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Obesity in Patients With RA Successfully Managed With Remote Diet, Exercise Intervention
TOPLINE:
A combination of remote, supervised aerobic training, resistance training, and a hypocaloric diet significantly improved cardiovascular risk factors in adults with rheumatoid arthritis (RA) and overweight or obesity.
METHODOLOGY:
- The researchers recruited 24 adults aged 60-80 years with RA who met criteria for overweight or obesity; participants were randomized to a Supervised Weight Loss and Exercise Training (SWET) or Counseling Health as Treatment (CHAT) program for 16 weeks.
- The SWET intervention included remote supervision of aerobic training of 150 minutes/week moderate-to-vigorous intensity, 2 days per week of resistance training, and a hypocaloric diet based on a weight loss goal of 7% of body weight. The CHAT patients served as controls and completed two lifestyle counseling sessions followed by monthly check-ins.
- The primary outcome was change in a composite measure of cardiovascular risk based on metabolic syndrome z-score (MSSc), a continuous weighted score of five metabolic syndrome components: Waist circumference, mean arterial blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol.
TAKEAWAY:
- Both groups showed improvement in the primary outcome of MSSc, with absolute changes from baseline of −1.67 for the SWET group and −1.34 for the CHAT group (P < .01 for both).
- Participants in the SWET group showed significantly more improvement in secondary outcome measures of body weight, fat mass, and disease activity score in 28 joints based on C-reactive protein (DAS28-CRP), as well as greater improvement in patient-reported physical and mental health, physical function, and fatigue, than those in the CHAT group, but the CHAT group improved significantly compared with their baseline.
- The strongest specific effects for the different components of the intervention were those of aerobic training on physical function and fatigue, resistance training on DAS28-CRP, and weight loss on MSSc.
- Neither group experienced significant changes in lean mass, absolute peak V02, unilateral isometric knee extension, or bilateral grip strength.
IN PRACTICE:
“Findings from our study indicate, at a minimum, integrating even 2 hours of healthy lifestyle counseling may improve RA management, let alone demonstrate the substantial impact that can be provided by a comprehensive, remotely supervised lifestyle intervention,” the researchers wrote.
SOURCE:
The lead author on the study was Brian J. Andonian, MD, of Duke University, Durham, North Carolina. The study was published online in ACR Open Rheumatology.
LIMITATIONS:
The small sample size was a limitation of the study findings, as was the lack of blinding and high level of motivation in the CHAT group, who had greater improvements than expected in weight loss and increased physical activity; the study also was conducted during the COVID-19 pandemic, with potential physical and mental effects on participants who tested positive during the study period.
DISCLOSURES:
The study was supported by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Claude D. Pepper Older Americans Independence Center of the US National Institute on Aging.
A version of this article appeared on Medscape.com.
TOPLINE:
A combination of remote, supervised aerobic training, resistance training, and a hypocaloric diet significantly improved cardiovascular risk factors in adults with rheumatoid arthritis (RA) and overweight or obesity.
METHODOLOGY:
- The researchers recruited 24 adults aged 60-80 years with RA who met criteria for overweight or obesity; participants were randomized to a Supervised Weight Loss and Exercise Training (SWET) or Counseling Health as Treatment (CHAT) program for 16 weeks.
- The SWET intervention included remote supervision of aerobic training of 150 minutes/week moderate-to-vigorous intensity, 2 days per week of resistance training, and a hypocaloric diet based on a weight loss goal of 7% of body weight. The CHAT patients served as controls and completed two lifestyle counseling sessions followed by monthly check-ins.
- The primary outcome was change in a composite measure of cardiovascular risk based on metabolic syndrome z-score (MSSc), a continuous weighted score of five metabolic syndrome components: Waist circumference, mean arterial blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol.
TAKEAWAY:
- Both groups showed improvement in the primary outcome of MSSc, with absolute changes from baseline of −1.67 for the SWET group and −1.34 for the CHAT group (P < .01 for both).
- Participants in the SWET group showed significantly more improvement in secondary outcome measures of body weight, fat mass, and disease activity score in 28 joints based on C-reactive protein (DAS28-CRP), as well as greater improvement in patient-reported physical and mental health, physical function, and fatigue, than those in the CHAT group, but the CHAT group improved significantly compared with their baseline.
- The strongest specific effects for the different components of the intervention were those of aerobic training on physical function and fatigue, resistance training on DAS28-CRP, and weight loss on MSSc.
- Neither group experienced significant changes in lean mass, absolute peak V02, unilateral isometric knee extension, or bilateral grip strength.
IN PRACTICE:
“Findings from our study indicate, at a minimum, integrating even 2 hours of healthy lifestyle counseling may improve RA management, let alone demonstrate the substantial impact that can be provided by a comprehensive, remotely supervised lifestyle intervention,” the researchers wrote.
SOURCE:
The lead author on the study was Brian J. Andonian, MD, of Duke University, Durham, North Carolina. The study was published online in ACR Open Rheumatology.
LIMITATIONS:
The small sample size was a limitation of the study findings, as was the lack of blinding and high level of motivation in the CHAT group, who had greater improvements than expected in weight loss and increased physical activity; the study also was conducted during the COVID-19 pandemic, with potential physical and mental effects on participants who tested positive during the study period.
DISCLOSURES:
The study was supported by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Claude D. Pepper Older Americans Independence Center of the US National Institute on Aging.
A version of this article appeared on Medscape.com.
TOPLINE:
A combination of remote, supervised aerobic training, resistance training, and a hypocaloric diet significantly improved cardiovascular risk factors in adults with rheumatoid arthritis (RA) and overweight or obesity.
METHODOLOGY:
- The researchers recruited 24 adults aged 60-80 years with RA who met criteria for overweight or obesity; participants were randomized to a Supervised Weight Loss and Exercise Training (SWET) or Counseling Health as Treatment (CHAT) program for 16 weeks.
- The SWET intervention included remote supervision of aerobic training of 150 minutes/week moderate-to-vigorous intensity, 2 days per week of resistance training, and a hypocaloric diet based on a weight loss goal of 7% of body weight. The CHAT patients served as controls and completed two lifestyle counseling sessions followed by monthly check-ins.
- The primary outcome was change in a composite measure of cardiovascular risk based on metabolic syndrome z-score (MSSc), a continuous weighted score of five metabolic syndrome components: Waist circumference, mean arterial blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol.
TAKEAWAY:
- Both groups showed improvement in the primary outcome of MSSc, with absolute changes from baseline of −1.67 for the SWET group and −1.34 for the CHAT group (P < .01 for both).
- Participants in the SWET group showed significantly more improvement in secondary outcome measures of body weight, fat mass, and disease activity score in 28 joints based on C-reactive protein (DAS28-CRP), as well as greater improvement in patient-reported physical and mental health, physical function, and fatigue, than those in the CHAT group, but the CHAT group improved significantly compared with their baseline.
- The strongest specific effects for the different components of the intervention were those of aerobic training on physical function and fatigue, resistance training on DAS28-CRP, and weight loss on MSSc.
- Neither group experienced significant changes in lean mass, absolute peak V02, unilateral isometric knee extension, or bilateral grip strength.
IN PRACTICE:
“Findings from our study indicate, at a minimum, integrating even 2 hours of healthy lifestyle counseling may improve RA management, let alone demonstrate the substantial impact that can be provided by a comprehensive, remotely supervised lifestyle intervention,” the researchers wrote.
SOURCE:
The lead author on the study was Brian J. Andonian, MD, of Duke University, Durham, North Carolina. The study was published online in ACR Open Rheumatology.
LIMITATIONS:
The small sample size was a limitation of the study findings, as was the lack of blinding and high level of motivation in the CHAT group, who had greater improvements than expected in weight loss and increased physical activity; the study also was conducted during the COVID-19 pandemic, with potential physical and mental effects on participants who tested positive during the study period.
DISCLOSURES:
The study was supported by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Claude D. Pepper Older Americans Independence Center of the US National Institute on Aging.
A version of this article appeared on Medscape.com.
A New Test Could Save Arthritis Patients Time, Money, and Pain. But Will It Be Used?
Erinn Maury, MD, knew Remicade wasn’t the right drug for Patti Schulte, a patient with rheumatoid arthritis the physician saw at her Millersville, Maryland, practice. Schulte’s swollen, painful joints hadn’t responded to Enbrel or Humira, two drugs in the same class.
But the insurer insisted, so Schulte went on Remicade. It didn’t work either.
What’s more, Schulte suffered a severe allergic reaction to the infusion therapy, requiring a heavy dose of prednisone, a steroid with grave side effects if used at high doses for too long.
After 18 months, her insurer finally approved Maury’s drug of choice, Orencia. By then, Schulte’s vertebrae, weakened by prednisone, had started cracking. She was only 60.
It’s also a story of how doctors are steered by pharmacy benefit managers — the middlemen of the drug market — as well as by insurers.
Once people with inflammatory conditions such as rheumatoid arthritis reach a certain stage, the first prescription offered is typically Humira, the best-selling drug in history, and part of a class known as tumor necrosis factor inhibitors, or TNFis, which fail to significantly help about half of the patients who take it.
“We practice rheumatology without any help,” said Vibeke Strand, a rheumatologist and adjunct clinical professor at Stanford. She bemoaned the lack of tools available to choose the right drug while bristling at corporate intervention in the decision. “We are told by the insurer what to prescribe to the patient. After they fail methotrexate, it’s a TNF inhibitor, almost always Humira. And that’s not OK.”
