate to screen for ILD.”
Once a patient is diagnosed with ILD, three tests are recommended for monitoring: pulmonary function testing (every 3-6 months the first year in patients with IIM and SSc, then less frequently once stable, and every 3-12 months in the first year in patients with RA, SjD, and MCTD, then less frequently once stable); ambulatory desaturation testing every 3-12 months; and HRCT as needed. Dr. Johnson noted that while that the screening of ILD lies within the realm of rheumatologists, “once a patient is diagnosed, we are encouraged to comanage these patients with pulmonologists,” she said. “Ambulatory desaturation testing is not an infrequent test in the hands of pulmonologists. This is where co-management can be helpful.” She characterized a 6-minute walk test with continuous oximetry as “insufficient and is not synonymous with ambulatory desaturation testing. Ambulatory desaturation testing includes up titration of oxygen if a patient desaturates.”
The guidelines conditionally recommend against using chest radiography, 6-minute walk test distance, ambulatory desaturation testing, and bronchoscopy for ILD screening, and there is a strong recommendation against surgical lung biopsy. “However, there are unique circumstances where these tests may be considered,” Dr. Johnson said. “For example, ambulatory desaturation testing may be helpful if a patient is unable to perform a pulmonary function test. Bronchoscopy may be used to rule out infection, sarcoidosis, lymphoma, or alveolar hemorrhage, and surgical lung biopsy may be considered if you’re trying to rule out a malignancy.”
Similarly, several tests are conditionally recommended against for the monitoring of ILD, including chest radiography, the 6-minute walk test distance, and bronchoscopy. “But there are unique circumstances where they may be considered,” she said. “The 6-minute walk test may be used if a patient is unable to perform a pulmonary function test or if they’re being assessed for lung transplantation. Bronchoscopy may be used to rule out infection or alveolar hemorrhage.”
Preferred treatment options described
First-line treatment recommendations for ILD were based on the best available published evidence, voting panel expertise, and patient preferences. For SSc, the preferred treatment options include mycophenolate (CellCept), tocilizumab (Actemra), or rituximab (Rituxan and biosimilars), while additional options include cyclophosphamide, nintedanib (Ofev), and azathioprine. For myositis, the preferred treatment options include mycophenolate, azathioprine, rituximab, or calcineurin inhibitors, while additional options include a Janus kinase (JAK) inhibitor or cyclophosphamide. For MCTD, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include tocilizumab or cyclophosphamide. For RA and Sjögren’s, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include cyclophosphamide. Dr. Johnson emphasized that there was low certainty evidence to recommend one treatment over another. “Many situations might lead a provider to choose a different option for ILD treatment, such as the presence of comorbidities or extra-pulmonary disease,” she said. “So, while our guidelines were focused on effectiveness for ILD, providers may choose therapies that will help ILD and other disease manifestations.”
The guidelines conditionally recommend a short course of glucocorticoids as a bridging therapy or for treatment of a flare of ILD in patients with myositis, MCTD, RA, and Sjögren’s. The panel strongly recommends against the use of glucocorticoids in patients with SSc due to the concern for inducing a scleroderma renal crisis. “While this may be common knowledge for rheumatologists, it may not be common knowledge for pulmonologists,” she said. “So here is an opportunity to educate our pulmonology colleagues in our consultation notes.”
The guidelines also include recommendations for progression of ILD, which was defined using the INBUILD trial criteria. Mycophenolate is conditionally recommended to be the first ILD treatment for all SARDs when progression occurs, if it wasn’t the first ILD treatment used. “If it was, then other medications that rheumatologists are used to can be considered as the next ILD treatment in the face of progression: rituximab, nintedanib, tocilizumab, and cyclophosphamide,” she said. The guidelines include a conditional recommendation against long-term glucocorticoid use in myositis, MCTD, RA, and Sjögren’s, plus a strong recommendation against long-term glucocorticoid use in SSc. Finally, there is a conditional recommendation of referral for lung transplant evaluation at the appropriate time at experienced centers.
Another group of recommendations has to do with cases of rapidly progressive ILD, which is characterized by rapid progression from no oxygen or a patient’s baseline oxygen requirement to a high oxygen requirement or intubation usually within days to weeks without a documented cause, such as infection or heart failure. “In cases of rapidly progressive ILD, which typically occurs in the setting of anti-MDA5 antibodies, there is a conditional recommendation for IV glucocorticoids plus two additional therapies: traditionally rituximab and mycophenolate,” Dr. Johnson said. “However, what may be new to some clinicians is combination IVIG [intravenous immunoglobulin] and a calcineurin inhibitor, notably tacrolimus,” she said. “This is the situation where experience at expert centers is influencing our guidelines in advance of data.”
A patient panel provided input
For the undertaking, a core team that included six rheumatologists; one pulmonologist; one thoracic radiologist; one expert on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology; and two literature review experts developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. The literature review team included 13 rheumatologists, 8 pulmonologists, and 3 methodologists. Finally, a 21-member patient panel was convened to share their values and preferences regarding screening, monitoring, and treatment of SARD-related ILD. Of these, Dr. Bernstein said that 4 were at risk for ILD and 17 had been diagnosed with ILD. Next, the literature review team conducted a systematic review and used the GRADE methodology to rate the available evidence as high, moderate, low, or very low. Then, a voting panel comprising 13 rheumatologists, 10 pulmonologists, 1 radiologist, and 3 patients from the patient panel cast votes for each PICO question and made final recommendations.
The review of evidence left the guidelines authors with 241 PICO questions, “which is a lot,” Dr. Bernstein said. “To put this in perspective, some guidelines address only 10 or 15 PICO questions. Fortunately, we had a dedicated group of experts who were up to the challenge.” Dr. Johnson emphasized that the forthcoming guidelines should not be used by insurers to mandate a specific order of prescribing. “Clinicians must retain the latitude to prescribe medications based on individual patient factors and preferences,” she said.
Dr. Bernstein disclosed that she is an adviser to, a consultant for, and has received grant or research support from Boehringer Ingelheim and has also received grant or research support from Kadmon and Pfizer. Dr. Johnson disclosed that she has received research support from the American College of Rheumatology to develop these guidelines. She has also been an investigator for trials sponsored by Bristol-Myers Squibb, Roche, and Boehringer Ingelheim and has mitigated these relevant conflicts of interest 1 year prior to the development of these guidelines, and will continue to do so for the foreseeable future.
AT ACR 2023
Abatacept reduced rates of progression to RA, phase 2b trial finds
SAN DIEGO – The use of abatacept (Orencia) in individuals at risk of developing rheumatoid arthritis is feasible, results from a proof-of-concept, phase 2b study showed.
The findings are encouraging because data from at-risk cohorts have reported rates of progression to RA in excess of 50% over 24 months, Andrew Cope, MBBS, PhD, head of the Center for Rheumatic Diseases at King’s College London, said during an abstract session at the annual meeting of the American College of Rheumatology. “If we’re going to do interception trials, we need to make sure that the risk-benefit is about right, and we also need to have enough events in the placebo arm against which to compare any impact of a drug,” he said.
For the randomized, placebo-controlled study known as the Arthritis Prevention in the Pre-clinical Phase of RA with Abatacept (APIPPRA) trial, Dr. Cope and colleagues at 28 sites in the United Kingdom and 3 in the Netherlands set out to evaluate the feasibility, efficacy, and acceptability of abatacept therapy in subjects at high risk of developing RA and to characterize the effects of T-cell costimulation modulation on the evaluation of immune and inflammatory responses associated with anti–citrullinated protein antibody (ACPA) prior to, during, and after therapy. They enrolled male and female individuals aged 18 and older with arthralgia, considered to be inflammatory in nature, and who were either ACPA and rheumatoid factor (RF) positive, or had high-titer ACPA. The researchers excluded individuals with clinically apparent arthritis, or a history of inflammatory arthritis as assessed by a rheumatologist, as well as those with a history or current use of conventional or targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs), or oral or parenteral use of corticosteroids. They also excluded people with comorbidities requiring treatment with immunosuppressive or immune-modulating therapy, those who had received a live vaccine in the prior 3 months, as well as those who were pregnant or breastfeeding.
Study participants were randomized 1:1 to receive 52 weekly subcutaneous injections of placebo or 125 mg abatacept and were followed for another 52 weeks. The primary endpoint was time to development of clinically apparent arthritis in at least three joints, or to fulfillment of the ACR/European Alliance of Associations for Rheumatology 2010 criteria for RA, whichever comes first, during 24 months of follow-up, with joint synovitis confirmed by ultrasound.
Dr. Cope reported results from 103 patients in the placebo arm and 110 patients in the abatacept arm. Their mean age was 49 years and 77% were female. At baseline, 73% of study participants had a power Doppler score of 0, which suggests minimal levels of active subclinical synovitis in a substantial proportion of this at-risk trial population. At 52 weeks, the researchers observed 30 events in the placebo arm (29%) and 7 in the abatacept arm (6%), while at 104 weeks, there were 38 events in the placebo arm (37%) and 27 in the abatacept arm (25%). This reflected a difference in mean arthritis-free survival time between arms of 99.2 days in favor of abatacept (P = .002).
Prespecified exploratory analysis showed that individuals with high levels of ACPA or who had an extended autoantibody profile at baseline were more likely to remain arthritis-free after abatacept therapy. “So, we’re seeing a hint here that there is an abatacept-sensitive population,” Dr. Cope said.
There were 7 serious adverse events in the abatacept group and 11 in the placebo group, including 2 deaths, 1 in each arm. None of the deaths were attributable to the study drug.
In other findings during the treatment phase, subjects in the abatacept arm, when compared to those in the placebo arm, had reduced levels of anxiety on the Hospital Anxiety Depression Scale; reduced fatigue, improved physical and emotional well-being, and improved functional well-being on the Functional Assessment of Chronic Illness Therapy-Fatigue measure; reduced sleep problems on the Symptoms in Persons at Risk of Rheumatoid Arthritis questionnaire; positive impact on work instability on the RA Work Instability Scale, and a positive impact on illness beliefs.
Based on the study findings, Dr. Cope concluded that clinical trials of RA interception are feasible, and that the rates of progression to RA are consistent with cohorts in other studies. “Abatacept reduced rates of progression to RA,” he said. “We also have data to suggest that the drug reduced subclinical inflammation as defined by ultrasound.”
One of the session moderators, Jon T. Giles, MD, MPH, associate professor of medicine at Columbia University, New York, asked Dr. Cope how he and his colleagues assessed the acceptability of abatacept. “Drug adherence is quite a good way to assess that, and we set the adherence level stringently at about 90%,” Dr. Cope said. “The nonadherence was about 26%. Getting people who don’t have disease to inject [the drug] weekly is not a trivial thing.”
Bristol-Myers Squibb funded the study. Dr. Cope disclosed that he has received grant support, consulting, and/or speakers bureau fees from GlaxoSmithKline, AbbVie, Janssen, Bristol-Myers Squibb, UCB, Galapagos, and Lilly. Many coauthors of the APIPPRA trial had financial relationships with multiple pharmaceutical companies, including Bristol-Myers Squibb. Dr. Giles disclosed that he is a consultant for AbbVie, Gilead, Lilly, Novartis, and Pfizer.
SAN DIEGO – The use of abatacept (Orencia) in individuals at risk of developing rheumatoid arthritis is feasible, results from a proof-of-concept, phase 2b study showed.
The findings are encouraging because data from at-risk cohorts have reported rates of progression to RA in excess of 50% over 24 months, Andrew Cope, MBBS, PhD, head of the Center for Rheumatic Diseases at King’s College London, said during an abstract session at the annual meeting of the American College of Rheumatology. “If we’re going to do interception trials, we need to make sure that the risk-benefit is about right, and we also need to have enough events in the placebo arm against which to compare any impact of a drug,” he said.
For the randomized, placebo-controlled study known as the Arthritis Prevention in the Pre-clinical Phase of RA with Abatacept (APIPPRA) trial, Dr. Cope and colleagues at 28 sites in the United Kingdom and 3 in the Netherlands set out to evaluate the feasibility, efficacy, and acceptability of abatacept therapy in subjects at high risk of developing RA and to characterize the effects of T-cell costimulation modulation on the evaluation of immune and inflammatory responses associated with anti–citrullinated protein antibody (ACPA) prior to, during, and after therapy. They enrolled male and female individuals aged 18 and older with arthralgia, considered to be inflammatory in nature, and who were either ACPA and rheumatoid factor (RF) positive, or had high-titer ACPA. The researchers excluded individuals with clinically apparent arthritis, or a history of inflammatory arthritis as assessed by a rheumatologist, as well as those with a history or current use of conventional or targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs), or oral or parenteral use of corticosteroids. They also excluded people with comorbidities requiring treatment with immunosuppressive or immune-modulating therapy, those who had received a live vaccine in the prior 3 months, as well as those who were pregnant or breastfeeding.
Study participants were randomized 1:1 to receive 52 weekly subcutaneous injections of placebo or 125 mg abatacept and were followed for another 52 weeks. The primary endpoint was time to development of clinically apparent arthritis in at least three joints, or to fulfillment of the ACR/European Alliance of Associations for Rheumatology 2010 criteria for RA, whichever comes first, during 24 months of follow-up, with joint synovitis confirmed by ultrasound.
Dr. Cope reported results from 103 patients in the placebo arm and 110 patients in the abatacept arm. Their mean age was 49 years and 77% were female. At baseline, 73% of study participants had a power Doppler score of 0, which suggests minimal levels of active subclinical synovitis in a substantial proportion of this at-risk trial population. At 52 weeks, the researchers observed 30 events in the placebo arm (29%) and 7 in the abatacept arm (6%), while at 104 weeks, there were 38 events in the placebo arm (37%) and 27 in the abatacept arm (25%). This reflected a difference in mean arthritis-free survival time between arms of 99.2 days in favor of abatacept (P = .002).
Prespecified exploratory analysis showed that individuals with high levels of ACPA or who had an extended autoantibody profile at baseline were more likely to remain arthritis-free after abatacept therapy. “So, we’re seeing a hint here that there is an abatacept-sensitive population,” Dr. Cope said.
There were 7 serious adverse events in the abatacept group and 11 in the placebo group, including 2 deaths, 1 in each arm. None of the deaths were attributable to the study drug.
In other findings during the treatment phase, subjects in the abatacept arm, when compared to those in the placebo arm, had reduced levels of anxiety on the Hospital Anxiety Depression Scale; reduced fatigue, improved physical and emotional well-being, and improved functional well-being on the Functional Assessment of Chronic Illness Therapy-Fatigue measure; reduced sleep problems on the Symptoms in Persons at Risk of Rheumatoid Arthritis questionnaire; positive impact on work instability on the RA Work Instability Scale, and a positive impact on illness beliefs.