If there’s a shred of hope in this story, it’s that a blood test, PrismRA, may herald an era of improved care for patients with rheumatoid arthritis and other autoimmune conditions. But first, it must be embraced by insurers.
PrismRA employs a predictive model that combines clinical factors, blood tests, and 19 gene patterns to identify the roughly 60% of patients who are very unlikely to respond to a TNFi drug.
Over the past 25 years, drug companies have introduced five new classes of autoimmune drugs. TNFis were the first to market, starting in the late 1990s.
Some 1.3 million Americans have rheumatoid arthritis, a disease in which a person’s immune system attacks their joints, causing crippling pain and, if improperly treated, disfigurement. The newer drugs, mostly so-called biologics, are also used by some of the 25 million or more Americans with other autoimmune diseases, such as lupus, Crohn’s disease, and psoriasis. Typically costing tens of thousands of dollars annually, the drugs are prescribed after a patient fails to respond to older, cheaper drugs like methotrexate.
Until recently, rheumatologists have had few ways to predict which of the new drugs would work best on which patients. Often, “it’s a coin flip whether I prescribe drug A or B,” said Jeffrey Curtis, MD, a rheumatology professor at the University of Alabama-Birmingham.
Yet about 90% of the patients who are given one of these advanced drugs start on a TNFi, although there’s often no reason to think a TNFi will work better than another type.
Under these puzzling circumstances, it’s often the insurer rather than the doctor who chooses the patient’s drug. Insurers lean toward TNFis such as adalimumab, commonly sold as brand name Humira, in part because they get large rebates from manufacturers for using them. Although the size of such payments is a trade secret, AbbVie is said to be offering rebates to insurers of up to 60% of Humira’s price. That has enabled it to control 98.5% of the US adalimumab market, even though it has eight biosimilar competitors.
PrismRA’s developer, Scipher Medicine, has provided more than 26,000 test results, rarely covered by insurance. But on October 15, the Centers for Medicare & Medicaid began reimbursing for the test, and its use is expected to rise. At least two other companies are developing drug-matching tests for patients with rheumatoid arthritis.
Although critics say PrismRA is not always useful, it is likely to be the first in a series of diagnostics anticipated over the next decade that could reduce the time that patients with autoimmune disease suffer on the wrong drug.
Academics, small biotechs, and large pharmaceutical companies are investing in methods to distinguish the biological pathways involved in these diseases and the best way to treat each one. This approach, called precision medicine, has existed for years in cancer medicine, in which it’s routine to test the genetics of patients’ tumors to determine the appropriate drug treatment.
“You wouldn’t give Herceptin to a breast cancer patient without knowing whether her tumor was HER2-positive,” said Costantino Pitzalis, MD, a rheumatology professor at the William Harvey Research Institute in London, England. He was speaking before a well-attended session at an American College of Rheumatology conference in San Diego in November. “Why do we not use biopsies or seek molecular markers in rheumatoid arthritis?”
It’s not only patients and doctors who have a stake in which drugs work best for a given person.
When Remicade failed and Schulte waited for the insurer to approve Orencia, she insisted on keeping her job as an accountant. But as her prednisone-related spinal problems worsened, Schulte was forced to retire, go on Medicaid, and seek disability, something she had always sworn to avoid.
Now taxpayers, rather than the insurer, are covering Schulte’s medical bills, Dr. Maury noted.
Precision medicine hasn’t seemed like a priority for large makers of autoimmune drugs, which presumably have some knowledge of which patients are most likely to benefit from their drugs, because they have tested and sold millions of doses over the years. By offering rebate incentives to insurers, companies like AbbVie, which makes Humira, can guarantee theirs are the drugs of choice with insurers.
“If you were AbbVie,” Dr. Curtis said, “why would you ever want to publish data showing who’s not going to do well on your drug, if, in the absence of the test, everyone will start with your drug first?”
What Testing Could Do
Medicare and commercial insurers haven’t yet set a price for PrismRA, but it could save insurers thousands of dollars a year for each patient it helps, according to Krishna Patel, PharmD, Scipher’s associate director of medical affairs.
“If the test cost $750, I still only need it once, and it costs less than a month of whatever drug is not going to work very well for you,” said Dr. Curtis, a coauthor of some studies of the test. “The economics of a biomarker that’s anything but worthless is pretty favorable because our biologics and targeted drugs are so expensive.”
Patients are enthusiastic about the test because so many have had to take TNFis that didn’t work. Many insurers require patients to try a second TNFi and sometimes a third.
Jen Weaver, a patient advocate and mother of three, got little benefit from hydroxychloroquine, sulfasalazine, methotrexate, and Orencia, a non-TNFi biologic therapy, before finding some relief in another, Actemra. But she was taken off that drug when her white blood cells plunged, and the next three drugs she tried — all TNFis — caused allergic reactions, culminating with an outbreak of pus-filled sores. Another drug, Otezla, eventually seemed to help heal the sores, and she’s been stable on it since in combination with methotrexate, Ms. Weaver said.
“What is needed is to substantially shorten this trial-and-error period for patients,” said Shilpa Venkatachalam, PhD, herself a patient and the director of research operations at the Global Healthy Living Foundation. “There’s a lot of anxiety and frustration, weeks in pain wondering whether a drug is going to work for you and what to do if it doesn’t.” A survey by her group found that 91% of patients worried their medications would stop working. And there is evidence that the longer it takes to resolve arthritis symptoms, the less chance they will ever stop.
How insurers will respond to the availability of tests isn’t clear, partly because the arrival of new biosimilar drugs — essentially generic versions — is making TNFis cheaper for insurance plans. While Humira still dominates, AbbVie has increased rebates to insurers, in effect lowering its cost. Lower prices make the PrismRA test less appealing to insurers because widespread use of the test could cut TNFi prescriptions by up to a third.
However, rheumatologist John B. Boone, MD, in Louisville, Kentucky, found to his surprise that insurers mostly accepted alternative prescriptions for 41 patients whom the test showed unlikely to respond to TNFis as part of a clinical trial. Dr. Boone receives consulting fees from Scipher.
Although the test didn’t guarantee good outcomes, he said, the few patients given TNFis despite the test results almost all did poorly on that regimen.
Scientists from AbbVie, which makes several rheumatology drugs in addition to Humira, presented a study at the San Diego conference examining biomarkers that might show which patients would respond to Rinvoq, a new immune-suppressing drug in a class known as the JAK inhibitors. When asked about its use of precision medicine, AbbVie declined to comment.
Over two decades, Humira has been a blockbuster drug for AbbVie. The company sold more than $3.5 billion worth of Humira in the third quarter of 2023, 36% less than a year ago. Sales of Rinvoq, which AbbVie is marketing as a treatment for patients failed by Humira and its class, jumped 60% to $1.1 billion.
What Patients Want
Shannan O’Hara-Levi, a 38-year-old in Monroe, New York, has been on scores of drugs and supplements since being diagnosed with juvenile arthritis at age 3. She’s been nauseated, fatigued, and short of breath and has suffered allergic reactions, but she says the worst part of it was finding a drug that worked and then losing access because of insurance. This happened shortly after she gave birth to a daughter in 2022 and then endured intense joint pain.
“If I could take a blood test that tells me not to waste months or years of my life — absolutely,” she said. “If I could have started my current drug last fall and saved many months of not being able to engage with my baby on the floor — absolutely.”
This article originally appeared on KFFHealthNews.org. KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF — the independent source for health policy research, polling, and journalism.
Erinn Maury, MD, knew Remicade wasn’t the right drug for Patti Schulte, a patient with rheumatoid arthritis the physician saw at her Millersville, Maryland, practice. Schulte’s swollen, painful joints hadn’t responded to Enbrel or Humira, two drugs in the same class.
But the insurer insisted, so Schulte went on Remicade. It didn’t work either.
What’s more, Schulte suffered a severe allergic reaction to the infusion therapy, requiring a heavy dose of prednisone, a steroid with grave side effects if used at high doses for too long.
After 18 months, her insurer finally approved Maury’s drug of choice, Orencia. By then, Schulte’s vertebrae, weakened by prednisone, had started cracking. She was only 60.
It’s also a story of how doctors are steered by pharmacy benefit managers — the middlemen of the drug market — as well as by insurers.
Once people with inflammatory conditions such as rheumatoid arthritis reach a certain stage, the first prescription offered is typically Humira, the best-selling drug in history, and part of a class known as tumor necrosis factor inhibitors, or TNFis, which fail to significantly help about half of the patients who take it.
“We practice rheumatology without any help,” said Vibeke Strand, a rheumatologist and adjunct clinical professor at Stanford. She bemoaned the lack of tools available to choose the right drug while bristling at corporate intervention in the decision. “We are told by the insurer what to prescribe to the patient. After they fail methotrexate, it’s a TNF inhibitor, almost always Humira. And that’s not OK.”
If there’s a shred of hope in this story, it’s that a blood test, PrismRA, may herald an era of improved care for patients with rheumatoid arthritis and other autoimmune conditions. But first, it must be embraced by insurers.
PrismRA employs a predictive model that combines clinical factors, blood tests, and 19 gene patterns to identify the roughly 60% of patients who are very unlikely to respond to a TNFi drug.
Over the past 25 years, drug companies have introduced five new classes of autoimmune drugs. TNFis were the first to market, starting in the late 1990s.