Based on the study findings, Dr. Cope concluded that clinical trials of RA interception are feasible, and that the rates of progression to RA are consistent with cohorts in other studies. “Abatacept reduced rates of progression to RA,” he said. “We also have data to suggest that the drug reduced subclinical inflammation as defined by ultrasound.”
One of the session moderators, Jon T. Giles, MD, MPH, associate professor of medicine at Columbia University, New York, asked Dr. Cope how he and his colleagues assessed the acceptability of abatacept. “Drug adherence is quite a good way to assess that, and we set the adherence level stringently at about 90%,” Dr. Cope said. “The nonadherence was about 26%. Getting people who don’t have disease to inject [the drug] weekly is not a trivial thing.”
Bristol-Myers Squibb funded the study. Dr. Cope disclosed that he has received grant support, consulting, and/or speakers bureau fees from GlaxoSmithKline, AbbVie, Janssen, Bristol-Myers Squibb, UCB, Galapagos, and Lilly. Many coauthors of the APIPPRA trial had financial relationships with multiple pharmaceutical companies, including Bristol-Myers Squibb. Dr. Giles disclosed that he is a consultant for AbbVie, Gilead, Lilly, Novartis, and Pfizer.
SAN DIEGO – The use of abatacept (Orencia) in individuals at risk of developing rheumatoid arthritis is feasible, results from a proof-of-concept, phase 2b study showed.
The findings are encouraging because data from at-risk cohorts have reported rates of progression to RA in excess of 50% over 24 months, Andrew Cope, MBBS, PhD, head of the Center for Rheumatic Diseases at King’s College London, said during an abstract session at the annual meeting of the American College of Rheumatology. “If we’re going to do interception trials, we need to make sure that the risk-benefit is about right, and we also need to have enough events in the placebo arm against which to compare any impact of a drug,” he said.
For the randomized, placebo-controlled study known as the Arthritis Prevention in the Pre-clinical Phase of RA with Abatacept (APIPPRA) trial, Dr. Cope and colleagues at 28 sites in the United Kingdom and 3 in the Netherlands set out to evaluate the feasibility, efficacy, and acceptability of abatacept therapy in subjects at high risk of developing RA and to characterize the effects of T-cell costimulation modulation on the evaluation of immune and inflammatory responses associated with anti–citrullinated protein antibody (ACPA) prior to, during, and after therapy. They enrolled male and female individuals aged 18 and older with arthralgia, considered to be inflammatory in nature, and who were either ACPA and rheumatoid factor (RF) positive, or had high-titer ACPA. The researchers excluded individuals with clinically apparent arthritis, or a history of inflammatory arthritis as assessed by a rheumatologist, as well as those with a history or current use of conventional or targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs), or oral or parenteral use of corticosteroids. They also excluded people with comorbidities requiring treatment with immunosuppressive or immune-modulating therapy, those who had received a live vaccine in the prior 3 months, as well as those who were pregnant or breastfeeding.
Study participants were randomized 1:1 to receive 52 weekly subcutaneous injections of placebo or 125 mg abatacept and were followed for another 52 weeks. The primary endpoint was time to development of clinically apparent arthritis in at least three joints, or to fulfillment of the ACR/European Alliance of Associations for Rheumatology 2010 criteria for RA, whichever comes first, during 24 months of follow-up, with joint synovitis confirmed by ultrasound.
Dr. Cope reported results from 103 patients in the placebo arm and 110 patients in the abatacept arm. Their mean age was 49 years and 77% were female. At baseline, 73% of study participants had a power Doppler score of 0, which suggests minimal levels of active subclinical synovitis in a substantial proportion of this at-risk trial population. At 52 weeks, the researchers observed 30 events in the placebo arm (29%) and 7 in the abatacept arm (6%), while at 104 weeks, there were 38 events in the placebo arm (37%) and 27 in the abatacept arm (25%). This reflected a difference in mean arthritis-free survival time between arms of 99.2 days in favor of abatacept (P = .002).
Prespecified exploratory analysis showed that individuals with high levels of ACPA or who had an extended autoantibody profile at baseline were more likely to remain arthritis-free after abatacept therapy. “So, we’re seeing a hint here that there is an abatacept-sensitive population,” Dr. Cope said.
There were 7 serious adverse events in the abatacept group and 11 in the placebo group, including 2 deaths, 1 in each arm. None of the deaths were attributable to the study drug.
In other findings during the treatment phase, subjects in the abatacept arm, when compared to those in the placebo arm, had reduced levels of anxiety on the Hospital Anxiety Depression Scale; reduced fatigue, improved physical and emotional well-being, and improved functional well-being on the Functional Assessment of Chronic Illness Therapy-Fatigue measure; reduced sleep problems on the Symptoms in Persons at Risk of Rheumatoid Arthritis questionnaire; positive impact on work instability on the RA Work Instability Scale, and a positive impact on illness beliefs.
Based on the study findings, Dr. Cope concluded that clinical trials of RA interception are feasible, and that the rates of progression to RA are consistent with cohorts in other studies. “Abatacept reduced rates of progression to RA,” he said. “We also have data to suggest that the drug reduced subclinical inflammation as defined by ultrasound.”
One of the session moderators, Jon T. Giles, MD, MPH, associate professor of medicine at Columbia University, New York, asked Dr. Cope how he and his colleagues assessed the acceptability of abatacept. “Drug adherence is quite a good way to assess that, and we set the adherence level stringently at about 90%,” Dr. Cope said. “The nonadherence was about 26%. Getting people who don’t have disease to inject [the drug] weekly is not a trivial thing.”
Bristol-Myers Squibb funded the study. Dr. Cope disclosed that he has received grant support, consulting, and/or speakers bureau fees from GlaxoSmithKline, AbbVie, Janssen, Bristol-Myers Squibb, UCB, Galapagos, and Lilly. Many coauthors of the APIPPRA trial had financial relationships with multiple pharmaceutical companies, including Bristol-Myers Squibb. Dr. Giles disclosed that he is a consultant for AbbVie, Gilead, Lilly, Novartis, and Pfizer.
AT ACR 2023
Risks quantified in medically optimized pregnancy with lupus
SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.
Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.
While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.
Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”
Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.
Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.
Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.
“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.
In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.
Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.
These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.
The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”
Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.
“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”
A version of this article appeared on Medscape.com.
SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.
Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.
While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.
Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”
Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.
Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.
Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.
“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.
In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.
Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.
These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.
The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”
Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.
“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”
A version of this article appeared on Medscape.com.
SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.
Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.
While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.
Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”
Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.
Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.
Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.
“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.
In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.
Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.
These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.
The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”
Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.
“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”
A version of this article appeared on Medscape.com.
AT ACR 2023
Telitacicept shows efficacy, safety in methotrexate-resistant RA
SAN DIEGO – A new randomized, double-blind, phase 3 study of the first-in-class drug telitacicept showed efficacy and safety in patients aged 18-65 with rheumatoid arthritis who were resistant to methotrexate, researchers reported at the annual meeting of the American College of Rheumatology.
Telitacicept is a recombinant fusion protein that aims to target and neutralize B lymphocyte stimulator (also known as B-cell activating factor) and a proliferation-inducing ligand (APRIL), both of which are linked to autoimmunity. Per the industry-funded trial, patients who took 160 mg weekly of the drug versus placebo for 24 weeks met the primary endpoint of achieving at least a 20% improvement in ACR response criteria (60.0% vs. 26.9%, respectively, P < .001), researcher Qing Zuraw, MD, MPH, MBA, of drug developer RemeGen, said in her presentation.
Rheumatologist Jeffrey A. Sparks MD, MMSc, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, who did not take part in the study but is familiar with the findings, said in an interview that the results are promising. “The magnitude of effect is impressive, and it seems it was well tolerated with relatively few serious adverse events. I would want to see this replicated in other patient populations. Also, more data are needed to truly establish safety.”
He added that, “once more data emerges, there would be a debate on where to place this in the treatment lines.”
According to Dr. Sparks, nearly half of patients with RA either cannot tolerate methotrexate or have partial or no response. “There are currently several available treatment options. These patients typically use either [tumor necrosis factor] inhibitors, another targeted medication, or combination therapy.”
Telitacicept is approved in China to treat systemic lupus erythematosus, Dr. Zuraw noted.
The researchers randomly assigned patients with moderate to severe RA at a 3:1 ratio to the drug (n = 360) or placebo (n = 119). The participants were aged 18-65 with a mean age of 49-50 depending on group, and 81.1%-87.4% females depending on group. Ethnicity/race was not reported.
At week 24, patients in the telitacicept group were more likely to achieve an ACR 50 response versus placebo (21.4% vs. 5.9%, respectively; P < .001).
“Significantly more patients in the telitacicept 160 mg group showed no radiographic progression (change in modified Total Sharp Score [mTSS] ≤ 0) at week 24, compared with placebo (90.2% vs. 66.4%; P < .001),” the researchers reported. “Additionally, patients in the telitacicept 160-mg group showed significantly less progression of joint damage (as measured by mTSS, joint space narrowing score, erosion score) from baseline to week 24.”
Treatment-emergent adverse effect levels were similar between the two groups (79.7% in the drug group and 77.3% in the placebo group), as were serious adverse events (6.4% and 6.7%, respectively) and infections/infestations (41.1% and 42.0%, respectively).
Dr. Zuraw noted limitations: The trial lacked a comparator treatment, and the study took place in a Chinese population with limited racial diversity.
In a Q&A session following Dr. Zuraw’s presentation, an audience member offered some perspective instead of a question by noting that most biologic drugs reach an ACR 20 response rate of about 60%, and most fail to move patients to low disease activity. “That’s the case for your product,” he told Dr. Zuraw. “That’s true for basically everything.”
He added that failing to discuss clinical importance is “a flaw of many talks.”
Dr. Zuraw responded that the many drugs do indeed have a response rate in the range of 60%, and she said the company will consider providing information about clinical impact in future talks.
No information is available about the potential cost of the drug. “This targets two proteins, so it is possible that it could have additional costs than typical biologics,” Dr. Sparks said.
RemeGen funded the study. Dr. Zuraw and some other authors disclosed financial relationships with RemeGen. Dr. Sparks reported receiving support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Gordon and Llura Gund Foundation; research support from Bristol-Myers Squibb; and consulting for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova, Janssen, Optum, Pfizer, Recor, Sobi, and UCB.
SAN DIEGO – A new randomized, double-blind, phase 3 study of the first-in-class drug telitacicept showed efficacy and safety in patients aged 18-65 with rheumatoid arthritis who were resistant to methotrexate, researchers reported at the annual meeting of the American College of Rheumatology.
Telitacicept is a recombinant fusion protein that aims to target and neutralize B lymphocyte stimulator (also known as B-cell activating factor) and a proliferation-inducing ligand (APRIL), both of which are linked to autoimmunity. Per the industry-funded trial, patients who took 160 mg weekly of the drug versus placebo for 24 weeks met the primary endpoint of achieving at least a 20% improvement in ACR response criteria (60.0% vs. 26.9%, respectively, P < .001), researcher Qing Zuraw, MD, MPH, MBA, of drug developer RemeGen, said in her presentation.
Rheumatologist Jeffrey A. Sparks MD, MMSc, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, who did not take part in the study but is familiar with the findings, said in an interview that the results are promising. “The magnitude of effect is impressive, and it seems it was well tolerated with relatively few serious adverse events. I would want to see this replicated in other patient populations. Also, more data are needed to truly establish safety.”
He added that, “once more data emerges, there would be a debate on where to place this in the treatment lines.”
According to Dr. Sparks, nearly half of patients with RA either cannot tolerate methotrexate or have partial or no response. “There are currently several available treatment options. These patients typically use either [tumor necrosis factor] inhibitors, another targeted medication, or combination therapy.”
Telitacicept is approved in China to treat systemic lupus erythematosus, Dr. Zuraw noted.
The researchers randomly assigned patients with moderate to severe RA at a 3:1 ratio to the drug (n = 360) or placebo (n = 119). The participants were aged 18-65 with a mean age of 49-50 depending on group, and 81.1%-87.4% females depending on group. Ethnicity/race was not reported.
At week 24, patients in the telitacicept group were more likely to achieve an ACR 50 response versus placebo (21.4% vs. 5.9%, respectively; P < .001).
“Significantly more patients in the telitacicept 160 mg group showed no radiographic progression (change in modified Total Sharp Score [mTSS] ≤ 0) at week 24, compared with placebo (90.2% vs. 66.4%; P < .001),” the researchers reported. “Additionally, patients in the telitacicept 160-mg group showed significantly less progression of joint damage (as measured by mTSS, joint space narrowing score, erosion score) from baseline to week 24.”
Treatment-emergent adverse effect levels were similar between the two groups (79.7% in the drug group and 77.3% in the placebo group), as were serious adverse events (6.4% and 6.7%, respectively) and infections/infestations (41.1% and 42.0%, respectively).
Dr. Zuraw noted limitations: The trial lacked a comparator treatment, and the study took place in a Chinese population with limited racial diversity.
In a Q&A session following Dr. Zuraw’s presentation, an audience member offered some perspective instead of a question by noting that most biologic drugs reach an ACR 20 response rate of about 60%, and most fail to move patients to low disease activity. “That’s the case for your product,” he told Dr. Zuraw. “That’s true for basically everything.”
He added that failing to discuss clinical importance is “a flaw of many talks.”
Dr. Zuraw responded that the many drugs do indeed have a response rate in the range of 60%, and she said the company will consider providing information about clinical impact in future talks.
No information is available about the potential cost of the drug. “This targets two proteins, so it is possible that it could have additional costs than typical biologics,” Dr. Sparks said.
RemeGen funded the study. Dr. Zuraw and some other authors disclosed financial relationships with RemeGen. Dr. Sparks reported receiving support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Gordon and Llura Gund Foundation; research support from Bristol-Myers Squibb; and consulting for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova, Janssen, Optum, Pfizer, Recor, Sobi, and UCB.
SAN DIEGO – A new randomized, double-blind, phase 3 study of the first-in-class drug telitacicept showed efficacy and safety in patients aged 18-65 with rheumatoid arthritis who were resistant to methotrexate, researchers reported at the annual meeting of the American College of Rheumatology.