Some 1.3 million Americans have rheumatoid arthritis, a disease in which a person’s immune system attacks their joints, causing crippling pain and, if improperly treated, disfigurement. The newer drugs, mostly so-called biologics, are also used by some of the 25 million or more Americans with other autoimmune diseases, such as lupus, Crohn’s disease, and psoriasis. Typically costing tens of thousands of dollars annually, the drugs are prescribed after a patient fails to respond to older, cheaper drugs like methotrexate.
Until recently, rheumatologists have had few ways to predict which of the new drugs would work best on which patients. Often, “it’s a coin flip whether I prescribe drug A or B,” said Jeffrey Curtis, MD, a rheumatology professor at the University of Alabama-Birmingham.
Yet about 90% of the patients who are given one of these advanced drugs start on a TNFi, although there’s often no reason to think a TNFi will work better than another type.
Under these puzzling circumstances, it’s often the insurer rather than the doctor who chooses the patient’s drug. Insurers lean toward TNFis such as adalimumab, commonly sold as brand name Humira, in part because they get large rebates from manufacturers for using them. Although the size of such payments is a trade secret, AbbVie is said to be offering rebates to insurers of up to 60% of Humira’s price. That has enabled it to control 98.5% of the US adalimumab market, even though it has eight biosimilar competitors.
PrismRA’s developer, Scipher Medicine, has provided more than 26,000 test results, rarely covered by insurance. But on October 15, the Centers for Medicare & Medicaid began reimbursing for the test, and its use is expected to rise. At least two other companies are developing drug-matching tests for patients with rheumatoid arthritis.
Although critics say PrismRA is not always useful, it is likely to be the first in a series of diagnostics anticipated over the next decade that could reduce the time that patients with autoimmune disease suffer on the wrong drug.
Academics, small biotechs, and large pharmaceutical companies are investing in methods to distinguish the biological pathways involved in these diseases and the best way to treat each one. This approach, called precision medicine, has existed for years in cancer medicine, in which it’s routine to test the genetics of patients’ tumors to determine the appropriate drug treatment.
“You wouldn’t give Herceptin to a breast cancer patient without knowing whether her tumor was HER2-positive,” said Costantino Pitzalis, MD, a rheumatology professor at the William Harvey Research Institute in London, England. He was speaking before a well-attended session at an American College of Rheumatology conference in San Diego in November. “Why do we not use biopsies or seek molecular markers in rheumatoid arthritis?”
It’s not only patients and doctors who have a stake in which drugs work best for a given person.
When Remicade failed and Schulte waited for the insurer to approve Orencia, she insisted on keeping her job as an accountant. But as her prednisone-related spinal problems worsened, Schulte was forced to retire, go on Medicaid, and seek disability, something she had always sworn to avoid.
Now taxpayers, rather than the insurer, are covering Schulte’s medical bills, Dr. Maury noted.
Precision medicine hasn’t seemed like a priority for large makers of autoimmune drugs, which presumably have some knowledge of which patients are most likely to benefit from their drugs, because they have tested and sold millions of doses over the years. By offering rebate incentives to insurers, companies like AbbVie, which makes Humira, can guarantee theirs are the drugs of choice with insurers.
“If you were AbbVie,” Dr. Curtis said, “why would you ever want to publish data showing who’s not going to do well on your drug, if, in the absence of the test, everyone will start with your drug first?”
What Testing Could Do
Medicare and commercial insurers haven’t yet set a price for PrismRA, but it could save insurers thousands of dollars a year for each patient it helps, according to Krishna Patel, PharmD, Scipher’s associate director of medical affairs.
“If the test cost $750, I still only need it once, and it costs less than a month of whatever drug is not going to work very well for you,” said Dr. Curtis, a coauthor of some studies of the test. “The economics of a biomarker that’s anything but worthless is pretty favorable because our biologics and targeted drugs are so expensive.”
Patients are enthusiastic about the test because so many have had to take TNFis that didn’t work. Many insurers require patients to try a second TNFi and sometimes a third.
Jen Weaver, a patient advocate and mother of three, got little benefit from hydroxychloroquine, sulfasalazine, methotrexate, and Orencia, a non-TNFi biologic therapy, before finding some relief in another, Actemra. But she was taken off that drug when her white blood cells plunged, and the next three drugs she tried — all TNFis — caused allergic reactions, culminating with an outbreak of pus-filled sores. Another drug, Otezla, eventually seemed to help heal the sores, and she’s been stable on it since in combination with methotrexate, Ms. Weaver said.
“What is needed is to substantially shorten this trial-and-error period for patients,” said Shilpa Venkatachalam, PhD, herself a patient and the director of research operations at the Global Healthy Living Foundation. “There’s a lot of anxiety and frustration, weeks in pain wondering whether a drug is going to work for you and what to do if it doesn’t.” A survey by her group found that 91% of patients worried their medications would stop working. And there is evidence that the longer it takes to resolve arthritis symptoms, the less chance they will ever stop.
How insurers will respond to the availability of tests isn’t clear, partly because the arrival of new biosimilar drugs — essentially generic versions — is making TNFis cheaper for insurance plans. While Humira still dominates, AbbVie has increased rebates to insurers, in effect lowering its cost. Lower prices make the PrismRA test less appealing to insurers because widespread use of the test could cut TNFi prescriptions by up to a third.
However, rheumatologist John B. Boone, MD, in Louisville, Kentucky, found to his surprise that insurers mostly accepted alternative prescriptions for 41 patients whom the test showed unlikely to respond to TNFis as part of a clinical trial. Dr. Boone receives consulting fees from Scipher.
Although the test didn’t guarantee good outcomes, he said, the few patients given TNFis despite the test results almost all did poorly on that regimen.
Scientists from AbbVie, which makes several rheumatology drugs in addition to Humira, presented a study at the San Diego conference examining biomarkers that might show which patients would respond to Rinvoq, a new immune-suppressing drug in a class known as the JAK inhibitors. When asked about its use of precision medicine, AbbVie declined to comment.
Over two decades, Humira has been a blockbuster drug for AbbVie. The company sold more than $3.5 billion worth of Humira in the third quarter of 2023, 36% less than a year ago. Sales of Rinvoq, which AbbVie is marketing as a treatment for patients failed by Humira and its class, jumped 60% to $1.1 billion.
What Patients Want
Shannan O’Hara-Levi, a 38-year-old in Monroe, New York, has been on scores of drugs and supplements since being diagnosed with juvenile arthritis at age 3. She’s been nauseated, fatigued, and short of breath and has suffered allergic reactions, but she says the worst part of it was finding a drug that worked and then losing access because of insurance. This happened shortly after she gave birth to a daughter in 2022 and then endured intense joint pain.
“If I could take a blood test that tells me not to waste months or years of my life — absolutely,” she said. “If I could have started my current drug last fall and saved many months of not being able to engage with my baby on the floor — absolutely.”
This article originally appeared on KFFHealthNews.org. KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF — the independent source for health policy research, polling, and journalism.
Erinn Maury, MD, knew Remicade wasn’t the right drug for Patti Schulte, a patient with rheumatoid arthritis the physician saw at her Millersville, Maryland, practice. Schulte’s swollen, painful joints hadn’t responded to Enbrel or Humira, two drugs in the same class.
But the insurer insisted, so Schulte went on Remicade. It didn’t work either.
What’s more, Schulte suffered a severe allergic reaction to the infusion therapy, requiring a heavy dose of prednisone, a steroid with grave side effects if used at high doses for too long.
After 18 months, her insurer finally approved Maury’s drug of choice, Orencia. By then, Schulte’s vertebrae, weakened by prednisone, had started cracking. She was only 60.
It’s also a story of how doctors are steered by pharmacy benefit managers — the middlemen of the drug market — as well as by insurers.
Once people with inflammatory conditions such as rheumatoid arthritis reach a certain stage, the first prescription offered is typically Humira, the best-selling drug in history, and part of a class known as tumor necrosis factor inhibitors, or TNFis, which fail to significantly help about half of the patients who take it.
“We practice rheumatology without any help,” said Vibeke Strand, a rheumatologist and adjunct clinical professor at Stanford. She bemoaned the lack of tools available to choose the right drug while bristling at corporate intervention in the decision. “We are told by the insurer what to prescribe to the patient. After they fail methotrexate, it’s a TNF inhibitor, almost always Humira. And that’s not OK.”
If there’s a shred of hope in this story, it’s that a blood test, PrismRA, may herald an era of improved care for patients with rheumatoid arthritis and other autoimmune conditions. But first, it must be embraced by insurers.
PrismRA employs a predictive model that combines clinical factors, blood tests, and 19 gene patterns to identify the roughly 60% of patients who are very unlikely to respond to a TNFi drug.
Over the past 25 years, drug companies have introduced five new classes of autoimmune drugs. TNFis were the first to market, starting in the late 1990s.
Some 1.3 million Americans have rheumatoid arthritis, a disease in which a person’s immune system attacks their joints, causing crippling pain and, if improperly treated, disfigurement. The newer drugs, mostly so-called biologics, are also used by some of the 25 million or more Americans with other autoimmune diseases, such as lupus, Crohn’s disease, and psoriasis. Typically costing tens of thousands of dollars annually, the drugs are prescribed after a patient fails to respond to older, cheaper drugs like methotrexate.