Telitacicept is a recombinant fusion protein that aims to target and neutralize B lymphocyte stimulator (also known as B-cell activating factor) and a proliferation-inducing ligand (APRIL), both of which are linked to autoimmunity. Per the industry-funded trial, patients who took 160 mg weekly of the drug versus placebo for 24 weeks met the primary endpoint of achieving at least a 20% improvement in ACR response criteria (60.0% vs. 26.9%, respectively, P < .001), researcher Qing Zuraw, MD, MPH, MBA, of drug developer RemeGen, said in her presentation.
Rheumatologist Jeffrey A. Sparks MD, MMSc, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, who did not take part in the study but is familiar with the findings, said in an interview that the results are promising. “The magnitude of effect is impressive, and it seems it was well tolerated with relatively few serious adverse events. I would want to see this replicated in other patient populations. Also, more data are needed to truly establish safety.”
He added that, “once more data emerges, there would be a debate on where to place this in the treatment lines.”
According to Dr. Sparks, nearly half of patients with RA either cannot tolerate methotrexate or have partial or no response. “There are currently several available treatment options. These patients typically use either [tumor necrosis factor] inhibitors, another targeted medication, or combination therapy.”
Telitacicept is approved in China to treat systemic lupus erythematosus, Dr. Zuraw noted.
The researchers randomly assigned patients with moderate to severe RA at a 3:1 ratio to the drug (n = 360) or placebo (n = 119). The participants were aged 18-65 with a mean age of 49-50 depending on group, and 81.1%-87.4% females depending on group. Ethnicity/race was not reported.
At week 24, patients in the telitacicept group were more likely to achieve an ACR 50 response versus placebo (21.4% vs. 5.9%, respectively; P < .001).
“Significantly more patients in the telitacicept 160 mg group showed no radiographic progression (change in modified Total Sharp Score [mTSS] ≤ 0) at week 24, compared with placebo (90.2% vs. 66.4%; P < .001),” the researchers reported. “Additionally, patients in the telitacicept 160-mg group showed significantly less progression of joint damage (as measured by mTSS, joint space narrowing score, erosion score) from baseline to week 24.”
Treatment-emergent adverse effect levels were similar between the two groups (79.7% in the drug group and 77.3% in the placebo group), as were serious adverse events (6.4% and 6.7%, respectively) and infections/infestations (41.1% and 42.0%, respectively).
Dr. Zuraw noted limitations: The trial lacked a comparator treatment, and the study took place in a Chinese population with limited racial diversity.
In a Q&A session following Dr. Zuraw’s presentation, an audience member offered some perspective instead of a question by noting that most biologic drugs reach an ACR 20 response rate of about 60%, and most fail to move patients to low disease activity. “That’s the case for your product,” he told Dr. Zuraw. “That’s true for basically everything.”
He added that failing to discuss clinical importance is “a flaw of many talks.”
Dr. Zuraw responded that the many drugs do indeed have a response rate in the range of 60%, and she said the company will consider providing information about clinical impact in future talks.
No information is available about the potential cost of the drug. “This targets two proteins, so it is possible that it could have additional costs than typical biologics,” Dr. Sparks said.
RemeGen funded the study. Dr. Zuraw and some other authors disclosed financial relationships with RemeGen. Dr. Sparks reported receiving support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Gordon and Llura Gund Foundation; research support from Bristol-Myers Squibb; and consulting for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova, Janssen, Optum, Pfizer, Recor, Sobi, and UCB.
AT ACR 2023
Cold-water swimming for your health? These docs say jump in
Adam Boggon, MBChB, was working at the Royal Free Hospital in North London during the city’s second wave of COVID-19. “I was effectively living in the hospital,” he recalled. “It felt like I was going 10,000 miles per hour, trying to corral hundreds of medical students and doctors.”
During a national lockdown, there were few places Dr. Boggon could escape to, but the Hampstead Heath swimming ponds mostly remained open. He swam there regularly to exercise and recharge even in winter.
“Swimming in cold water takes you out of yourself,” Dr. Boggon said. “It was such a release for someone who grew up in a rural place and had access to green space, even though the water is murky.” It also hovers around 50 °F (10 °C).
Jumping into cold water, well, kind of stinks. So why do it? It’s not only for bragging rights. , specifically to improve depression symptoms and even ease inflammatory conditions.
And a lot of that research is driven by medical pros who love to do it themselves.
For Dr. Boggon, swimming in frigid water is uncomfortable, but he feels that a sensation of calmness follows that makes the plunge more than worth it. Now a Fulbright Scholar at Harvard, where he studies public health and health management, Dr. Boggon is able to frequent the fabled Walden Pond just outside of Boston.
As Thoreau himself said, “You can never have enough of nature.”
Yes, even if it’s really, really cold.
Taking a deeper dive
Heather Massey, PhD, a senior lecturer in Sport, Health, and Exercise Science at University of Portsmouth, blames her father, a dinghy sailor, for her affinity for cold-water swimming.
And she’s done more than most, including an epic 16-hour crossing of the English Channel. The water temperature was in the upper-50s °F, and she swam without a wetsuit. “Time just seemed to collapse,” she has shared about the experience.
While working on her PhD and studying the effects of environmental physiology, in particular what happens to the body when it gets hot or cold, Dr. Massey’s hobby and studies seemed to coalesce.
Her research initially focused on the hazards around being in cold open water. But she also noticed a growing trend of people claiming health benefits from the practice. “People started to talk about experiencing improved symptoms of depression or improved mental health from their activities in the water,” she said.
She partnered with another outdoor swimming enthusiast, Hannah Denton, a counseling psychologist working for the National Health Service in the United Kingdom. Ms. Denton was publishing papers on the potential impact that outdoor swimming may have on people with depression and how it could improve mental health in general. She also regularly engages in cold-water swims to boost feelings of mindfulness and peace.
“Having the experience of being so close to nature, as well as the strong sensory experience of being in cold water, does really encourage you to be in the moment,” Ms. Denton wrote in an article for the Sussex Mindfulness Centre. “My experiences of sea swimming and mindfulness support each other. Both have made me feel more comfortable with my body, to have more of a present moment focus, to pay attention to my breathing, and to gain distance from difficult thoughts.”
Over the past few years, Dr. Massey and Ms. Denton have moved from fairly small-scale studies with no real controls to today, completing a randomized controlled trial and looking at the impact that outdoor swimming may have on people living with mild to moderate depression.
“At first, people sort of thought our idea was a bit wacky,” said Dr. Massey. “Now, the popularity of open-water swimming has really blossomed, and so has this area of research. We’re starting to build more rigor into the work.”
Like all the researchers and physicians interviewed for this article, Dr. Massey hesitates to claim that cold-water swimming is a “cure” that should be medicalized.
“It’s not about prescribing it or forcing people to do it,” said Dr. Massey. “This is not something that a doctor should write on a prescription and say you should go and have eight 1-hour sessions of swimming.”
(Not yet) a common cure
Enter into the conversation Mark Harper, MD, PhD, consultant anesthetist at Sussex University Hospitals in the United Kingdom and Kristiansand, Norway. Dr. Harper is the author of the 2022 book, Chill: The Cold Water Swim Cure – A Transformative Guide to Renew Your Body and Mind.
Dr. Harper grew up swimming in pools, and it wasn’t until his pool closed for 2 weeks that he ventured into the sea. He recalled walking up the beach afterward, thinking, God, this feels good, and from that moment on, he became hooked on outdoor swimming and curious about its therapeutic potential.
The “cure” in the book’s title, Dr. Harper explained, is being used in the historical sense of “treatment,” as in the first medical book about sea-bathing written over 250 years ago. Dr. Harper acknowledged that the connection to health is still speculative. “However, the circumstantial evidence, the feedback from participants and early study data for its benefits are now very strong,” he said.
In a small study published in 2022, Dr. Harper and colleagues took 59 people with anxiety and depression and put them through a sea-swimming course. Afterward, 80% showed a clinically significant improvement in their mental health.
More recently, Dr. Harper and his team of researchers released a survey to determine how many people were using cold-water swimming as a treatment for a mental or physical ailment. “We thought 30 or 40 people would respond, but we ended up with over 700,” he said. “The majority were using it for mental health but also included inflammation-related conditions.”
Over 2 decades, Dr. Harper has seen dramatic success stories. In his book, he recalled a good friend who, in his early 20s, suffered from Crohn’s disease so badly he couldn’t walk up the steps to his parents’ house. The friend turned to outdoor cold swimming as a low-impact workout and began noticing the symptoms of his disease were improving. Within months, he was able to go off his medications. In 2022, he completed 52 triathlons: one per week for the entire year.
How cold exposure may play with your brain
Vaibhav Diwadkar, PhD, professor of psychiatry and behavioral neurosciences at Wayne State University, in Detroit, is studying how human brain networks respond to cold exposure. Dr. Diwadkar and his colleague, Otto Muzik, PhD, began by putting volunteers in a rubber suit with thin tubing and infusing the tubing with temperature-controlled water. Meanwhile, they collected functional brain imaging data to analyze which parts of the brain were responding as body temperature changed.
The data showed that the cold exposure made certain areas of the brain very active, including some that have been associated with the regulation of mood.
Dr. Diwadkar posits that controlled exposure to cold serves as a low-level stressor that knocks different systems within the brain and body out of homeostasis. Once the stress is removed, the brain responds by releasing neurotransmitters that enhance mood, frequently leading to feelings of euphoria in participants.
“We don’t have direct evidence of such a mechanism, but it’s a reasonable speculation,” said Dr. Diwadkar.
However, he pointed out that science writers in the media often portray topics such as this one in black and white, which is “oversimplifying the scientific complexity of biology.”
Clearly, more research needs to be done on the potential therapeutic benefits of cold-water swimming. But for those suffering from anxiety, depression, or chronic illness, if taking a cold dip makes you feel better, the why and how might be beside the point.
Plus, as Dr. Harper pointed out, it’s an easy and accessible therapy.
“All you need is some water – enough to submerge your entire body in – that’s less than 68 °F (20 °C),” he said. “If you stay long enough to get over that initial shock, which is just 2 or 3 minutes, then you’ve got the effect. If you get out and want to go back in again, then you’ve done it right.”
A version of this article first appeared on Medscape.com.
Adam Boggon, MBChB, was working at the Royal Free Hospital in North London during the city’s second wave of COVID-19. “I was effectively living in the hospital,” he recalled. “It felt like I was going 10,000 miles per hour, trying to corral hundreds of medical students and doctors.”
During a national lockdown, there were few places Dr. Boggon could escape to, but the Hampstead Heath swimming ponds mostly remained open. He swam there regularly to exercise and recharge even in winter.
“Swimming in cold water takes you out of yourself,” Dr. Boggon said. “It was such a release for someone who grew up in a rural place and had access to green space, even though the water is murky.” It also hovers around 50 °F (10 °C).
Jumping into cold water, well, kind of stinks. So why do it? It’s not only for bragging rights. , specifically to improve depression symptoms and even ease inflammatory conditions.
And a lot of that research is driven by medical pros who love to do it themselves.
For Dr. Boggon, swimming in frigid water is uncomfortable, but he feels that a sensation of calmness follows that makes the plunge more than worth it. Now a Fulbright Scholar at Harvard, where he studies public health and health management, Dr. Boggon is able to frequent the fabled Walden Pond just outside of Boston.
As Thoreau himself said, “You can never have enough of nature.”
Yes, even if it’s really, really cold.
Taking a deeper dive
Heather Massey, PhD, a senior lecturer in Sport, Health, and Exercise Science at University of Portsmouth, blames her father, a dinghy sailor, for her affinity for cold-water swimming.
And she’s done more than most, including an epic 16-hour crossing of the English Channel. The water temperature was in the upper-50s °F, and she swam without a wetsuit. “Time just seemed to collapse,” she has shared about the experience.
While working on her PhD and studying the effects of environmental physiology, in particular what happens to the body when it gets hot or cold, Dr. Massey’s hobby and studies seemed to coalesce.
Her research initially focused on the hazards around being in cold open water. But she also noticed a growing trend of people claiming health benefits from the practice. “People started to talk about experiencing improved symptoms of depression or improved mental health from their activities in the water,” she said.
She partnered with another outdoor swimming enthusiast, Hannah Denton, a counseling psychologist working for the National Health Service in the United Kingdom. Ms. Denton was publishing papers on the potential impact that outdoor swimming may have on people with depression and how it could improve mental health in general. She also regularly engages in cold-water swims to boost feelings of mindfulness and peace.
“Having the experience of being so close to nature, as well as the strong sensory experience of being in cold water, does really encourage you to be in the moment,” Ms. Denton wrote in an article for the Sussex Mindfulness Centre. “My experiences of sea swimming and mindfulness support each other. Both have made me feel more comfortable with my body, to have more of a present moment focus, to pay attention to my breathing, and to gain distance from difficult thoughts.”
Over the past few years, Dr. Massey and Ms. Denton have moved from fairly small-scale studies with no real controls to today, completing a randomized controlled trial and looking at the impact that outdoor swimming may have on people living with mild to moderate depression.
“At first, people sort of thought our idea was a bit wacky,” said Dr. Massey. “Now, the popularity of open-water swimming has really blossomed, and so has this area of research. We’re starting to build more rigor into the work.”
Like all the researchers and physicians interviewed for this article, Dr. Massey hesitates to claim that cold-water swimming is a “cure” that should be medicalized.
“It’s not about prescribing it or forcing people to do it,” said Dr. Massey. “This is not something that a doctor should write on a prescription and say you should go and have eight 1-hour sessions of swimming.”
(Not yet) a common cure
Enter into the conversation Mark Harper, MD, PhD, consultant anesthetist at Sussex University Hospitals in the United Kingdom and Kristiansand, Norway. Dr. Harper is the author of the 2022 book, Chill: The Cold Water Swim Cure – A Transformative Guide to Renew Your Body and Mind.
Dr. Harper grew up swimming in pools, and it wasn’t until his pool closed for 2 weeks that he ventured into the sea. He recalled walking up the beach afterward, thinking, God, this feels good, and from that moment on, he became hooked on outdoor swimming and curious about its therapeutic potential.
The “cure” in the book’s title, Dr. Harper explained, is being used in the historical sense of “treatment,” as in the first medical book about sea-bathing written over 250 years ago. Dr. Harper acknowledged that the connection to health is still speculative. “However, the circumstantial evidence, the feedback from participants and early study data for its benefits are now very strong,” he said.
In a small study published in 2022, Dr. Harper and colleagues took 59 people with anxiety and depression and put them through a sea-swimming course. Afterward, 80% showed a clinically significant improvement in their mental health.
More recently, Dr. Harper and his team of researchers released a survey to determine how many people were using cold-water swimming as a treatment for a mental or physical ailment. “We thought 30 or 40 people would respond, but we ended up with over 700,” he said. “The majority were using it for mental health but also included inflammation-related conditions.”
Over 2 decades, Dr. Harper has seen dramatic success stories. In his book, he recalled a good friend who, in his early 20s, suffered from Crohn’s disease so badly he couldn’t walk up the steps to his parents’ house. The friend turned to outdoor cold swimming as a low-impact workout and began noticing the symptoms of his disease were improving. Within months, he was able to go off his medications. In 2022, he completed 52 triathlons: one per week for the entire year.
How cold exposure may play with your brain
Vaibhav Diwadkar, PhD, professor of psychiatry and behavioral neurosciences at Wayne State University, in Detroit, is studying how human brain networks respond to cold exposure. Dr. Diwadkar and his colleague, Otto Muzik, PhD, began by putting volunteers in a rubber suit with thin tubing and infusing the tubing with temperature-controlled water. Meanwhile, they collected functional brain imaging data to analyze which parts of the brain were responding as body temperature changed.
The data showed that the cold exposure made certain areas of the brain very active, including some that have been associated with the regulation of mood.
Dr. Diwadkar posits that controlled exposure to cold serves as a low-level stressor that knocks different systems within the brain and body out of homeostasis. Once the stress is removed, the brain responds by releasing neurotransmitters that enhance mood, frequently leading to feelings of euphoria in participants.
“We don’t have direct evidence of such a mechanism, but it’s a reasonable speculation,” said Dr. Diwadkar.
However, he pointed out that science writers in the media often portray topics such as this one in black and white, which is “oversimplifying the scientific complexity of biology.”
Clearly, more research needs to be done on the potential therapeutic benefits of cold-water swimming. But for those suffering from anxiety, depression, or chronic illness, if taking a cold dip makes you feel better, the why and how might be beside the point.
Plus, as Dr. Harper pointed out, it’s an easy and accessible therapy.
“All you need is some water – enough to submerge your entire body in – that’s less than 68 °F (20 °C),” he said. “If you stay long enough to get over that initial shock, which is just 2 or 3 minutes, then you’ve got the effect. If you get out and want to go back in again, then you’ve done it right.”
A version of this article first appeared on Medscape.com.
Adam Boggon, MBChB, was working at the Royal Free Hospital in North London during the city’s second wave of COVID-19. “I was effectively living in the hospital,” he recalled. “It felt like I was going 10,000 miles per hour, trying to corral hundreds of medical students and doctors.”
During a national lockdown, there were few places Dr. Boggon could escape to, but the Hampstead Heath swimming ponds mostly remained open. He swam there regularly to exercise and recharge even in winter.
“Swimming in cold water takes you out of yourself,” Dr. Boggon said. “It was such a release for someone who grew up in a rural place and had access to green space, even though the water is murky.” It also hovers around 50 °F (10 °C).
Jumping into cold water, well, kind of stinks. So why do it? It’s not only for bragging rights. , specifically to improve depression symptoms and even ease inflammatory conditions.
And a lot of that research is driven by medical pros who love to do it themselves.
For Dr. Boggon, swimming in frigid water is uncomfortable, but he feels that a sensation of calmness follows that makes the plunge more than worth it. Now a Fulbright Scholar at Harvard, where he studies public health and health management, Dr. Boggon is able to frequent the fabled Walden Pond just outside of Boston.
As Thoreau himself said, “You can never have enough of nature.”
Yes, even if it’s really, really cold.
Taking a deeper dive
Heather Massey, PhD, a senior lecturer in Sport, Health, and Exercise Science at University of Portsmouth, blames her father, a dinghy sailor, for her affinity for cold-water swimming.
And she’s done more than most, including an epic 16-hour crossing of the English Channel. The water temperature was in the upper-50s °F, and she swam without a wetsuit. “Time just seemed to collapse,” she has shared about the experience.
While working on her PhD and studying the effects of environmental physiology, in particular what happens to the body when it gets hot or cold, Dr. Massey’s hobby and studies seemed to coalesce.
Her research initially focused on the hazards around being in cold open water. But she also noticed a growing trend of people claiming health benefits from the practice. “People started to talk about experiencing improved symptoms of depression or improved mental health from their activities in the water,” she said.
She partnered with another outdoor swimming enthusiast, Hannah Denton, a counseling psychologist working for the National Health Service in the United Kingdom. Ms. Denton was publishing papers on the potential impact that outdoor swimming may have on people with depression and how it could improve mental health in general. She also regularly engages in cold-water swims to boost feelings of mindfulness and peace.
“Having the experience of being so close to nature, as well as the strong sensory experience of being in cold water, does really encourage you to be in the moment,” Ms. Denton wrote in an article for the Sussex Mindfulness Centre. “My experiences of sea swimming and mindfulness support each other. Both have made me feel more comfortable with my body, to have more of a present moment focus, to pay attention to my breathing, and to gain distance from difficult thoughts.”
Over the past few years, Dr. Massey and Ms. Denton have moved from fairly small-scale studies with no real controls to today, completing a randomized controlled trial and looking at the impact that outdoor swimming may have on people living with mild to moderate depression.
“At first, people sort of thought our idea was a bit wacky,” said Dr. Massey. “Now, the popularity of open-water swimming has really blossomed, and so has this area of research. We’re starting to build more rigor into the work.”
Like all the researchers and physicians interviewed for this article, Dr. Massey hesitates to claim that cold-water swimming is a “cure” that should be medicalized.
“It’s not about prescribing it or forcing people to do it,” said Dr. Massey. “This is not something that a doctor should write on a prescription and say you should go and have eight 1-hour sessions of swimming.”
(Not yet) a common cure
Enter into the conversation Mark Harper, MD, PhD, consultant anesthetist at Sussex University Hospitals in the United Kingdom and Kristiansand, Norway. Dr. Harper is the author of the 2022 book, Chill: The Cold Water Swim Cure – A Transformative Guide to Renew Your Body and Mind.
Dr. Harper grew up swimming in pools, and it wasn’t until his pool closed for 2 weeks that he ventured into the sea. He recalled walking up the beach afterward, thinking, God, this feels good, and from that moment on, he became hooked on outdoor swimming and curious about its therapeutic potential.
The “cure” in the book’s title, Dr. Harper explained, is being used in the historical sense of “treatment,” as in the first medical book about sea-bathing written over 250 years ago. Dr. Harper acknowledged that the connection to health is still speculative. “However, the circumstantial evidence, the feedback from participants and early study data for its benefits are now very strong,” he said.
In a small study published in 2022, Dr. Harper and colleagues took 59 people with anxiety and depression and put them through a sea-swimming course. Afterward, 80% showed a clinically significant improvement in their mental health.
More recently, Dr. Harper and his team of researchers released a survey to determine how many people were using cold-water swimming as a treatment for a mental or physical ailment. “We thought 30 or 40 people would respond, but we ended up with over 700,” he said. “The majority were using it for mental health but also included inflammation-related conditions.”
Over 2 decades, Dr. Harper has seen dramatic success stories. In his book, he recalled a good friend who, in his early 20s, suffered from Crohn’s disease so badly he couldn’t walk up the steps to his parents’ house. The friend turned to outdoor cold swimming as a low-impact workout and began noticing the symptoms of his disease were improving. Within months, he was able to go off his medications. In 2022, he completed 52 triathlons: one per week for the entire year.
How cold exposure may play with your brain
Vaibhav Diwadkar, PhD, professor of psychiatry and behavioral neurosciences at Wayne State University, in Detroit, is studying how human brain networks respond to cold exposure. Dr. Diwadkar and his colleague, Otto Muzik, PhD, began by putting volunteers in a rubber suit with thin tubing and infusing the tubing with temperature-controlled water. Meanwhile, they collected functional brain imaging data to analyze which parts of the brain were responding as body temperature changed.
The data showed that the cold exposure made certain areas of the brain very active, including some that have been associated with the regulation of mood.
Dr. Diwadkar posits that controlled exposure to cold serves as a low-level stressor that knocks different systems within the brain and body out of homeostasis. Once the stress is removed, the brain responds by releasing neurotransmitters that enhance mood, frequently leading to feelings of euphoria in participants.
“We don’t have direct evidence of such a mechanism, but it’s a reasonable speculation,” said Dr. Diwadkar.
However, he pointed out that science writers in the media often portray topics such as this one in black and white, which is “oversimplifying the scientific complexity of biology.”
Clearly, more research needs to be done on the potential therapeutic benefits of cold-water swimming. But for those suffering from anxiety, depression, or chronic illness, if taking a cold dip makes you feel better, the why and how might be beside the point.
Plus, as Dr. Harper pointed out, it’s an easy and accessible therapy.
“All you need is some water – enough to submerge your entire body in – that’s less than 68 °F (20 °C),” he said. “If you stay long enough to get over that initial shock, which is just 2 or 3 minutes, then you’ve got the effect. If you get out and want to go back in again, then you’ve done it right.”
A version of this article first appeared on Medscape.com.
Novel blood test can detect RA
SAN DIEGO – Researchers say they’ve developed a novel blood-based assay that can differentiate patients with seropositive or seronegative rheumatoid arthritis from healthy people and those with other inflammatory diseases or osteoarthritis.
While cautioning that the results need to be confirmed, University of Oxford (England) rheumatologist Peter Taylor, PhD, MA, told an audience at the annual meeting of the American College of Rheumatology that the test has an overall mean sensitivity of 90.8% (standard deviation, 0.94%; 95% confidence interval, 83.2%-95.4%) and mean specificity of 96.1% (SD, 0.64%; 95% CI, 92.7%-97.9%). The mean area under the curve (AUC) is 0.991 (SD, 0.001; 95% CI, 97.2%-99.6%).
“That is to say that it can correctly identify 96% of people without rheumatoid arthritis, and it can correctly identify over 90% of those who do have rheumatoid arthritis,” Dr. Taylor said. In the big picture, he said, “we’ve developed a blood-based assay that detects both organ-specific and systemic biological processes in patients with rheumatoid arthritis.”
Rheumatologist Kevin W. Byram, MD, of Vanderbilt University, Nashville, Tenn., who did not take part in the study but is familiar with its findings, noted in an interview that “there is a constant search for biomarkers to help aide in more accurate and faster diagnosis of all rheumatic conditions, including RA.”
He added that “a common clinical scenario for the rheumatologist is a patient presenting with painful and/or swollen joints and other features that might suggest a few different diagnoses. A diagnostic assay like this might help distinguish patients with RA from other inflammatory conditions or non-inflammatory conditions that might mimic RA.”
In his presentation, Dr. Taylor noted that “we haven’t yet integrated precision medicine into routine clinical practice in rheumatology.” While blood-based assays are prevalent in other types of clinical diagnostics, rheumatology relies on synovial biopsies that are “rarely used in routine clinical practice,” he said.
The new test is a “non-invasive DNA capture assay that can identify specific gene expression from synovium-specific signatures in blood plasma of patients with rheumatoid arthritis,” Dr. Taylor said. Specifically, it focuses on the “unique patterns and sizes of cell-free DNA,” he said. “Analysis of [long] fragments has the potential to give us a great deal of information about disease progression, potentially about customizing treatments and even evaluating the effectiveness of therapies.”
For the new study, researchers examined 229 samples from 191 patients, of whom 63.3% were White and 67.9% were female, with a median age of 56. A total of 89 patients with RA provided 89 samples and 102 without RA provided 140 samples, including 29 healthy controls (66 samples) and others with conditions such as psoriatic arthritis, ulcerative colitis, and osteoarthritis.
The machine learning model “identified 3,425 epigenetic features with statistically significant discrimination between the patients with and without rheumatoid arthritis,” Dr. Taylor said. These features were mapped to 929 genes which had some overlap with known blood pathway genes.
“Over and above that, there’s a whole set of these epigenetic features which represent novel pathways and potentially rich hunting ground for therapeutic targets and other translational investigation,” he said.
For seronegative cases, mean AUC was 0.971 (SD, 0.001; 95% CI, 93.8%-99.2%), sensitivity was 83.7% (SD, 2.03; 95% CI, 63.3%-91.8%) and specificity was 95.4% (SD, 0.69; 95% CI, 90.8%-97.5%).
Specificity for RA versus healthy controls was 100 (SD, 0; 95% CI, 94.4-100.0).
Dr. Byram described the study as small but intriguing. He cautioned that “there is always some likelihood that the actual components of the test are just recognizing some combination of things we are already testing in the clinic,” he said. Details about the patients in the study can offer insight into “whether the assay is actually just recognizing something about patients with RA that is truly different, or rather is it recognizing how a common factor among patients with RA is transcribed by the cell.”
Moving forward, “it is important to get a grasp of how these biomarkers might perform in various settings,” he said.
Dr. Taylor did not discuss the potential cost of the assay in his presentation. “Tests like these have to strike a real balance in being useful and cost-effective and, since they are still made by commercial companies with commercial interests, also make a margin for their owner,” Dr. Byram said. “Turnaround time is also an important factor to think about.”
Aqtual funded the study. Dr. Taylor reports consulting for AbbVie, Aqtual, Biogen, Fresenius Kabi, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Nordic Pharma, Pfizer, Sanofi, and UCB and receiving grant support from Galapagos. The other study authors all have relationships with Aqtual, and some report various other disclosures. Dr. Byram has no disclosures.
SAN DIEGO – Researchers say they’ve developed a novel blood-based assay that can differentiate patients with seropositive or seronegative rheumatoid arthritis from healthy people and those with other inflammatory diseases or osteoarthritis.
While cautioning that the results need to be confirmed, University of Oxford (England) rheumatologist Peter Taylor, PhD, MA, told an audience at the annual meeting of the American College of Rheumatology that the test has an overall mean sensitivity of 90.8% (standard deviation, 0.94%; 95% confidence interval, 83.2%-95.4%) and mean specificity of 96.1% (SD, 0.64%; 95% CI, 92.7%-97.9%). The mean area under the curve (AUC) is 0.991 (SD, 0.001; 95% CI, 97.2%-99.6%).
“That is to say that it can correctly identify 96% of people without rheumatoid arthritis, and it can correctly identify over 90% of those who do have rheumatoid arthritis,” Dr. Taylor said. In the big picture, he said, “we’ve developed a blood-based assay that detects both organ-specific and systemic biological processes in patients with rheumatoid arthritis.”
Rheumatologist Kevin W. Byram, MD, of Vanderbilt University, Nashville, Tenn., who did not take part in the study but is familiar with its findings, noted in an interview that “there is a constant search for biomarkers to help aide in more accurate and faster diagnosis of all rheumatic conditions, including RA.”