Until recently, rheumatologists have had few ways to predict which of the new drugs would work best on which patients. Often, “it’s a coin flip whether I prescribe drug A or B,” said Jeffrey Curtis, MD, a rheumatology professor at the University of Alabama-Birmingham.
Yet about 90% of the patients who are given one of these advanced drugs start on a TNFi, although there’s often no reason to think a TNFi will work better than another type.
Under these puzzling circumstances, it’s often the insurer rather than the doctor who chooses the patient’s drug. Insurers lean toward TNFis such as adalimumab, commonly sold as brand name Humira, in part because they get large rebates from manufacturers for using them. Although the size of such payments is a trade secret, AbbVie is said to be offering rebates to insurers of up to 60% of Humira’s price. That has enabled it to control 98.5% of the US adalimumab market, even though it has eight biosimilar competitors.
PrismRA’s developer, Scipher Medicine, has provided more than 26,000 test results, rarely covered by insurance. But on October 15, the Centers for Medicare & Medicaid began reimbursing for the test, and its use is expected to rise. At least two other companies are developing drug-matching tests for patients with rheumatoid arthritis.
Although critics say PrismRA is not always useful, it is likely to be the first in a series of diagnostics anticipated over the next decade that could reduce the time that patients with autoimmune disease suffer on the wrong drug.
Academics, small biotechs, and large pharmaceutical companies are investing in methods to distinguish the biological pathways involved in these diseases and the best way to treat each one. This approach, called precision medicine, has existed for years in cancer medicine, in which it’s routine to test the genetics of patients’ tumors to determine the appropriate drug treatment.
“You wouldn’t give Herceptin to a breast cancer patient without knowing whether her tumor was HER2-positive,” said Costantino Pitzalis, MD, a rheumatology professor at the William Harvey Research Institute in London, England. He was speaking before a well-attended session at an American College of Rheumatology conference in San Diego in November. “Why do we not use biopsies or seek molecular markers in rheumatoid arthritis?”
It’s not only patients and doctors who have a stake in which drugs work best for a given person.
When Remicade failed and Schulte waited for the insurer to approve Orencia, she insisted on keeping her job as an accountant. But as her prednisone-related spinal problems worsened, Schulte was forced to retire, go on Medicaid, and seek disability, something she had always sworn to avoid.
Now taxpayers, rather than the insurer, are covering Schulte’s medical bills, Dr. Maury noted.
Precision medicine hasn’t seemed like a priority for large makers of autoimmune drugs, which presumably have some knowledge of which patients are most likely to benefit from their drugs, because they have tested and sold millions of doses over the years. By offering rebate incentives to insurers, companies like AbbVie, which makes Humira, can guarantee theirs are the drugs of choice with insurers.
“If you were AbbVie,” Dr. Curtis said, “why would you ever want to publish data showing who’s not going to do well on your drug, if, in the absence of the test, everyone will start with your drug first?”
What Testing Could Do
Medicare and commercial insurers haven’t yet set a price for PrismRA, but it could save insurers thousands of dollars a year for each patient it helps, according to Krishna Patel, PharmD, Scipher’s associate director of medical affairs.
“If the test cost $750, I still only need it once, and it costs less than a month of whatever drug is not going to work very well for you,” said Dr. Curtis, a coauthor of some studies of the test. “The economics of a biomarker that’s anything but worthless is pretty favorable because our biologics and targeted drugs are so expensive.”
Patients are enthusiastic about the test because so many have had to take TNFis that didn’t work. Many insurers require patients to try a second TNFi and sometimes a third.
Jen Weaver, a patient advocate and mother of three, got little benefit from hydroxychloroquine, sulfasalazine, methotrexate, and Orencia, a non-TNFi biologic therapy, before finding some relief in another, Actemra. But she was taken off that drug when her white blood cells plunged, and the next three drugs she tried — all TNFis — caused allergic reactions, culminating with an outbreak of pus-filled sores. Another drug, Otezla, eventually seemed to help heal the sores, and she’s been stable on it since in combination with methotrexate, Ms. Weaver said.
“What is needed is to substantially shorten this trial-and-error period for patients,” said Shilpa Venkatachalam, PhD, herself a patient and the director of research operations at the Global Healthy Living Foundation. “There’s a lot of anxiety and frustration, weeks in pain wondering whether a drug is going to work for you and what to do if it doesn’t.” A survey by her group found that 91% of patients worried their medications would stop working. And there is evidence that the longer it takes to resolve arthritis symptoms, the less chance they will ever stop.
How insurers will respond to the availability of tests isn’t clear, partly because the arrival of new biosimilar drugs — essentially generic versions — is making TNFis cheaper for insurance plans. While Humira still dominates, AbbVie has increased rebates to insurers, in effect lowering its cost. Lower prices make the PrismRA test less appealing to insurers because widespread use of the test could cut TNFi prescriptions by up to a third.
However, rheumatologist John B. Boone, MD, in Louisville, Kentucky, found to his surprise that insurers mostly accepted alternative prescriptions for 41 patients whom the test showed unlikely to respond to TNFis as part of a clinical trial. Dr. Boone receives consulting fees from Scipher.
Although the test didn’t guarantee good outcomes, he said, the few patients given TNFis despite the test results almost all did poorly on that regimen.
Scientists from AbbVie, which makes several rheumatology drugs in addition to Humira, presented a study at the San Diego conference examining biomarkers that might show which patients would respond to Rinvoq, a new immune-suppressing drug in a class known as the JAK inhibitors. When asked about its use of precision medicine, AbbVie declined to comment.
Over two decades, Humira has been a blockbuster drug for AbbVie. The company sold more than $3.5 billion worth of Humira in the third quarter of 2023, 36% less than a year ago. Sales of Rinvoq, which AbbVie is marketing as a treatment for patients failed by Humira and its class, jumped 60% to $1.1 billion.
What Patients Want
Shannan O’Hara-Levi, a 38-year-old in Monroe, New York, has been on scores of drugs and supplements since being diagnosed with juvenile arthritis at age 3. She’s been nauseated, fatigued, and short of breath and has suffered allergic reactions, but she says the worst part of it was finding a drug that worked and then losing access because of insurance. This happened shortly after she gave birth to a daughter in 2022 and then endured intense joint pain.
“If I could take a blood test that tells me not to waste months or years of my life — absolutely,” she said. “If I could have started my current drug last fall and saved many months of not being able to engage with my baby on the floor — absolutely.”
This article originally appeared on KFFHealthNews.org. KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF — the independent source for health policy research, polling, and journalism.
Researchers making strides to better understand RA-associated interstitial lung disease
SAN DIEGO — Clinically significant interstitial lung disease (ILD) is believed to occur in 5%-10% of patients with rheumatoid arthritis (RA), but robust data are lacking on how to best predict which patients face the highest risk for RA-associated ILD. However, the results of several studies presented at the American College of Rheumatology annual meeting indicate that researchers are making strides in this field of rheumatologic care.
Adding Genetic Factors Improves ILD Risk Prediction
In the realm of risk stratification, Austin M. Wheeler, MD, a rheumatology fellow at the University of Nebraska Medical Center, Omaha, discussed the development and validation of a combined clinical and genetic risk score for ILD. “There is clear and well documented phenotypic and genetic overlap of ILD with idiopathic pulmonary fibrosis (IPF),” Dr. Wheeler said. “A number of clinical risk factors have been described for RA-ILD, including older age, male sex, smoking history, higher disease activity, and seropositivity. There are also well-documented genetic risk factors for RA-ILD. The MUC5B genetic variant is the strongest risk factor for IPF, and it’s been described in RA-ILD as well.”
A recently published study indicated that a genetic risk score without the MUC5B variant improved predictive ability for IPF and interstitial lung abnormalities better than using the MUC5B variant alone, “but no prior attempts have been made at developing a composite genetic risk score in RA-ILD” using both genetic and clinical risk factors, he said.
For the current study, Dr. Wheeler and colleagues drew from 2,386 participants in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry, a multicenter, prospective cohort of US veterans with rheumatologist-diagnosed RA and who fulfilled the 1987 ACR classification criteria. The researchers validated ILD through a systematic review of medical records, including clinical diagnosis of ILD plus either imaging or lung biopsy findings, and collected whole genome data that included 12 single nucleotide polymorphisms (SNPs) previously identified to be associated with risk for RA-ILD. They then used a meta-analytic approach to create pooled associations for each of those respective SNPs using data from the VARA registry participants as well as participants from the past study where the SNPs were first identified. “Those pooled associations were what we used for our effects size within the genetic risk score,” which ended up using five of the SNPs, Dr. Wheeler explained. Next, he and his colleagues combined the genetic risk score with clinical risk factors including age, sex, smoking history, disease activity, and rheumatoid factor (RF) positivity to create their combined risk score.
The mean age of the cohort was 70 years, 89% were male, 78% had a smoking history, and 78% were anti–cyclic citrullinated peptide (CCP) antibody positive. Of the 2,386 participants, 224 (9.4%) had RA-ILD. The full composite risk score had the highest area under the receiver operating curve (AUC) of 0.67, compared with an AUC of 0.623 using the clinical factors alone, 0.651 using the clinical factors plus only the MUC5B variant, and 0.654 using the composite score minus only the MUC5B variant. These AUCs show that “the combined risk score performs better than clinical factors even without the inclusion of the MUC5B variant in the score, which is notable because it supports the importance of further investigation into polygenic risk scores in RA-ILD as there is clearly more at play in a patient’s overall genetic risk,” Dr. Wheeler said.