He added that “a common clinical scenario for the rheumatologist is a patient presenting with painful and/or swollen joints and other features that might suggest a few different diagnoses. A diagnostic assay like this might help distinguish patients with RA from other inflammatory conditions or non-inflammatory conditions that might mimic RA.”
In his presentation, Dr. Taylor noted that “we haven’t yet integrated precision medicine into routine clinical practice in rheumatology.” While blood-based assays are prevalent in other types of clinical diagnostics, rheumatology relies on synovial biopsies that are “rarely used in routine clinical practice,” he said.
The new test is a “non-invasive DNA capture assay that can identify specific gene expression from synovium-specific signatures in blood plasma of patients with rheumatoid arthritis,” Dr. Taylor said. Specifically, it focuses on the “unique patterns and sizes of cell-free DNA,” he said. “Analysis of [long] fragments has the potential to give us a great deal of information about disease progression, potentially about customizing treatments and even evaluating the effectiveness of therapies.”
For the new study, researchers examined 229 samples from 191 patients, of whom 63.3% were White and 67.9% were female, with a median age of 56. A total of 89 patients with RA provided 89 samples and 102 without RA provided 140 samples, including 29 healthy controls (66 samples) and others with conditions such as psoriatic arthritis, ulcerative colitis, and osteoarthritis.
The machine learning model “identified 3,425 epigenetic features with statistically significant discrimination between the patients with and without rheumatoid arthritis,” Dr. Taylor said. These features were mapped to 929 genes which had some overlap with known blood pathway genes.
“Over and above that, there’s a whole set of these epigenetic features which represent novel pathways and potentially rich hunting ground for therapeutic targets and other translational investigation,” he said.
For seronegative cases, mean AUC was 0.971 (SD, 0.001; 95% CI, 93.8%-99.2%), sensitivity was 83.7% (SD, 2.03; 95% CI, 63.3%-91.8%) and specificity was 95.4% (SD, 0.69; 95% CI, 90.8%-97.5%).
Specificity for RA versus healthy controls was 100 (SD, 0; 95% CI, 94.4-100.0).
Dr. Byram described the study as small but intriguing. He cautioned that “there is always some likelihood that the actual components of the test are just recognizing some combination of things we are already testing in the clinic,” he said. Details about the patients in the study can offer insight into “whether the assay is actually just recognizing something about patients with RA that is truly different, or rather is it recognizing how a common factor among patients with RA is transcribed by the cell.”
Moving forward, “it is important to get a grasp of how these biomarkers might perform in various settings,” he said.
Dr. Taylor did not discuss the potential cost of the assay in his presentation. “Tests like these have to strike a real balance in being useful and cost-effective and, since they are still made by commercial companies with commercial interests, also make a margin for their owner,” Dr. Byram said. “Turnaround time is also an important factor to think about.”
Aqtual funded the study. Dr. Taylor reports consulting for AbbVie, Aqtual, Biogen, Fresenius Kabi, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Nordic Pharma, Pfizer, Sanofi, and UCB and receiving grant support from Galapagos. The other study authors all have relationships with Aqtual, and some report various other disclosures. Dr. Byram has no disclosures.
SAN DIEGO – Researchers say they’ve developed a novel blood-based assay that can differentiate patients with seropositive or seronegative rheumatoid arthritis from healthy people and those with other inflammatory diseases or osteoarthritis.
While cautioning that the results need to be confirmed, University of Oxford (England) rheumatologist Peter Taylor, PhD, MA, told an audience at the annual meeting of the American College of Rheumatology that the test has an overall mean sensitivity of 90.8% (standard deviation, 0.94%; 95% confidence interval, 83.2%-95.4%) and mean specificity of 96.1% (SD, 0.64%; 95% CI, 92.7%-97.9%). The mean area under the curve (AUC) is 0.991 (SD, 0.001; 95% CI, 97.2%-99.6%).
“That is to say that it can correctly identify 96% of people without rheumatoid arthritis, and it can correctly identify over 90% of those who do have rheumatoid arthritis,” Dr. Taylor said. In the big picture, he said, “we’ve developed a blood-based assay that detects both organ-specific and systemic biological processes in patients with rheumatoid arthritis.”
Rheumatologist Kevin W. Byram, MD, of Vanderbilt University, Nashville, Tenn., who did not take part in the study but is familiar with its findings, noted in an interview that “there is a constant search for biomarkers to help aide in more accurate and faster diagnosis of all rheumatic conditions, including RA.”
He added that “a common clinical scenario for the rheumatologist is a patient presenting with painful and/or swollen joints and other features that might suggest a few different diagnoses. A diagnostic assay like this might help distinguish patients with RA from other inflammatory conditions or non-inflammatory conditions that might mimic RA.”
In his presentation, Dr. Taylor noted that “we haven’t yet integrated precision medicine into routine clinical practice in rheumatology.” While blood-based assays are prevalent in other types of clinical diagnostics, rheumatology relies on synovial biopsies that are “rarely used in routine clinical practice,” he said.
The new test is a “non-invasive DNA capture assay that can identify specific gene expression from synovium-specific signatures in blood plasma of patients with rheumatoid arthritis,” Dr. Taylor said. Specifically, it focuses on the “unique patterns and sizes of cell-free DNA,” he said. “Analysis of [long] fragments has the potential to give us a great deal of information about disease progression, potentially about customizing treatments and even evaluating the effectiveness of therapies.”
For the new study, researchers examined 229 samples from 191 patients, of whom 63.3% were White and 67.9% were female, with a median age of 56. A total of 89 patients with RA provided 89 samples and 102 without RA provided 140 samples, including 29 healthy controls (66 samples) and others with conditions such as psoriatic arthritis, ulcerative colitis, and osteoarthritis.
The machine learning model “identified 3,425 epigenetic features with statistically significant discrimination between the patients with and without rheumatoid arthritis,” Dr. Taylor said. These features were mapped to 929 genes which had some overlap with known blood pathway genes.
“Over and above that, there’s a whole set of these epigenetic features which represent novel pathways and potentially rich hunting ground for therapeutic targets and other translational investigation,” he said.
For seronegative cases, mean AUC was 0.971 (SD, 0.001; 95% CI, 93.8%-99.2%), sensitivity was 83.7% (SD, 2.03; 95% CI, 63.3%-91.8%) and specificity was 95.4% (SD, 0.69; 95% CI, 90.8%-97.5%).
Specificity for RA versus healthy controls was 100 (SD, 0; 95% CI, 94.4-100.0).
Dr. Byram described the study as small but intriguing. He cautioned that “there is always some likelihood that the actual components of the test are just recognizing some combination of things we are already testing in the clinic,” he said. Details about the patients in the study can offer insight into “whether the assay is actually just recognizing something about patients with RA that is truly different, or rather is it recognizing how a common factor among patients with RA is transcribed by the cell.”
Moving forward, “it is important to get a grasp of how these biomarkers might perform in various settings,” he said.
Dr. Taylor did not discuss the potential cost of the assay in his presentation. “Tests like these have to strike a real balance in being useful and cost-effective and, since they are still made by commercial companies with commercial interests, also make a margin for their owner,” Dr. Byram said. “Turnaround time is also an important factor to think about.”
Aqtual funded the study. Dr. Taylor reports consulting for AbbVie, Aqtual, Biogen, Fresenius Kabi, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Nordic Pharma, Pfizer, Sanofi, and UCB and receiving grant support from Galapagos. The other study authors all have relationships with Aqtual, and some report various other disclosures. Dr. Byram has no disclosures.
AT ACR 2023
Split-dose methotrexate speeds RA response over single dose
SAN DIEGO – A split dose of methotrexate (MTX) given orally once per week showed significantly higher efficacy in patients with rheumatoid arthritis at 16 weeks, compared with a single MTX dose weekly, according to new research. By 24 weeks, efficacy measures were similar for both groups.
However, fewer patients in the split-dose group needed additional disease-modifying antirheumatic drugs (DMARDs) to control disease activity.
MTX is a highly utilized, inexpensive drug for RA, but only about 30% of patients can achieve low disease activity or remission on MTX monotherapy, said Varun Dhir, MD, MBBS, of the Postgraduate Institute of Medical Education and Research, Chandigarh, India. He co-authored and presented the research at the annual meeting of the American College of Rheumatology.
Part of the problem is that “oral methotrexate absorption from the gut reduces as the doses go up,” Dr. Dhir noted, because the transport mechanism gets saturated. MTX delivered subcutaneously is one way to improve efficacy, but patients can be needle-averse, and in some countries, like India, pre-filled syringes are not available, he said.
There is pharmacokinetic data dating back 20 years that suggest split-dose MTX could be more efficacious. “However, there are no randomized controlled trials to date, and the guidelines therefore are silent on this approach,” Dr. Dhir said.
To address this question, Dr. Dhir and colleagues recruited patients with RA from six centers across India. Patients were aged 18-60 years, seropositive (rheumatoid factor or anti-citrullinated protein antibodies), and had a disease duration of 5 years or fewer. Patients had active disease, defined as at least four tender joints and at least two swollen joints, and were not taking any DMARDs except for hydroxychloroquine and/or low-dose prednisolone.
A total of 253 patients were randomly assigned to a single 25-mg dose or a split-dose of MTX once weekly (10 mg in the morning and 15 mg in the evening on the same day). The primary outcome was a European Alliance of Associations for Rheumatology (EULAR) good response at 24 weeks. At the 16-week mark, if patients had not achieved low disease activity based on a 28-joint Disease Activity Score (DAS28) greater than 3.2, a blinded assessor could add either leflunomide or sulfasalazine to the continued MTX therapy.
At baseline, there was no difference between the groups’ DAS28, but after 16 weeks, DAS28 was significantly lower in the split-dose group, compared with the single-dose group (4.4 vs. 5.1; P < .001), and a higher percentage of patients in the split-dose group had a EULAR good response.
About three-quarters (76.6%) of patients in the split-dose group experienced an improvement of at least 20% in ACR response criteria (ACR20), compared with 52% in the single-dose group. The split-dose group also had higher proportion of patients achieving ACR50 and ACR70.
About one-third of the split-dose group (35%) added an additional DMARD at 16 weeks, compared with 54.5% of the single-dose group (P = .005).
After 24 weeks, DAS28 scores remained lower in the split-dose group (4.1 vs. 4.5; P = .03), but there were no other differences in treatment responses. Health Assessment Questionnaire scores were the same between both groups at 16 and 24 weeks.
The primary outcome was not met, although Dr. Dhir noted a flaw in the study design that could have affected the results. By allowing patients to add additional DMARDs at 16 weeks, “there were two factors which were affecting the primary outcome” at 24 weeks, he told this news organization. “I feel there was a robust result at least at 16 weeks.”
While there were no major adverse events, the split-dose group had higher rates of transaminitis (elevated liver enzymes) during the study, and low white blood cell count was higher in the single-dose group at 24 weeks. There was no difference in MTX intolerance between the two groups.
“It looks like [the split-dose group] gets out of the block faster. It’s a faster effect,” although the other group did catch up, Janet Pope, MD, MPH, of Western University, London, Ont., said in an interview. She was not involved with the research. Two positive results were the earlier ACR responses in the split-dose group as well as fewer patients in that same group needing to add another DMARD to therapy.
“In my opinion, if it’s equal cost, why not try it and see?” she said.
In a separate presentation referring to the abstract, Joan Bathon, MD, director of rheumatology at Columbia University, New York City, noted that these results align with ACR 2021 recommendations. Dr. Bathon was not involved with this study but was on the writing committee establishing those 2021 guidelines.
“The recommendation – with low certainty of evidence – was that for patients who are intolerant to MTX, that split-dose of oral MTX is worth trying before you switch to a different DMARD,” she said. “I think these data support that concept.”
Dr. Dhir and Dr. Bathon had no relevant financial relationships. Dr. Pope disclosed financial relationships with AbbVie/Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Fresenius Kabi, GlaxoSmithKline, Janssen, Mallinckrodt, Novartis, Organon, Pfizer, Sandoz, and Viatris.
A version of this article first appeared on Medscape.com.
SAN DIEGO – A split dose of methotrexate (MTX) given orally once per week showed significantly higher efficacy in patients with rheumatoid arthritis at 16 weeks, compared with a single MTX dose weekly, according to new research. By 24 weeks, efficacy measures were similar for both groups.
However, fewer patients in the split-dose group needed additional disease-modifying antirheumatic drugs (DMARDs) to control disease activity.
MTX is a highly utilized, inexpensive drug for RA, but only about 30% of patients can achieve low disease activity or remission on MTX monotherapy, said Varun Dhir, MD, MBBS, of the Postgraduate Institute of Medical Education and Research, Chandigarh, India. He co-authored and presented the research at the annual meeting of the American College of Rheumatology.
Part of the problem is that “oral methotrexate absorption from the gut reduces as the doses go up,” Dr. Dhir noted, because the transport mechanism gets saturated. MTX delivered subcutaneously is one way to improve efficacy, but patients can be needle-averse, and in some countries, like India, pre-filled syringes are not available, he said.
There is pharmacokinetic data dating back 20 years that suggest split-dose MTX could be more efficacious. “However, there are no randomized controlled trials to date, and the guidelines therefore are silent on this approach,” Dr. Dhir said.
To address this question, Dr. Dhir and colleagues recruited patients with RA from six centers across India. Patients were aged 18-60 years, seropositive (rheumatoid factor or anti-citrullinated protein antibodies), and had a disease duration of 5 years or fewer. Patients had active disease, defined as at least four tender joints and at least two swollen joints, and were not taking any DMARDs except for hydroxychloroquine and/or low-dose prednisolone.
A total of 253 patients were randomly assigned to a single 25-mg dose or a split-dose of MTX once weekly (10 mg in the morning and 15 mg in the evening on the same day). The primary outcome was a European Alliance of Associations for Rheumatology (EULAR) good response at 24 weeks. At the 16-week mark, if patients had not achieved low disease activity based on a 28-joint Disease Activity Score (DAS28) greater than 3.2, a blinded assessor could add either leflunomide or sulfasalazine to the continued MTX therapy.
At baseline, there was no difference between the groups’ DAS28, but after 16 weeks, DAS28 was significantly lower in the split-dose group, compared with the single-dose group (4.4 vs. 5.1; P < .001), and a higher percentage of patients in the split-dose group had a EULAR good response.
About three-quarters (76.6%) of patients in the split-dose group experienced an improvement of at least 20% in ACR response criteria (ACR20), compared with 52% in the single-dose group. The split-dose group also had higher proportion of patients achieving ACR50 and ACR70.
About one-third of the split-dose group (35%) added an additional DMARD at 16 weeks, compared with 54.5% of the single-dose group (P = .005).
After 24 weeks, DAS28 scores remained lower in the split-dose group (4.1 vs. 4.5; P = .03), but there were no other differences in treatment responses. Health Assessment Questionnaire scores were the same between both groups at 16 and 24 weeks.
The primary outcome was not met, although Dr. Dhir noted a flaw in the study design that could have affected the results. By allowing patients to add additional DMARDs at 16 weeks, “there were two factors which were affecting the primary outcome” at 24 weeks, he told this news organization. “I feel there was a robust result at least at 16 weeks.”
While there were no major adverse events, the split-dose group had higher rates of transaminitis (elevated liver enzymes) during the study, and low white blood cell count was higher in the single-dose group at 24 weeks. There was no difference in MTX intolerance between the two groups.
“It looks like [the split-dose group] gets out of the block faster. It’s a faster effect,” although the other group did catch up, Janet Pope, MD, MPH, of Western University, London, Ont., said in an interview. She was not involved with the research. Two positive results were the earlier ACR responses in the split-dose group as well as fewer patients in that same group needing to add another DMARD to therapy.
“In my opinion, if it’s equal cost, why not try it and see?” she said.
In a separate presentation referring to the abstract, Joan Bathon, MD, director of rheumatology at Columbia University, New York City, noted that these results align with ACR 2021 recommendations. Dr. Bathon was not involved with this study but was on the writing committee establishing those 2021 guidelines.
“The recommendation – with low certainty of evidence – was that for patients who are intolerant to MTX, that split-dose of oral MTX is worth trying before you switch to a different DMARD,” she said. “I think these data support that concept.”
Dr. Dhir and Dr. Bathon had no relevant financial relationships. Dr. Pope disclosed financial relationships with AbbVie/Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Fresenius Kabi, GlaxoSmithKline, Janssen, Mallinckrodt, Novartis, Organon, Pfizer, Sandoz, and Viatris.
A version of this article first appeared on Medscape.com.
SAN DIEGO – A split dose of methotrexate (MTX) given orally once per week showed significantly higher efficacy in patients with rheumatoid arthritis at 16 weeks, compared with a single MTX dose weekly, according to new research. By 24 weeks, efficacy measures were similar for both groups.
However, fewer patients in the split-dose group needed additional disease-modifying antirheumatic drugs (DMARDs) to control disease activity.
MTX is a highly utilized, inexpensive drug for RA, but only about 30% of patients can achieve low disease activity or remission on MTX monotherapy, said Varun Dhir, MD, MBBS, of the Postgraduate Institute of Medical Education and Research, Chandigarh, India. He co-authored and presented the research at the annual meeting of the American College of Rheumatology.
Part of the problem is that “oral methotrexate absorption from the gut reduces as the doses go up,” Dr. Dhir noted, because the transport mechanism gets saturated. MTX delivered subcutaneously is one way to improve efficacy, but patients can be needle-averse, and in some countries, like India, pre-filled syringes are not available, he said.
There is pharmacokinetic data dating back 20 years that suggest split-dose MTX could be more efficacious. “However, there are no randomized controlled trials to date, and the guidelines therefore are silent on this approach,” Dr. Dhir said.
To address this question, Dr. Dhir and colleagues recruited patients with RA from six centers across India. Patients were aged 18-60 years, seropositive (rheumatoid factor or anti-citrullinated protein antibodies), and had a disease duration of 5 years or fewer. Patients had active disease, defined as at least four tender joints and at least two swollen joints, and were not taking any DMARDs except for hydroxychloroquine and/or low-dose prednisolone.
A total of 253 patients were randomly assigned to a single 25-mg dose or a split-dose of MTX once weekly (10 mg in the morning and 15 mg in the evening on the same day). The primary outcome was a European Alliance of Associations for Rheumatology (EULAR) good response at 24 weeks. At the 16-week mark, if patients had not achieved low disease activity based on a 28-joint Disease Activity Score (DAS28) greater than 3.2, a blinded assessor could add either leflunomide or sulfasalazine to the continued MTX therapy.
At baseline, there was no difference between the groups’ DAS28, but after 16 weeks, DAS28 was significantly lower in the split-dose group, compared with the single-dose group (4.4 vs. 5.1; P < .001), and a higher percentage of patients in the split-dose group had a EULAR good response.
About three-quarters (76.6%) of patients in the split-dose group experienced an improvement of at least 20% in ACR response criteria (ACR20), compared with 52% in the single-dose group. The split-dose group also had higher proportion of patients achieving ACR50 and ACR70.
About one-third of the split-dose group (35%) added an additional DMARD at 16 weeks, compared with 54.5% of the single-dose group (P = .005).
After 24 weeks, DAS28 scores remained lower in the split-dose group (4.1 vs. 4.5; P = .03), but there were no other differences in treatment responses. Health Assessment Questionnaire scores were the same between both groups at 16 and 24 weeks.
The primary outcome was not met, although Dr. Dhir noted a flaw in the study design that could have affected the results. By allowing patients to add additional DMARDs at 16 weeks, “there were two factors which were affecting the primary outcome” at 24 weeks, he told this news organization. “I feel there was a robust result at least at 16 weeks.”
While there were no major adverse events, the split-dose group had higher rates of transaminitis (elevated liver enzymes) during the study, and low white blood cell count was higher in the single-dose group at 24 weeks. There was no difference in MTX intolerance between the two groups.
“It looks like [the split-dose group] gets out of the block faster. It’s a faster effect,” although the other group did catch up, Janet Pope, MD, MPH, of Western University, London, Ont., said in an interview. She was not involved with the research. Two positive results were the earlier ACR responses in the split-dose group as well as fewer patients in that same group needing to add another DMARD to therapy.
“In my opinion, if it’s equal cost, why not try it and see?” she said.
In a separate presentation referring to the abstract, Joan Bathon, MD, director of rheumatology at Columbia University, New York City, noted that these results align with ACR 2021 recommendations. Dr. Bathon was not involved with this study but was on the writing committee establishing those 2021 guidelines.
“The recommendation – with low certainty of evidence – was that for patients who are intolerant to MTX, that split-dose of oral MTX is worth trying before you switch to a different DMARD,” she said. “I think these data support that concept.”
Dr. Dhir and Dr. Bathon had no relevant financial relationships. Dr. Pope disclosed financial relationships with AbbVie/Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Fresenius Kabi, GlaxoSmithKline, Janssen, Mallinckrodt, Novartis, Organon, Pfizer, Sandoz, and Viatris.
A version of this article first appeared on Medscape.com.
AT ACR 2023
IV secukinumab, alternative to self-injections, reaches primary endpoints in PsA, axSpA
SAN DIEGO – Monthly use of intravenously administered secukinumab (Cosentyx) proved its efficacy over placebo in treating psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in two industry-sponsored, randomized, double-blinded, phase 3 trials of the drug’s second and newly approved route of administration.
The studies of the human monoclonal antibody secukinumab, an interleukin-17 inhibitor, were presented at the annual meeting of the American College of Rheumatology. A subcutaneously injectable formulation of the drug is available, and the Food and Drug Administration approved the IV form for the conditions in October, although at a recommended lower monthly dose than the new trials examined.
In the PsA trial, 191 patients took IV secukinumab, and 190 took placebo. For the primary endpoint, the percentages who reached at least a 50% improvement in American College of Rheumatology response criteria (ACR 50) at 16 weeks were 31.4% and 6.3%, respectively (P < .0001).
In the axSpA trial, 264 patients took IV secukinumab, and 262 took placebo. The primary endpoint, at least a 40% improvement in Assessment of the Spondyloarthritis International Society response criteria (ASAS 40), was met at 16 weeks by 40.9% and 22.9%, respectively (P < .0001).
“Both studies appear to present clear efficacy of IV route administration of secukinumab with no clear increase in safety signals,” consultant rheumatologist Nicola Goodson, MBChB, PhD, of Aintree University Hospital in Liverpool, England, said in an interview.
“Offering IV administration as an option to patients is helpful,” added Dr. Goodson, who was not involved with the study but is familiar with its findings.
As Dr. Goodson explained, secukinumab “was the first IL [interleukin]-17 inhibitor used to treat spondyloarthropathies, and we have been using subcutaneous secukinumab to treat psoriasis, psoriatic arthritis, and axial spondyloarthritis/ankylosing spondylitis since 2016 in the U.K. Our experience with this medication has been good with similar efficacy to anti-TNF [tumor necrosis factor] therapy in axial spondyloarthritis. The medication is generally well-tolerated, and the subcutaneous pen injection device is easy for patients to use.”
However, IV treatment may speed up onset of action, she said, and it may be useful in situations when compliance is a challenge.
PsA trial details
In the PsA trial, known as INVIGORATE-2, researchers recruited patients who met the CASPAR criteria for active PsA with symptoms for ≥ 6 months, and had ≥ 3 tender joints out of 78 joints and ≥ 3 swollen joints out of 76.
Participants with a mean age of 48, including 55% females, were randomized 1:1 to receive placebo or secukinumab (6 mg/kg at baseline followed by 3 mg/kg every 4 weeks). Those in the placebo group were switched to the same monthly doses of secukinumab at 16 weeks.
“Patients who switched from the placebo had a similar increase of efficacy as the original treated group,” rheumatologist Alan J. Kivitz, MD, of the Altoona Center for Clinical Research, in Duncansville, Penn., said in his presentation at the meeting. Specifically, at 52 weeks, the groups had similar ACR 50 response rates: 58% with secukinumab and 64% with placebo-to-secukinumab.
The fact that patients in the original placebo group who received 3 mg IV doses without 6-mg loading doses achieved ACR response rates similar to those who took secukinumab during the whole trial “could suggest that the IV loading dose may not be required. This would need to be explored in a randomized head-to-head study, but it’s an interesting observation that may reduce costs and exposure to higher doses of medication at the start of treatment,” Dr. Goodson said.
Among the patients who received secukinumab at any point in the study, 63% had a treatment-emergent adverse event, including 5.9% with serious events. One death was reported in the placebo group before week 16. No other deaths were reported.
AxSpA trial details
In the axSpA trial, called INVIGORATE-1, researchers recruited people aged ≥18 years with a diagnosis of active radiographic axSpA according to modified New York criteria or nonradiographic axSpA according to ASAS criteria, and all had inflammatory back pain for ≥6 months with an onset before age 45. They were randomized at a 1:1 ratio to receive IV secukinumab (6 mg/kg loading dose, followed by 3 mg/kg every 4 weeks) or placebo for 16 weeks. At that point, the placebo group switched to the same monthly doses of IV secukinumab.
Participants had a mean age of about 39, and about one-third were female.
Following the statistical superiority in ASAS 40 response rates seen with IV secukinumab at week 16, patients who from there switched from placebo to IV secukinumab achieved comparable ASAS 40 response rates to those of patients originally randomized to secukinumab by week 24, reaching 66.8% for those on secukinumab the whole time and 74.9% for those who switched.
Secondary outcome measures were similar in both groups at week 52.
Among all patients who took secukinumab – the percentage with any adverse event was 63.2%, and 6% had a nonfatal adverse event deemed serious. There was one death during secukinumab treatment not suspected to be related to treatment.
In a presentation about the axSpA study findings, Atul Deodhar, MD, of Oregon Health & Science University, noted that “having an IV biologic available in the U.S. has some advantages. There are certain insurance providers such as Medicare where it is more economical for the patient to have an IV drug available.”
Dr. Deodhar also noted that in October the FDA approved a recommended lower dose for the IV treatment than in the study: 1.75 mg/kg instead of 3 mg/kg following the loading dose. That’s because the 3 mg/kg dose caused blood levels to be higher than those in the subcutaneous form, he said.
The FDA made the same dose recommendation for PsA.
Study limitations
Dr. Goodson, the U.K. consultant rheumatologist, noted a limitation of the trials: “It would have been interesting to compare IV to subcutaneous route secukinumab.” Still, the findings suggest that “the safety and efficacy of IV administration appears comparable,” she said.
“IV administration will have associated costs of attending hospital or infusion clinics,” she added, “and the cost of additional staff and administration need to be considered.”
Novartis, the maker of secukinumab, funded both studies. The PsA study authors report multiple relationships with industry, and some, such as Dr. Kivitz, have connections to Novartis. The axSpA study authors also report multiple relationships with industry, and some, such as Dr. Deodhar, have connections to Novartis. Some authors of both studies are Novartis employees. Dr. Goodson disclosed financial relationships with UCB and AbbVie.
SAN DIEGO – Monthly use of intravenously administered secukinumab (Cosentyx) proved its efficacy over placebo in treating psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in two industry-sponsored, randomized, double-blinded, phase 3 trials of the drug’s second and newly approved route of administration.
The studies of the human monoclonal antibody secukinumab, an interleukin-17 inhibitor, were presented at the annual meeting of the American College of Rheumatology. A subcutaneously injectable formulation of the drug is available, and the Food and Drug Administration approved the IV form for the conditions in October, although at a recommended lower monthly dose than the new trials examined.
In the PsA trial, 191 patients took IV secukinumab, and 190 took placebo. For the primary endpoint, the percentages who reached at least a 50% improvement in American College of Rheumatology response criteria (ACR 50) at 16 weeks were 31.4% and 6.3%, respectively (P < .0001).
In the axSpA trial, 264 patients took IV secukinumab, and 262 took placebo. The primary endpoint, at least a 40% improvement in Assessment of the Spondyloarthritis International Society response criteria (ASAS 40), was met at 16 weeks by 40.9% and 22.9%, respectively (P < .0001).
“Both studies appear to present clear efficacy of IV route administration of secukinumab with no clear increase in safety signals,” consultant rheumatologist Nicola Goodson, MBChB, PhD, of Aintree University Hospital in Liverpool, England, said in an interview.
“Offering IV administration as an option to patients is helpful,” added Dr. Goodson, who was not involved with the study but is familiar with its findings.
As Dr. Goodson explained, secukinumab “was the first IL [interleukin]-17 inhibitor used to treat spondyloarthropathies, and we have been using subcutaneous secukinumab to treat psoriasis, psoriatic arthritis, and axial spondyloarthritis/ankylosing spondylitis since 2016 in the U.K. Our experience with this medication has been good with similar efficacy to anti-TNF [tumor necrosis factor] therapy in axial spondyloarthritis. The medication is generally well-tolerated, and the subcutaneous pen injection device is easy for patients to use.”
However, IV treatment may speed up onset of action, she said, and it may be useful in situations when compliance is a challenge.
PsA trial details
In the PsA trial, known as INVIGORATE-2, researchers recruited patients who met the CASPAR criteria for active PsA with symptoms for ≥ 6 months, and had ≥ 3 tender joints out of 78 joints and ≥ 3 swollen joints out of 76.