As an example of the composite score’s ability to discriminate between people with and without RA-ILD, a cutpoint of 0.05 gave a sensitivity of 90.2% and would have eliminated about 25% of the cohort from unnecessary high-resolution CT scans and pulmonary function tests, he said.
“This study demonstrates the potential utility of genetic risk scores in RA-ILD identification and supports further investigation into individual risk stratification and screening,” he concluded. “This isn’t ready for clinical applicability by any means, but I think it serves as a proof of concept of the idea of a genetic risk score in RA-ILD.”
Biomarker Score Investigated
In a separate abstract, Brent Luedders, MD, assistant professor of rheumatology and immunology at the University of Nebraska Medical Center, and colleagues set out to determine if a previously derived biomarker score is associated with prevalent and incident ILD in the same VARA Registry cohort. An abstract presented at the ACR 2022 annual meeting found that a panel derived from IPF peripheral biomarkers was significantly associated with RA-ILD, including matrix metalloproteinase (MMP)-2, -7, and -9, eotaxin, macrophage-derived chemokine (MDC), monocyte chemoattractant protein-1 (MCP-1), fms-like tyrosine kinase 3 ligand (Flt3L) and interleukin-8 (IL-8). For the current analysis, Dr. Luedders and colleagues measured the concentrations of seven biomarkers (MMP-7, MMP-9, eotaxin, MDC, MCP-1, Flt3L, IL-8) from serum/plasma samples collected from VARA’s participants at enrollment to develop a score based on the concentrations of each biomarker.
Baseline characteristics were similar between the groups, although those with prevalent RA-ILD were slightly older than those without ILD, and those who developed incident ILD during follow-up had slightly higher RA disease activity at the time of enrollment. When the researchers examined the association of the biomarker score with prevalent RA-ILD as a continuous measure, they found an adjusted OR of 1.08 for prevalent RA-ILD for each 1-point increase in the biomarker score. “When this was divided into quartiles, we found that the highest quartile of the biomarker score was associated with an adjusted odds ratio of 2.31 for prevalent RA-ILD,” Dr. Luedders said. “We saw a significant P for trend of < .001, suggesting a dose-response relationship, in which higher scores had higher risk.” Similar associations were observed for incident RA-ILD, in which participants with the highest quartile had an adjusted hazard ratio of 2.26 for incident RA-ILD.
The AUC of 0.653 that was obtained with clinical factors did not significantly improve with inclusion of the biomarker score, rising to only 0.669. “In receiver operating characteristic analysis, the addition of the biomarker score to clinical variables (age, sex, race, smoking status, anti-CCP positivity, and RA disease activity by DAS28) did not lead to a significant increase in the area under the curve. Therefore, further work is needed to identify combinations of clinical, biomarker, and other factors to accurately predict which people with RA will develop ILD,” he said.
Dr. Luedders acknowledged certain limitations of the results, including the fact that MMP-2 was not measured in this cohort and thus not included in the score. “This was an observational study with usual care; therefore, the absence of systemic evaluation for ILD may miss early or mild RA-ILD cases,” he added. “Similarly, a male predominance may limit the generalizability, and we have limited information on the RA-ILD pattern.” He concluded that the study results “support the shared pathogenesis of IPF and RA-ILD. However, we found that this score has limited discriminative performance, compared to clinical risk factors alone.”
Drilling Down on ILD Subtypes
In a poster abstract presentation at the meeting, Gregory Campbell McDermott, MD, MPH, a rheumatologist at Brigham and Women’s Hospital, Boston, highlighted results from a study that investigated differences in demographic, serologic, and lifestyle factors for RA-ILD and the major subtypes of RA-ILD: usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). “Historically, RA-ILD has been studied as a single entity, even though we increasingly recognized that there are lots of different subtypes that fall under the umbrella of RA-ILD,” Dr. McDermott said in an interview. “We are also learning that the different subtypes probably have both prognostic and potentially therapeutic implications. For example, the UIP subtype, which is the most fibrotic subtype, has the worst prognosis but also may be a potential target for antifibrotic therapies. We’ve been trying to see if we can identify factors that are associated with specific subtypes, in particular the UIP subtype which has the worst prognosis.”
He and his colleagues examined 208 patients with RA-ILD with a mean age of 51 years and 547 patients with RA but no ILD with a mean age of 49 years from two RA cohorts comprising 3,328 patients: the Mass General Brigham Biobank RA Cohort and the Brigham RA Sequential Study (BRASS). Of the 208 RA-ILD cases, nearly half (48%) were RA-UIP, 18% were RA-NSIP, 8% were organizing pneumonia, 3% were respiratory bronchiolitis-ILD, and 23% were other/indeterminate. After conducting multivariable adjusted analyses, the researchers found that RA-ILD was associated with male sex (OR, 1.58; 95% CI, 1.09-2.23), seropositivity for RF and/or anti-CCP (OR, 2.22; 95% CI, 1.51-3.24) and being an ever smoker (OR, 1.70; 95% CI, 1.13-2.54). Having all three of these risk factors was strongly associated with RA-ILD (OR, 6.04; 95% CI, 2.92-12.47) and with RA-UIP in particular (OR, 7.1). “We found that a lot of the traditional RA-ILD risk factors like male sex, history of smoking, and seropositive status were most strongly associated with a UIP pattern,” Dr. McDermott said. “We think this is a first step in trying to understand how these different ILD subtypes may have different risk factors, pathogenesis, and potentially different treatments, prevention, and screening strategies.”
While clinicians wait for guidelines on systemic autoimmune rheumatic disease-associated ILD that are expected to be published by the ACR in 2024, he added that “we probably shouldn’t screen every single person with RA for ILD, but we need to identify people who have symptoms or findings on clinical exam. This study wasn’t designed to look specifically at who is at high risk, but I think we are moving toward that question: Who is high risk, and who’s asymptomatic [but] may need more screening?”
He pointed out limitations of the study, including its retrospective design and the fact that imaging was done for clinical purposes, “so it’s probably a higher risk group to begin with than the whole RA population,” he said. “We also didn’t have data on RA disease activity or erosions, some of these other measures that we think are important for understanding the full RA disease phenotype in these patients.”
Dr. Wheeler reported having no disclosures. Dr. Luedders reported that his study was supported by the VA, the Rheumatology Research Foundation, and the University of Nebraska Medical Center Mentored Scholars Program. Dr. McDermott reported that his study was supported by the Rheumatology Research Foundation.
SAN DIEGO — Clinically significant interstitial lung disease (ILD) is believed to occur in 5%-10% of patients with rheumatoid arthritis (RA), but robust data are lacking on how to best predict which patients face the highest risk for RA-associated ILD. However, the results of several studies presented at the American College of Rheumatology annual meeting indicate that researchers are making strides in this field of rheumatologic care.
Adding Genetic Factors Improves ILD Risk Prediction
In the realm of risk stratification, Austin M. Wheeler, MD, a rheumatology fellow at the University of Nebraska Medical Center, Omaha, discussed the development and validation of a combined clinical and genetic risk score for ILD. “There is clear and well documented phenotypic and genetic overlap of ILD with idiopathic pulmonary fibrosis (IPF),” Dr. Wheeler said. “A number of clinical risk factors have been described for RA-ILD, including older age, male sex, smoking history, higher disease activity, and seropositivity. There are also well-documented genetic risk factors for RA-ILD. The MUC5B genetic variant is the strongest risk factor for IPF, and it’s been described in RA-ILD as well.”
A recently published study indicated that a genetic risk score without the MUC5B variant improved predictive ability for IPF and interstitial lung abnormalities better than using the MUC5B variant alone, “but no prior attempts have been made at developing a composite genetic risk score in RA-ILD” using both genetic and clinical risk factors, he said.
For the current study, Dr. Wheeler and colleagues drew from 2,386 participants in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry, a multicenter, prospective cohort of US veterans with rheumatologist-diagnosed RA and who fulfilled the 1987 ACR classification criteria. The researchers validated ILD through a systematic review of medical records, including clinical diagnosis of ILD plus either imaging or lung biopsy findings, and collected whole genome data that included 12 single nucleotide polymorphisms (SNPs) previously identified to be associated with risk for RA-ILD. They then used a meta-analytic approach to create pooled associations for each of those respective SNPs using data from the VARA registry participants as well as participants from the past study where the SNPs were first identified. “Those pooled associations were what we used for our effects size within the genetic risk score,” which ended up using five of the SNPs, Dr. Wheeler explained. Next, he and his colleagues combined the genetic risk score with clinical risk factors including age, sex, smoking history, disease activity, and rheumatoid factor (RF) positivity to create their combined risk score.
The mean age of the cohort was 70 years, 89% were male, 78% had a smoking history, and 78% were anti–cyclic citrullinated peptide (CCP) antibody positive. Of the 2,386 participants, 224 (9.4%) had RA-ILD. The full composite risk score had the highest area under the receiver operating curve (AUC) of 0.67, compared with an AUC of 0.623 using the clinical factors alone, 0.651 using the clinical factors plus only the MUC5B variant, and 0.654 using the composite score minus only the MUC5B variant. These AUCs show that “the combined risk score performs better than clinical factors even without the inclusion of the MUC5B variant in the score, which is notable because it supports the importance of further investigation into polygenic risk scores in RA-ILD as there is clearly more at play in a patient’s overall genetic risk,” Dr. Wheeler said.