Participants with a mean age of 48, including 55% females, were randomized 1:1 to receive placebo or secukinumab (6 mg/kg at baseline followed by 3 mg/kg every 4 weeks). Those in the placebo group were switched to the same monthly doses of secukinumab at 16 weeks.
“Patients who switched from the placebo had a similar increase of efficacy as the original treated group,” rheumatologist Alan J. Kivitz, MD, of the Altoona Center for Clinical Research, in Duncansville, Penn., said in his presentation at the meeting. Specifically, at 52 weeks, the groups had similar ACR 50 response rates: 58% with secukinumab and 64% with placebo-to-secukinumab.
The fact that patients in the original placebo group who received 3 mg IV doses without 6-mg loading doses achieved ACR response rates similar to those who took secukinumab during the whole trial “could suggest that the IV loading dose may not be required. This would need to be explored in a randomized head-to-head study, but it’s an interesting observation that may reduce costs and exposure to higher doses of medication at the start of treatment,” Dr. Goodson said.
Among the patients who received secukinumab at any point in the study, 63% had a treatment-emergent adverse event, including 5.9% with serious events. One death was reported in the placebo group before week 16. No other deaths were reported.
AxSpA trial details
In the axSpA trial, called INVIGORATE-1, researchers recruited people aged ≥18 years with a diagnosis of active radiographic axSpA according to modified New York criteria or nonradiographic axSpA according to ASAS criteria, and all had inflammatory back pain for ≥6 months with an onset before age 45. They were randomized at a 1:1 ratio to receive IV secukinumab (6 mg/kg loading dose, followed by 3 mg/kg every 4 weeks) or placebo for 16 weeks. At that point, the placebo group switched to the same monthly doses of IV secukinumab.
Participants had a mean age of about 39, and about one-third were female.
Following the statistical superiority in ASAS 40 response rates seen with IV secukinumab at week 16, patients who from there switched from placebo to IV secukinumab achieved comparable ASAS 40 response rates to those of patients originally randomized to secukinumab by week 24, reaching 66.8% for those on secukinumab the whole time and 74.9% for those who switched.
Secondary outcome measures were similar in both groups at week 52.
Among all patients who took secukinumab – the percentage with any adverse event was 63.2%, and 6% had a nonfatal adverse event deemed serious. There was one death during secukinumab treatment not suspected to be related to treatment.
In a presentation about the axSpA study findings, Atul Deodhar, MD, of Oregon Health & Science University, noted that “having an IV biologic available in the U.S. has some advantages. There are certain insurance providers such as Medicare where it is more economical for the patient to have an IV drug available.”
Dr. Deodhar also noted that in October the FDA approved a recommended lower dose for the IV treatment than in the study: 1.75 mg/kg instead of 3 mg/kg following the loading dose. That’s because the 3 mg/kg dose caused blood levels to be higher than those in the subcutaneous form, he said.
The FDA made the same dose recommendation for PsA.
Study limitations
Dr. Goodson, the U.K. consultant rheumatologist, noted a limitation of the trials: “It would have been interesting to compare IV to subcutaneous route secukinumab.” Still, the findings suggest that “the safety and efficacy of IV administration appears comparable,” she said.
“IV administration will have associated costs of attending hospital or infusion clinics,” she added, “and the cost of additional staff and administration need to be considered.”
Novartis, the maker of secukinumab, funded both studies. The PsA study authors report multiple relationships with industry, and some, such as Dr. Kivitz, have connections to Novartis. The axSpA study authors also report multiple relationships with industry, and some, such as Dr. Deodhar, have connections to Novartis. Some authors of both studies are Novartis employees. Dr. Goodson disclosed financial relationships with UCB and AbbVie.
SAN DIEGO – Monthly use of intravenously administered secukinumab (Cosentyx) proved its efficacy over placebo in treating psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in two industry-sponsored, randomized, double-blinded, phase 3 trials of the drug’s second and newly approved route of administration.
The studies of the human monoclonal antibody secukinumab, an interleukin-17 inhibitor, were presented at the annual meeting of the American College of Rheumatology. A subcutaneously injectable formulation of the drug is available, and the Food and Drug Administration approved the IV form for the conditions in October, although at a recommended lower monthly dose than the new trials examined.
In the PsA trial, 191 patients took IV secukinumab, and 190 took placebo. For the primary endpoint, the percentages who reached at least a 50% improvement in American College of Rheumatology response criteria (ACR 50) at 16 weeks were 31.4% and 6.3%, respectively (P < .0001).
In the axSpA trial, 264 patients took IV secukinumab, and 262 took placebo. The primary endpoint, at least a 40% improvement in Assessment of the Spondyloarthritis International Society response criteria (ASAS 40), was met at 16 weeks by 40.9% and 22.9%, respectively (P < .0001).
“Both studies appear to present clear efficacy of IV route administration of secukinumab with no clear increase in safety signals,” consultant rheumatologist Nicola Goodson, MBChB, PhD, of Aintree University Hospital in Liverpool, England, said in an interview.
“Offering IV administration as an option to patients is helpful,” added Dr. Goodson, who was not involved with the study but is familiar with its findings.
As Dr. Goodson explained, secukinumab “was the first IL [interleukin]-17 inhibitor used to treat spondyloarthropathies, and we have been using subcutaneous secukinumab to treat psoriasis, psoriatic arthritis, and axial spondyloarthritis/ankylosing spondylitis since 2016 in the U.K. Our experience with this medication has been good with similar efficacy to anti-TNF [tumor necrosis factor] therapy in axial spondyloarthritis. The medication is generally well-tolerated, and the subcutaneous pen injection device is easy for patients to use.”
However, IV treatment may speed up onset of action, she said, and it may be useful in situations when compliance is a challenge.
PsA trial details
In the PsA trial, known as INVIGORATE-2, researchers recruited patients who met the CASPAR criteria for active PsA with symptoms for ≥ 6 months, and had ≥ 3 tender joints out of 78 joints and ≥ 3 swollen joints out of 76.
Participants with a mean age of 48, including 55% females, were randomized 1:1 to receive placebo or secukinumab (6 mg/kg at baseline followed by 3 mg/kg every 4 weeks). Those in the placebo group were switched to the same monthly doses of secukinumab at 16 weeks.
“Patients who switched from the placebo had a similar increase of efficacy as the original treated group,” rheumatologist Alan J. Kivitz, MD, of the Altoona Center for Clinical Research, in Duncansville, Penn., said in his presentation at the meeting. Specifically, at 52 weeks, the groups had similar ACR 50 response rates: 58% with secukinumab and 64% with placebo-to-secukinumab.
The fact that patients in the original placebo group who received 3 mg IV doses without 6-mg loading doses achieved ACR response rates similar to those who took secukinumab during the whole trial “could suggest that the IV loading dose may not be required. This would need to be explored in a randomized head-to-head study, but it’s an interesting observation that may reduce costs and exposure to higher doses of medication at the start of treatment,” Dr. Goodson said.
Among the patients who received secukinumab at any point in the study, 63% had a treatment-emergent adverse event, including 5.9% with serious events. One death was reported in the placebo group before week 16. No other deaths were reported.
AxSpA trial details
In the axSpA trial, called INVIGORATE-1, researchers recruited people aged ≥18 years with a diagnosis of active radiographic axSpA according to modified New York criteria or nonradiographic axSpA according to ASAS criteria, and all had inflammatory back pain for ≥6 months with an onset before age 45. They were randomized at a 1:1 ratio to receive IV secukinumab (6 mg/kg loading dose, followed by 3 mg/kg every 4 weeks) or placebo for 16 weeks. At that point, the placebo group switched to the same monthly doses of IV secukinumab.
Participants had a mean age of about 39, and about one-third were female.
Following the statistical superiority in ASAS 40 response rates seen with IV secukinumab at week 16, patients who from there switched from placebo to IV secukinumab achieved comparable ASAS 40 response rates to those of patients originally randomized to secukinumab by week 24, reaching 66.8% for those on secukinumab the whole time and 74.9% for those who switched.
Secondary outcome measures were similar in both groups at week 52.
Among all patients who took secukinumab – the percentage with any adverse event was 63.2%, and 6% had a nonfatal adverse event deemed serious. There was one death during secukinumab treatment not suspected to be related to treatment.
In a presentation about the axSpA study findings, Atul Deodhar, MD, of Oregon Health & Science University, noted that “having an IV biologic available in the U.S. has some advantages. There are certain insurance providers such as Medicare where it is more economical for the patient to have an IV drug available.”
Dr. Deodhar also noted that in October the FDA approved a recommended lower dose for the IV treatment than in the study: 1.75 mg/kg instead of 3 mg/kg following the loading dose. That’s because the 3 mg/kg dose caused blood levels to be higher than those in the subcutaneous form, he said.
The FDA made the same dose recommendation for PsA.
Study limitations
Dr. Goodson, the U.K. consultant rheumatologist, noted a limitation of the trials: “It would have been interesting to compare IV to subcutaneous route secukinumab.” Still, the findings suggest that “the safety and efficacy of IV administration appears comparable,” she said.
“IV administration will have associated costs of attending hospital or infusion clinics,” she added, “and the cost of additional staff and administration need to be considered.”
Novartis, the maker of secukinumab, funded both studies. The PsA study authors report multiple relationships with industry, and some, such as Dr. Kivitz, have connections to Novartis. The axSpA study authors also report multiple relationships with industry, and some, such as Dr. Deodhar, have connections to Novartis. Some authors of both studies are Novartis employees. Dr. Goodson disclosed financial relationships with UCB and AbbVie.
AT ACR 2023
Fibromyalgia, CFS more prevalent in patients with IBS
TOPLINE:
METHODOLOGY:
- The authors conducted a retrospective cohort study to investigate the prevalence and predictors of fibromyalgia and CFS in patients hospitalized with IBS vs people without IBS.
- The researchers used ICD-10 codes to analyze U.S. National Inpatient Sample (NIS) data from 2016-2019.
- A subgroup analysis investigated associations with IBS-diarrhea (IBS-D), IBS-constipation (IBS-C), and IBS-mixed types.
- Variables included patient age, sex, ethnicity, race, household income, insurance status, and hospital-level characteristics (including location, bed size, and teaching status).
TAKEAWAY:
- Among 1.2 million patients with IBS included in the study, 10.7% also had fibromyalgia and 0.4% had CFS. The majority of fibromyalgia (96.5%) and CFS (89.9%) patients were female and White (86.5%). CFS prevalence also was highest among White persons (90.7%).
- The prevalence of fibromyalgia and CFS was significantly higher in patients with IBS compared to those without IBS (adjusted odds ratio [AOR], 5.33 for fibromyalgia and AOR, 5.4 for CFS).
- IBS-D, IBS-C, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS.
- Independent predictors of increased odds of fibromyalgia and CFS, respectively, were increasing age (AOR, 1.02 for both), female sex (AOR, 11.2; AOR, 1.86) and White race (AOR, 2.04; AOR, 1.69).
- Overall, White race, lower socioeconomic status, smoking, alcohol use, obesity, and hyperlipidemia were associated with increased odds of fibromyalgia. For CFS, increased odds were associated with White race, higher socioeconomic status, smoking, obesity, and hyperlipidemia.
IN PRACTICE:
“In current clinical practice, there is a high risk of neglecting multi-syndromic patients. We as clinicians should integrate in our practice with regular screening for other somatic disorders in the IBS population and determine the need to consult other specialties like rheumatology and psychiatry to improve the overall health outcome in IBS patients,” the authors wrote.
SOURCE:
Zahid Ijaz Tarar, MD, University of Missouri, Columbia, led the study, which was published online in Biomedicines.
LIMITATIONS:
The retrospective design of the study can only show associations, not a causal relationship. Lack of blinding and randomization in the data creates bias. The NIS database does not provide medication and laboratory data, so the effect of pharmaceutical therapies cannot be measured.
DISCLOSURES:
The research received no external funding. The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article.
TOPLINE:
METHODOLOGY:
- The authors conducted a retrospective cohort study to investigate the prevalence and predictors of fibromyalgia and CFS in patients hospitalized with IBS vs people without IBS.
- The researchers used ICD-10 codes to analyze U.S. National Inpatient Sample (NIS) data from 2016-2019.
- A subgroup analysis investigated associations with IBS-diarrhea (IBS-D), IBS-constipation (IBS-C), and IBS-mixed types.
- Variables included patient age, sex, ethnicity, race, household income, insurance status, and hospital-level characteristics (including location, bed size, and teaching status).
TAKEAWAY:
- Among 1.2 million patients with IBS included in the study, 10.7% also had fibromyalgia and 0.4% had CFS. The majority of fibromyalgia (96.5%) and CFS (89.9%) patients were female and White (86.5%). CFS prevalence also was highest among White persons (90.7%).
- The prevalence of fibromyalgia and CFS was significantly higher in patients with IBS compared to those without IBS (adjusted odds ratio [AOR], 5.33 for fibromyalgia and AOR, 5.4 for CFS).
- IBS-D, IBS-C, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS.
- Independent predictors of increased odds of fibromyalgia and CFS, respectively, were increasing age (AOR, 1.02 for both), female sex (AOR, 11.2; AOR, 1.86) and White race (AOR, 2.04; AOR, 1.69).
- Overall, White race, lower socioeconomic status, smoking, alcohol use, obesity, and hyperlipidemia were associated with increased odds of fibromyalgia. For CFS, increased odds were associated with White race, higher socioeconomic status, smoking, obesity, and hyperlipidemia.
IN PRACTICE:
“In current clinical practice, there is a high risk of neglecting multi-syndromic patients. We as clinicians should integrate in our practice with regular screening for other somatic disorders in the IBS population and determine the need to consult other specialties like rheumatology and psychiatry to improve the overall health outcome in IBS patients,” the authors wrote.
SOURCE:
Zahid Ijaz Tarar, MD, University of Missouri, Columbia, led the study, which was published online in Biomedicines.
LIMITATIONS:
The retrospective design of the study can only show associations, not a causal relationship. Lack of blinding and randomization in the data creates bias. The NIS database does not provide medication and laboratory data, so the effect of pharmaceutical therapies cannot be measured.
DISCLOSURES:
The research received no external funding. The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article.
TOPLINE:
METHODOLOGY:
- The authors conducted a retrospective cohort study to investigate the prevalence and predictors of fibromyalgia and CFS in patients hospitalized with IBS vs people without IBS.
- The researchers used ICD-10 codes to analyze U.S. National Inpatient Sample (NIS) data from 2016-2019.