As an example of the composite score’s ability to discriminate between people with and without RA-ILD, a cutpoint of 0.05 gave a sensitivity of 90.2% and would have eliminated about 25% of the cohort from unnecessary high-resolution CT scans and pulmonary function tests, he said.
“This study demonstrates the potential utility of genetic risk scores in RA-ILD identification and supports further investigation into individual risk stratification and screening,” he concluded. “This isn’t ready for clinical applicability by any means, but I think it serves as a proof of concept of the idea of a genetic risk score in RA-ILD.”
Biomarker Score Investigated
In a separate abstract, Brent Luedders, MD, assistant professor of rheumatology and immunology at the University of Nebraska Medical Center, and colleagues set out to determine if a previously derived biomarker score is associated with prevalent and incident ILD in the same VARA Registry cohort. An abstract presented at the ACR 2022 annual meeting found that a panel derived from IPF peripheral biomarkers was significantly associated with RA-ILD, including matrix metalloproteinase (MMP)-2, -7, and -9, eotaxin, macrophage-derived chemokine (MDC), monocyte chemoattractant protein-1 (MCP-1), fms-like tyrosine kinase 3 ligand (Flt3L) and interleukin-8 (IL-8). For the current analysis, Dr. Luedders and colleagues measured the concentrations of seven biomarkers (MMP-7, MMP-9, eotaxin, MDC, MCP-1, Flt3L, IL-8) from serum/plasma samples collected from VARA’s participants at enrollment to develop a score based on the concentrations of each biomarker.
Baseline characteristics were similar between the groups, although those with prevalent RA-ILD were slightly older than those without ILD, and those who developed incident ILD during follow-up had slightly higher RA disease activity at the time of enrollment. When the researchers examined the association of the biomarker score with prevalent RA-ILD as a continuous measure, they found an adjusted OR of 1.08 for prevalent RA-ILD for each 1-point increase in the biomarker score. “When this was divided into quartiles, we found that the highest quartile of the biomarker score was associated with an adjusted odds ratio of 2.31 for prevalent RA-ILD,” Dr. Luedders said. “We saw a significant P for trend of < .001, suggesting a dose-response relationship, in which higher scores had higher risk.” Similar associations were observed for incident RA-ILD, in which participants with the highest quartile had an adjusted hazard ratio of 2.26 for incident RA-ILD.
The AUC of 0.653 that was obtained with clinical factors did not significantly improve with inclusion of the biomarker score, rising to only 0.669. “In receiver operating characteristic analysis, the addition of the biomarker score to clinical variables (age, sex, race, smoking status, anti-CCP positivity, and RA disease activity by DAS28) did not lead to a significant increase in the area under the curve. Therefore, further work is needed to identify combinations of clinical, biomarker, and other factors to accurately predict which people with RA will develop ILD,” he said.
Dr. Luedders acknowledged certain limitations of the results, including the fact that MMP-2 was not measured in this cohort and thus not included in the score. “This was an observational study with usual care; therefore, the absence of systemic evaluation for ILD may miss early or mild RA-ILD cases,” he added. “Similarly, a male predominance may limit the generalizability, and we have limited information on the RA-ILD pattern.” He concluded that the study results “support the shared pathogenesis of IPF and RA-ILD. However, we found that this score has limited discriminative performance, compared to clinical risk factors alone.”
Drilling Down on ILD Subtypes
In a poster abstract presentation at the meeting, Gregory Campbell McDermott, MD, MPH, a rheumatologist at Brigham and Women’s Hospital, Boston, highlighted results from a study that investigated differences in demographic, serologic, and lifestyle factors for RA-ILD and the major subtypes of RA-ILD: usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). “Historically, RA-ILD has been studied as a single entity, even though we increasingly recognized that there are lots of different subtypes that fall under the umbrella of RA-ILD,” Dr. McDermott said in an interview. “We are also learning that the different subtypes probably have both prognostic and potentially therapeutic implications. For example, the UIP subtype, which is the most fibrotic subtype, has the worst prognosis but also may be a potential target for antifibrotic therapies. We’ve been trying to see if we can identify factors that are associated with specific subtypes, in particular the UIP subtype which has the worst prognosis.”
He and his colleagues examined 208 patients with RA-ILD with a mean age of 51 years and 547 patients with RA but no ILD with a mean age of 49 years from two RA cohorts comprising 3,328 patients: the Mass General Brigham Biobank RA Cohort and the Brigham RA Sequential Study (BRASS). Of the 208 RA-ILD cases, nearly half (48%) were RA-UIP, 18% were RA-NSIP, 8% were organizing pneumonia, 3% were respiratory bronchiolitis-ILD, and 23% were other/indeterminate. After conducting multivariable adjusted analyses, the researchers found that RA-ILD was associated with male sex (OR, 1.58; 95% CI, 1.09-2.23), seropositivity for RF and/or anti-CCP (OR, 2.22; 95% CI, 1.51-3.24) and being an ever smoker (OR, 1.70; 95% CI, 1.13-2.54). Having all three of these risk factors was strongly associated with RA-ILD (OR, 6.04; 95% CI, 2.92-12.47) and with RA-UIP in particular (OR, 7.1). “We found that a lot of the traditional RA-ILD risk factors like male sex, history of smoking, and seropositive status were most strongly associated with a UIP pattern,” Dr. McDermott said. “We think this is a first step in trying to understand how these different ILD subtypes may have different risk factors, pathogenesis, and potentially different treatments, prevention, and screening strategies.”
While clinicians wait for guidelines on systemic autoimmune rheumatic disease-associated ILD that are expected to be published by the ACR in 2024, he added that “we probably shouldn’t screen every single person with RA for ILD, but we need to identify people who have symptoms or findings on clinical exam. This study wasn’t designed to look specifically at who is at high risk, but I think we are moving toward that question: Who is high risk, and who’s asymptomatic [but] may need more screening?”
He pointed out limitations of the study, including its retrospective design and the fact that imaging was done for clinical purposes, “so it’s probably a higher risk group to begin with than the whole RA population,” he said. “We also didn’t have data on RA disease activity or erosions, some of these other measures that we think are important for understanding the full RA disease phenotype in these patients.”
Dr. Wheeler reported having no disclosures. Dr. Luedders reported that his study was supported by the VA, the Rheumatology Research Foundation, and the University of Nebraska Medical Center Mentored Scholars Program. Dr. McDermott reported that his study was supported by the Rheumatology Research Foundation.
SAN DIEGO — Clinically significant interstitial lung disease (ILD) is believed to occur in 5%-10% of patients with rheumatoid arthritis (RA), but robust data are lacking on how to best predict which patients face the highest risk for RA-associated ILD. However, the results of several studies presented at the American College of Rheumatology annual meeting indicate that researchers are making strides in this field of rheumatologic care.
Adding Genetic Factors Improves ILD Risk Prediction
In the realm of risk stratification, Austin M. Wheeler, MD, a rheumatology fellow at the University of Nebraska Medical Center, Omaha, discussed the development and validation of a combined clinical and genetic risk score for ILD. “There is clear and well documented phenotypic and genetic overlap of ILD with idiopathic pulmonary fibrosis (IPF),” Dr. Wheeler said. “A number of clinical risk factors have been described for RA-ILD, including older age, male sex, smoking history, higher disease activity, and seropositivity. There are also well-documented genetic risk factors for RA-ILD. The MUC5B genetic variant is the strongest risk factor for IPF, and it’s been described in RA-ILD as well.”
A recently published study indicated that a genetic risk score without the MUC5B variant improved predictive ability for IPF and interstitial lung abnormalities better than using the MUC5B variant alone, “but no prior attempts have been made at developing a composite genetic risk score in RA-ILD” using both genetic and clinical risk factors, he said.
For the current study, Dr. Wheeler and colleagues drew from 2,386 participants in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry, a multicenter, prospective cohort of US veterans with rheumatologist-diagnosed RA and who fulfilled the 1987 ACR classification criteria. The researchers validated ILD through a systematic review of medical records, including clinical diagnosis of ILD plus either imaging or lung biopsy findings, and collected whole genome data that included 12 single nucleotide polymorphisms (SNPs) previously identified to be associated with risk for RA-ILD. They then used a meta-analytic approach to create pooled associations for each of those respective SNPs using data from the VARA registry participants as well as participants from the past study where the SNPs were first identified. “Those pooled associations were what we used for our effects size within the genetic risk score,” which ended up using five of the SNPs, Dr. Wheeler explained. Next, he and his colleagues combined the genetic risk score with clinical risk factors including age, sex, smoking history, disease activity, and rheumatoid factor (RF) positivity to create their combined risk score.
The mean age of the cohort was 70 years, 89% were male, 78% had a smoking history, and 78% were anti–cyclic citrullinated peptide (CCP) antibody positive. Of the 2,386 participants, 224 (9.4%) had RA-ILD. The full composite risk score had the highest area under the receiver operating curve (AUC) of 0.67, compared with an AUC of 0.623 using the clinical factors alone, 0.651 using the clinical factors plus only the MUC5B variant, and 0.654 using the composite score minus only the MUC5B variant. These AUCs show that “the combined risk score performs better than clinical factors even without the inclusion of the MUC5B variant in the score, which is notable because it supports the importance of further investigation into polygenic risk scores in RA-ILD as there is clearly more at play in a patient’s overall genetic risk,” Dr. Wheeler said.