- A subgroup analysis investigated associations with IBS-diarrhea (IBS-D), IBS-constipation (IBS-C), and IBS-mixed types.
- Variables included patient age, sex, ethnicity, race, household income, insurance status, and hospital-level characteristics (including location, bed size, and teaching status).
TAKEAWAY:
- Among 1.2 million patients with IBS included in the study, 10.7% also had fibromyalgia and 0.4% had CFS. The majority of fibromyalgia (96.5%) and CFS (89.9%) patients were female and White (86.5%). CFS prevalence also was highest among White persons (90.7%).
- The prevalence of fibromyalgia and CFS was significantly higher in patients with IBS compared to those without IBS (adjusted odds ratio [AOR], 5.33 for fibromyalgia and AOR, 5.4 for CFS).
- IBS-D, IBS-C, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS.
- Independent predictors of increased odds of fibromyalgia and CFS, respectively, were increasing age (AOR, 1.02 for both), female sex (AOR, 11.2; AOR, 1.86) and White race (AOR, 2.04; AOR, 1.69).
- Overall, White race, lower socioeconomic status, smoking, alcohol use, obesity, and hyperlipidemia were associated with increased odds of fibromyalgia. For CFS, increased odds were associated with White race, higher socioeconomic status, smoking, obesity, and hyperlipidemia.
IN PRACTICE:
“In current clinical practice, there is a high risk of neglecting multi-syndromic patients. We as clinicians should integrate in our practice with regular screening for other somatic disorders in the IBS population and determine the need to consult other specialties like rheumatology and psychiatry to improve the overall health outcome in IBS patients,” the authors wrote.
SOURCE:
Zahid Ijaz Tarar, MD, University of Missouri, Columbia, led the study, which was published online in Biomedicines.
LIMITATIONS:
The retrospective design of the study can only show associations, not a causal relationship. Lack of blinding and randomization in the data creates bias. The NIS database does not provide medication and laboratory data, so the effect of pharmaceutical therapies cannot be measured.
DISCLOSURES:
The research received no external funding. The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article.
First referral guide issued for axial spondyloarthritis
SAN DIEGO – The Spondyloarthritis Research and Treatment Network (SPARTAN) has created the first referral recommendations for axial spondyloarthritis (axSpA).
The draft recommendations use a points scoring system, with the goal that at least one in three patients referred would be diagnosed with axSpA, an inflammatory arthritis that affects the central skeleton and shares a genetic overlap with skin psoriasis, inflammatory bowel disease, and inflammatory eye disease.
Patients with axSpA can wait 10 years after symptom onset to be diagnosed with the condition. There are currently no guidelines to advise clinicians on when to refer to a rheumatologist, and with the rheumatology workforce shortage, “it is impossible for rheumatologists to evaluate the 20% of adults in the U.S. who have chronic back pain,” said Maureen Dubreuil, MD, a rheumatologist at Boston University. She presented the work at the annual meeting of the American College of Rheumatology.
To address this issue, Dr. Dubreuil and colleagues conducted a literature review to determine how predictive different spondyloarthritis features were of eventual axSpA diagnosis. The interdisciplinary team identified 38 studies published before March 2022, and uncovered 28 individual potential features associated with axSpA, including pain sites, family history of axSpA and related conditions, blood markers of inflammation, genetic testing, and imaging findings.
Inflammatory back pain elements had the lower predictive values, with positive likelihood ratios (LR+) ranging from 1.15 to 2.32, while imaging findings were the most predictive (LR+s from 6.40 to 10.02).
Using a Delphi exercise and discrete choice experiments, members narrowed the checklist down to 10 features. These 10 features were assigned points, with a score of 3 points qualifying for a referral of adults 45 years or younger with chronic pain (3 or more months) in the back, hip, or buttock.
Sacroiliitis seen on imaging, either by x-ray or MRI, received the highest score of 3 points. Dr. Dubreuil emphasized that imaging was not required for a referral, but if a patient has received imaging “that shows sacroiliitis, that is sufficient for referral to a rheumatologist,” she said in her presentation.
Elevated erythrocyte sedimentation rate or C-reactive protein, HLA-B27 positivity, and uveitis score 2 points. Inflammatory bowel disease; psoriasis; back pain with good response to NSAIDs; back pain improvement with exercise and not with rest; alternating buttock pain; and family history of axial spondyloarthritis, uveitis, psoriasis, or IBD score 1 point.
Dr. Dubreuil and colleagues expect that these criteria for referral will result in about one in three referred adults aged 45 years or younger with chronic back pain being diagnosed with axSpA. They also say additional research is necessary to understand if these recommendations increase probability of axSpA diagnosis and reduce diagnostic delays.
“We’re now getting to the stage where we are creating this screening tool, but [testing the] performance of the screening tool is going to be the major next step,” said Mark Hwang, MD, of UTHealth Houston in an interview with this news organization. He is a member of SPARTAN but was not involved with authoring the recommendations. “Will the screening tool enhance the ability on the back end to identify axSpA? We don’t know yet.”
Jon Chan, MD, a rheumatologist at the University of British Columbia, Vancouver, agreed that these recommendations “are a good first step,” but that more awareness about axSpA from nonrheumatologists would also be helpful in identifying new axSpA patients. He is also a member of SPARTAN and comoderated with Dr. Hwang the session where the new recommendations were presented. “I think other diseases like rheumatoid arthritis or lupus have a lot more recognition in the nonrheumatology community,” he told this news organization.
Connecting with other health professionals who see a lot of patients with back pain – physiotherapists, chiropractors, and chronic pain physicians – could also be helpful, he added. “A lot of times, patients go straight to a physio and circumvent the doctor,” he said.
Dr. Chan reports success in educating other departments. “I put up a poster in the emergency department saying, ‘If you’re young with back pain and uveitis, you need to be seen by rheumatology,’ and we’ve identified a ton of axSpA patients that way,” he said. “Maybe their uveitis was very mild, but their back pain was quite severe, and no one really clued in.”
Dr. Dubreuil disclosed financial relationships with Amgen, Pfizer, and UCB Pharma. Her abstract coauthors disclosed financial relationships with multiple pharmaceutical companies. Dr. Hwang consults for UCB and has received research support from Janssen. Dr. Chan has relationships with AbbVie/Abbott, Eli Lilly, Janssen, Novartis, and UCB.
SAN DIEGO – The Spondyloarthritis Research and Treatment Network (SPARTAN) has created the first referral recommendations for axial spondyloarthritis (axSpA).
The draft recommendations use a points scoring system, with the goal that at least one in three patients referred would be diagnosed with axSpA, an inflammatory arthritis that affects the central skeleton and shares a genetic overlap with skin psoriasis, inflammatory bowel disease, and inflammatory eye disease.
Patients with axSpA can wait 10 years after symptom onset to be diagnosed with the condition. There are currently no guidelines to advise clinicians on when to refer to a rheumatologist, and with the rheumatology workforce shortage, “it is impossible for rheumatologists to evaluate the 20% of adults in the U.S. who have chronic back pain,” said Maureen Dubreuil, MD, a rheumatologist at Boston University. She presented the work at the annual meeting of the American College of Rheumatology.
To address this issue, Dr. Dubreuil and colleagues conducted a literature review to determine how predictive different spondyloarthritis features were of eventual axSpA diagnosis. The interdisciplinary team identified 38 studies published before March 2022, and uncovered 28 individual potential features associated with axSpA, including pain sites, family history of axSpA and related conditions, blood markers of inflammation, genetic testing, and imaging findings.
Inflammatory back pain elements had the lower predictive values, with positive likelihood ratios (LR+) ranging from 1.15 to 2.32, while imaging findings were the most predictive (LR+s from 6.40 to 10.02).
Using a Delphi exercise and discrete choice experiments, members narrowed the checklist down to 10 features. These 10 features were assigned points, with a score of 3 points qualifying for a referral of adults 45 years or younger with chronic pain (3 or more months) in the back, hip, or buttock.
Sacroiliitis seen on imaging, either by x-ray or MRI, received the highest score of 3 points. Dr. Dubreuil emphasized that imaging was not required for a referral, but if a patient has received imaging “that shows sacroiliitis, that is sufficient for referral to a rheumatologist,” she said in her presentation.
Elevated erythrocyte sedimentation rate or C-reactive protein, HLA-B27 positivity, and uveitis score 2 points. Inflammatory bowel disease; psoriasis; back pain with good response to NSAIDs; back pain improvement with exercise and not with rest; alternating buttock pain; and family history of axial spondyloarthritis, uveitis, psoriasis, or IBD score 1 point.
Dr. Dubreuil and colleagues expect that these criteria for referral will result in about one in three referred adults aged 45 years or younger with chronic back pain being diagnosed with axSpA. They also say additional research is necessary to understand if these recommendations increase probability of axSpA diagnosis and reduce diagnostic delays.
“We’re now getting to the stage where we are creating this screening tool, but [testing the] performance of the screening tool is going to be the major next step,” said Mark Hwang, MD, of UTHealth Houston in an interview with this news organization. He is a member of SPARTAN but was not involved with authoring the recommendations. “Will the screening tool enhance the ability on the back end to identify axSpA? We don’t know yet.”
Jon Chan, MD, a rheumatologist at the University of British Columbia, Vancouver, agreed that these recommendations “are a good first step,” but that more awareness about axSpA from nonrheumatologists would also be helpful in identifying new axSpA patients. He is also a member of SPARTAN and comoderated with Dr. Hwang the session where the new recommendations were presented. “I think other diseases like rheumatoid arthritis or lupus have a lot more recognition in the nonrheumatology community,” he told this news organization.
Connecting with other health professionals who see a lot of patients with back pain – physiotherapists, chiropractors, and chronic pain physicians – could also be helpful, he added. “A lot of times, patients go straight to a physio and circumvent the doctor,” he said.
Dr. Chan reports success in educating other departments. “I put up a poster in the emergency department saying, ‘If you’re young with back pain and uveitis, you need to be seen by rheumatology,’ and we’ve identified a ton of axSpA patients that way,” he said. “Maybe their uveitis was very mild, but their back pain was quite severe, and no one really clued in.”
Dr. Dubreuil disclosed financial relationships with Amgen, Pfizer, and UCB Pharma. Her abstract coauthors disclosed financial relationships with multiple pharmaceutical companies. Dr. Hwang consults for UCB and has received research support from Janssen. Dr. Chan has relationships with AbbVie/Abbott, Eli Lilly, Janssen, Novartis, and UCB.
SAN DIEGO – The Spondyloarthritis Research and Treatment Network (SPARTAN) has created the first referral recommendations for axial spondyloarthritis (axSpA).
The draft recommendations use a points scoring system, with the goal that at least one in three patients referred would be diagnosed with axSpA, an inflammatory arthritis that affects the central skeleton and shares a genetic overlap with skin psoriasis, inflammatory bowel disease, and inflammatory eye disease.
Patients with axSpA can wait 10 years after symptom onset to be diagnosed with the condition. There are currently no guidelines to advise clinicians on when to refer to a rheumatologist, and with the rheumatology workforce shortage, “it is impossible for rheumatologists to evaluate the 20% of adults in the U.S. who have chronic back pain,” said Maureen Dubreuil, MD, a rheumatologist at Boston University. She presented the work at the annual meeting of the American College of Rheumatology.
To address this issue, Dr. Dubreuil and colleagues conducted a literature review to determine how predictive different spondyloarthritis features were of eventual axSpA diagnosis. The interdisciplinary team identified 38 studies published before March 2022, and uncovered 28 individual potential features associated with axSpA, including pain sites, family history of axSpA and related conditions, blood markers of inflammation, genetic testing, and imaging findings.
Inflammatory back pain elements had the lower predictive values, with positive likelihood ratios (LR+) ranging from 1.15 to 2.32, while imaging findings were the most predictive (LR+s from 6.40 to 10.02).
Using a Delphi exercise and discrete choice experiments, members narrowed the checklist down to 10 features. These 10 features were assigned points, with a score of 3 points qualifying for a referral of adults 45 years or younger with chronic pain (3 or more months) in the back, hip, or buttock.
Sacroiliitis seen on imaging, either by x-ray or MRI, received the highest score of 3 points. Dr. Dubreuil emphasized that imaging was not required for a referral, but if a patient has received imaging “that shows sacroiliitis, that is sufficient for referral to a rheumatologist,” she said in her presentation.
Elevated erythrocyte sedimentation rate or C-reactive protein, HLA-B27 positivity, and uveitis score 2 points. Inflammatory bowel disease; psoriasis; back pain with good response to NSAIDs; back pain improvement with exercise and not with rest; alternating buttock pain; and family history of axial spondyloarthritis, uveitis, psoriasis, or IBD score 1 point.
Dr. Dubreuil and colleagues expect that these criteria for referral will result in about one in three referred adults aged 45 years or younger with chronic back pain being diagnosed with axSpA. They also say additional research is necessary to understand if these recommendations increase probability of axSpA diagnosis and reduce diagnostic delays.
“We’re now getting to the stage where we are creating this screening tool, but [testing the] performance of the screening tool is going to be the major next step,” said Mark Hwang, MD, of UTHealth Houston in an interview with this news organization. He is a member of SPARTAN but was not involved with authoring the recommendations. “Will the screening tool enhance the ability on the back end to identify axSpA? We don’t know yet.”
Jon Chan, MD, a rheumatologist at the University of British Columbia, Vancouver, agreed that these recommendations “are a good first step,” but that more awareness about axSpA from nonrheumatologists would also be helpful in identifying new axSpA patients. He is also a member of SPARTAN and comoderated with Dr. Hwang the session where the new recommendations were presented. “I think other diseases like rheumatoid arthritis or lupus have a lot more recognition in the nonrheumatology community,” he told this news organization.
Connecting with other health professionals who see a lot of patients with back pain – physiotherapists, chiropractors, and chronic pain physicians – could also be helpful, he added. “A lot of times, patients go straight to a physio and circumvent the doctor,” he said.
Dr. Chan reports success in educating other departments. “I put up a poster in the emergency department saying, ‘If you’re young with back pain and uveitis, you need to be seen by rheumatology,’ and we’ve identified a ton of axSpA patients that way,” he said. “Maybe their uveitis was very mild, but their back pain was quite severe, and no one really clued in.”
Dr. Dubreuil disclosed financial relationships with Amgen, Pfizer, and UCB Pharma. Her abstract coauthors disclosed financial relationships with multiple pharmaceutical companies. Dr. Hwang consults for UCB and has received research support from Janssen. Dr. Chan has relationships with AbbVie/Abbott, Eli Lilly, Janssen, Novartis, and UCB.
AT ACR 2023