As an example of the composite score’s ability to discriminate between people with and without RA-ILD, a cutpoint of 0.05 gave a sensitivity of 90.2% and would have eliminated about 25% of the cohort from unnecessary high-resolution CT scans and pulmonary function tests, he said.
“This study demonstrates the potential utility of genetic risk scores in RA-ILD identification and supports further investigation into individual risk stratification and screening,” he concluded. “This isn’t ready for clinical applicability by any means, but I think it serves as a proof of concept of the idea of a genetic risk score in RA-ILD.”
Biomarker Score Investigated
In a separate abstract, Brent Luedders, MD, assistant professor of rheumatology and immunology at the University of Nebraska Medical Center, and colleagues set out to determine if a previously derived biomarker score is associated with prevalent and incident ILD in the same VARA Registry cohort. An abstract presented at the ACR 2022 annual meeting found that a panel derived from IPF peripheral biomarkers was significantly associated with RA-ILD, including matrix metalloproteinase (MMP)-2, -7, and -9, eotaxin, macrophage-derived chemokine (MDC), monocyte chemoattractant protein-1 (MCP-1), fms-like tyrosine kinase 3 ligand (Flt3L) and interleukin-8 (IL-8). For the current analysis, Dr. Luedders and colleagues measured the concentrations of seven biomarkers (MMP-7, MMP-9, eotaxin, MDC, MCP-1, Flt3L, IL-8) from serum/plasma samples collected from VARA’s participants at enrollment to develop a score based on the concentrations of each biomarker.
Baseline characteristics were similar between the groups, although those with prevalent RA-ILD were slightly older than those without ILD, and those who developed incident ILD during follow-up had slightly higher RA disease activity at the time of enrollment. When the researchers examined the association of the biomarker score with prevalent RA-ILD as a continuous measure, they found an adjusted OR of 1.08 for prevalent RA-ILD for each 1-point increase in the biomarker score. “When this was divided into quartiles, we found that the highest quartile of the biomarker score was associated with an adjusted odds ratio of 2.31 for prevalent RA-ILD,” Dr. Luedders said. “We saw a significant P for trend of < .001, suggesting a dose-response relationship, in which higher scores had higher risk.” Similar associations were observed for incident RA-ILD, in which participants with the highest quartile had an adjusted hazard ratio of 2.26 for incident RA-ILD.
The AUC of 0.653 that was obtained with clinical factors did not significantly improve with inclusion of the biomarker score, rising to only 0.669. “In receiver operating characteristic analysis, the addition of the biomarker score to clinical variables (age, sex, race, smoking status, anti-CCP positivity, and RA disease activity by DAS28) did not lead to a significant increase in the area under the curve. Therefore, further work is needed to identify combinations of clinical, biomarker, and other factors to accurately predict which people with RA will develop ILD,” he said.
Dr. Luedders acknowledged certain limitations of the results, including the fact that MMP-2 was not measured in this cohort and thus not included in the score. “This was an observational study with usual care; therefore, the absence of systemic evaluation for ILD may miss early or mild RA-ILD cases,” he added. “Similarly, a male predominance may limit the generalizability, and we have limited information on the RA-ILD pattern.” He concluded that the study results “support the shared pathogenesis of IPF and RA-ILD. However, we found that this score has limited discriminative performance, compared to clinical risk factors alone.”
Drilling Down on ILD Subtypes
In a poster abstract presentation at the meeting, Gregory Campbell McDermott, MD, MPH, a rheumatologist at Brigham and Women’s Hospital, Boston, highlighted results from a study that investigated differences in demographic, serologic, and lifestyle factors for RA-ILD and the major subtypes of RA-ILD: usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). “Historically, RA-ILD has been studied as a single entity, even though we increasingly recognized that there are lots of different subtypes that fall under the umbrella of RA-ILD,” Dr. McDermott said in an interview. “We are also learning that the different subtypes probably have both prognostic and potentially therapeutic implications. For example, the UIP subtype, which is the most fibrotic subtype, has the worst prognosis but also may be a potential target for antifibrotic therapies. We’ve been trying to see if we can identify factors that are associated with specific subtypes, in particular the UIP subtype which has the worst prognosis.”
He and his colleagues examined 208 patients with RA-ILD with a mean age of 51 years and 547 patients with RA but no ILD with a mean age of 49 years from two RA cohorts comprising 3,328 patients: the Mass General Brigham Biobank RA Cohort and the Brigham RA Sequential Study (BRASS). Of the 208 RA-ILD cases, nearly half (48%) were RA-UIP, 18% were RA-NSIP, 8% were organizing pneumonia, 3% were respiratory bronchiolitis-ILD, and 23% were other/indeterminate. After conducting multivariable adjusted analyses, the researchers found that RA-ILD was associated with male sex (OR, 1.58; 95% CI, 1.09-2.23), seropositivity for RF and/or anti-CCP (OR, 2.22; 95% CI, 1.51-3.24) and being an ever smoker (OR, 1.70; 95% CI, 1.13-2.54). Having all three of these risk factors was strongly associated with RA-ILD (OR, 6.04; 95% CI, 2.92-12.47) and with RA-UIP in particular (OR, 7.1). “We found that a lot of the traditional RA-ILD risk factors like male sex, history of smoking, and seropositive status were most strongly associated with a UIP pattern,” Dr. McDermott said. “We think this is a first step in trying to understand how these different ILD subtypes may have different risk factors, pathogenesis, and potentially different treatments, prevention, and screening strategies.”
While clinicians wait for guidelines on systemic autoimmune rheumatic disease-associated ILD that are expected to be published by the ACR in 2024, he added that “we probably shouldn’t screen every single person with RA for ILD, but we need to identify people who have symptoms or findings on clinical exam. This study wasn’t designed to look specifically at who is at high risk, but I think we are moving toward that question: Who is high risk, and who’s asymptomatic [but] may need more screening?”
He pointed out limitations of the study, including its retrospective design and the fact that imaging was done for clinical purposes, “so it’s probably a higher risk group to begin with than the whole RA population,” he said. “We also didn’t have data on RA disease activity or erosions, some of these other measures that we think are important for understanding the full RA disease phenotype in these patients.”
Dr. Wheeler reported having no disclosures. Dr. Luedders reported that his study was supported by the VA, the Rheumatology Research Foundation, and the University of Nebraska Medical Center Mentored Scholars Program. Dr. McDermott reported that his study was supported by the Rheumatology Research Foundation.
FROM ACR 2023
Anti-Rheumatic Drugs Linked to Reduced Thyroid Disease Incidence
TOPLINE:
Patients with rheumatoid arthritis (RA) in a large Swedish population cohort show a reduced incidence of autoimmune thyroid diseases, such as hypothyroidism or hyperthyroidism, after being diagnosed with RA, with the effect being more pronounced among those treated with disease-modifying anti-rheumatic drugs (DMARDs), particularly TNF-inhibitors.
Although DMARDs are commonly used in the treatment of RA, the drugs are rarely used to treat autoimmune thyroid diseases. The new results support theories raised in previous smaller studies that DMARDs could have a protective effect against thyroid disease.
METHODOLOGY:
- The study involved 13,731 patients with new-onset RA who were listed in the Swedish Rheumatology Quality Register between 2006 and 2018.
- The patients were matched for sex, age, and residential area with up to five reference individuals in the general population of 63,201 comparators.
- Overall, patients with RA were 64.7% female, with a mean age of 59. They were followed up with their matched comparators until the development of autoimmune thyroid disease, death, emigration, or the end of the study period, December 2019.
- The relative risks of autoimmune thyroid disease following a diagnosis of RA and with treatment with DMARDs were compared with those risks in the general population.
- Participants with a non-autoimmune cause for thyroxine prescription were excluded, as were those with an autoimmune thyroid disease at the time of RA diagnosis.
TAKEAWAY:
- Following their RA diagnosis, 321 (2.3%) of patients developed an autoimmune thyroid disease, compared with 1838 (2.9%) in the general population comparators, representing an incidence of 3.7 vs 4.6 per 1000 person-years (hazard ratio [HR], 0.81).
- The lower incidence of autoimmune thyroid disease was more pronounced with longer RA duration. For instance, at 10-14 years after an RA diagnosis, the incidence was 2.9 vs. 4.5 autoimmune thyroid disease events per 1000 person-years, respectively (HR, 0.64).
- The decreased risk of incident autoimmune thyroid disease among RA patients compared with the general population was strongest among patients treated with biologic DMARDs (bDMARD), with an HR of 0.54.
- The reduced incidence of autoimmune thyroid disease with bDMARD use was most pronounced among users of TNF-inhibitors (HR, 0.67).
- The lower incidence of autoimmune thyroid disease following a diagnosis of RA contrasts with previous studies showing an increased risk for thyroid disease associated with RA.
- However, the decreased risk of thyroid disease following bDMARD treatment supports the theory that immunomodulatory treatment could also have an effect of blunting the inflammatory processes that can lead to overt clinical autoimmune thyroid disease.
IN PRACTICE:
“To our knowledge, no previous study has investigated whether the risk of new-onset autoimmune thyroid disease is affected by RA treatment in early RA,” the authors report.
“Our results demonstrate that compared to the general population, patients with RA treated with bDMARDs, TNF-inhibitors in particular, are at decreased risk of developing autoimmune thyroid disease, a finding that calls for replication and may open for drug-repurposing studies,” they note.
SOURCE:
The study was conducted by first author Kristin Waldenlind, PhD, of the Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden, and colleagues. It was published online November 27 in the Journal of Internal Medicine.
LIMITATIONS:
The study lacked details on participants’ thyroid autoantibody and hormone levels.
The presence of autoimmune thyroid disease was determined based on prescriptions for thyroxine, hence the authors cannot exclude the possibility of a lower threshold for thyroxine prescription among patients treated with DMARDs.
Information was not available on potential risk factors for RA and autoimmune thyroid disease that might have introduced confounding, such as smoking or obesity.
DISCLOSURES:
The study received funding from the Swedish Research Council, the Swedish Heart Lung Foundation, Vinnova, and Region Stockholm/Karolinska Institutet (ALF). The authors’ disclosures are detailed in the published study.
A version of this article appeared on Medscape.com.
TOPLINE:
Patients with rheumatoid arthritis (RA) in a large Swedish population cohort show a reduced incidence of autoimmune thyroid diseases, such as hypothyroidism or hyperthyroidism, after being diagnosed with RA, with the effect being more pronounced among those treated with disease-modifying anti-rheumatic drugs (DMARDs), particularly TNF-inhibitors.
Although DMARDs are commonly used in the treatment of RA, the drugs are rarely used to treat autoimmune thyroid diseases. The new results support theories raised in previous smaller studies that DMARDs could have a protective effect against thyroid disease.
METHODOLOGY:
- The study involved 13,731 patients with new-onset RA who were listed in the Swedish Rheumatology Quality Register between 2006 and 2018.
- The patients were matched for sex, age, and residential area with up to five reference individuals in the general population of 63,201 comparators.
- Overall, patients with RA were 64.7% female, with a mean age of 59. They were followed up with their matched comparators until the development of autoimmune thyroid disease, death, emigration, or the end of the study period, December 2019.
- The relative risks of autoimmune thyroid disease following a diagnosis of RA and with treatment with DMARDs were compared with those risks in the general population.
- Participants with a non-autoimmune cause for thyroxine prescription were excluded, as were those with an autoimmune thyroid disease at the time of RA diagnosis.
TAKEAWAY:
- Following their RA diagnosis, 321 (2.3%) of patients developed an autoimmune thyroid disease, compared with 1838 (2.9%) in the general population comparators, representing an incidence of 3.7 vs 4.6 per 1000 person-years (hazard ratio [HR], 0.81).
- The lower incidence of autoimmune thyroid disease was more pronounced with longer RA duration. For instance, at 10-14 years after an RA diagnosis, the incidence was 2.9 vs. 4.5 autoimmune thyroid disease events per 1000 person-years, respectively (HR, 0.64).
- The decreased risk of incident autoimmune thyroid disease among RA patients compared with the general population was strongest among patients treated with biologic DMARDs (bDMARD), with an HR of 0.54.
- The reduced incidence of autoimmune thyroid disease with bDMARD use was most pronounced among users of TNF-inhibitors (HR, 0.67).
- The lower incidence of autoimmune thyroid disease following a diagnosis of RA contrasts with previous studies showing an increased risk for thyroid disease associated with RA.
- However, the decreased risk of thyroid disease following bDMARD treatment supports the theory that immunomodulatory treatment could also have an effect of blunting the inflammatory processes that can lead to overt clinical autoimmune thyroid disease.
IN PRACTICE:
“To our knowledge, no previous study has investigated whether the risk of new-onset autoimmune thyroid disease is affected by RA treatment in early RA,” the authors report.
“Our results demonstrate that compared to the general population, patients with RA treated with bDMARDs, TNF-inhibitors in particular, are at decreased risk of developing autoimmune thyroid disease, a finding that calls for replication and may open for drug-repurposing studies,” they note.
SOURCE:
The study was conducted by first author Kristin Waldenlind, PhD, of the Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden, and colleagues. It was published online November 27 in the Journal of Internal Medicine.
LIMITATIONS:
The study lacked details on participants’ thyroid autoantibody and hormone levels.
The presence of autoimmune thyroid disease was determined based on prescriptions for thyroxine, hence the authors cannot exclude the possibility of a lower threshold for thyroxine prescription among patients treated with DMARDs.
Information was not available on potential risk factors for RA and autoimmune thyroid disease that might have introduced confounding, such as smoking or obesity.
DISCLOSURES:
The study received funding from the Swedish Research Council, the Swedish Heart Lung Foundation, Vinnova, and Region Stockholm/Karolinska Institutet (ALF). The authors’ disclosures are detailed in the published study.
A version of this article appeared on Medscape.com.
TOPLINE:
Patients with rheumatoid arthritis (RA) in a large Swedish population cohort show a reduced incidence of autoimmune thyroid diseases, such as hypothyroidism or hyperthyroidism, after being diagnosed with RA, with the effect being more pronounced among those treated with disease-modifying anti-rheumatic drugs (DMARDs), particularly TNF-inhibitors.
Although DMARDs are commonly used in the treatment of RA, the drugs are rarely used to treat autoimmune thyroid diseases. The new results support theories raised in previous smaller studies that DMARDs could have a protective effect against thyroid disease.
METHODOLOGY:
- The study involved 13,731 patients with new-onset RA who were listed in the Swedish Rheumatology Quality Register between 2006 and 2018.
- The patients were matched for sex, age, and residential area with up to five reference individuals in the general population of 63,201 comparators.
- Overall, patients with RA were 64.7% female, with a mean age of 59. They were followed up with their matched comparators until the development of autoimmune thyroid disease, death, emigration, or the end of the study period, December 2019.
- The relative risks of autoimmune thyroid disease following a diagnosis of RA and with treatment with DMARDs were compared with those risks in the general population.
- Participants with a non-autoimmune cause for thyroxine prescription were excluded, as were those with an autoimmune thyroid disease at the time of RA diagnosis.
TAKEAWAY:
- Following their RA diagnosis, 321 (2.3%) of patients developed an autoimmune thyroid disease, compared with 1838 (2.9%) in the general population comparators, representing an incidence of 3.7 vs 4.6 per 1000 person-years (hazard ratio [HR], 0.81).
- The lower incidence of autoimmune thyroid disease was more pronounced with longer RA duration. For instance, at 10-14 years after an RA diagnosis, the incidence was 2.9 vs. 4.5 autoimmune thyroid disease events per 1000 person-years, respectively (HR, 0.64).
- The decreased risk of incident autoimmune thyroid disease among RA patients compared with the general population was strongest among patients treated with biologic DMARDs (bDMARD), with an HR of 0.54.
- The reduced incidence of autoimmune thyroid disease with bDMARD use was most pronounced among users of TNF-inhibitors (HR, 0.67).
- The lower incidence of autoimmune thyroid disease following a diagnosis of RA contrasts with previous studies showing an increased risk for thyroid disease associated with RA.
- However, the decreased risk of thyroid disease following bDMARD treatment supports the theory that immunomodulatory treatment could also have an effect of blunting the inflammatory processes that can lead to overt clinical autoimmune thyroid disease.
IN PRACTICE:
“To our knowledge, no previous study has investigated whether the risk of new-onset autoimmune thyroid disease is affected by RA treatment in early RA,” the authors report.
“Our results demonstrate that compared to the general population, patients with RA treated with bDMARDs, TNF-inhibitors in particular, are at decreased risk of developing autoimmune thyroid disease, a finding that calls for replication and may open for drug-repurposing studies,” they note.
SOURCE:
The study was conducted by first author Kristin Waldenlind, PhD, of the Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden, and colleagues. It was published online November 27 in the Journal of Internal Medicine.
LIMITATIONS:
The study lacked details on participants’ thyroid autoantibody and hormone levels.
The presence of autoimmune thyroid disease was determined based on prescriptions for thyroxine, hence the authors cannot exclude the possibility of a lower threshold for thyroxine prescription among patients treated with DMARDs.
Information was not available on potential risk factors for RA and autoimmune thyroid disease that might have introduced confounding, such as smoking or obesity.
DISCLOSURES:
The study received funding from the Swedish Research Council, the Swedish Heart Lung Foundation, Vinnova, and Region Stockholm/Karolinska Institutet (ALF). The authors’ disclosures are detailed in the published study.
A version of this article appeared on Medscape.com.
Commentary: RA and Cancer, and Real-World Medication Studies, December 2023
The association of rheumatoid arthritis (RA) with increased cancer risk compared with the general population has long been known, though the balance between risk related to RA disease activity compared with risk related to immunosuppressive medication has not been clear. This increased risk is seen primarily with lymphoma and lung cancer, and prior research has suggested a risk with biological disease-modifying antirheumatic drugs (bDMARD), such as anti–tumor necrosis factor (TNF) agents. Beydon and colleagues performed a cohort study using a French national claims database; they looked at patients seen for at least 1 year with treatment for RA and compared the incidence of cancer by type. In over 257,000 patients, nearly 24,000 cancer cases were found. The most common cancers were breast, colon, lung, and prostate. All-cancer risk was > 1.2 (standardized incidence ratio) compared with those without cancer, higher in men compared with women, and the risk was increased in patients who received conventional synthetic (cs) DMARD, TNF inhibitors (TNFi), abatacept, and rituximab, but not interleukin (IL)-6 inhibitors or Janus kinase inhibitors (JAKi). Given that the risk was most highly associated with exposure to rituximab, this may show a type of bias rendering the study difficult to interpret, as rituximab is considered "safe" in cancer, and treatments such as csDMARD may have been given because they were not contraindicated in patients with cancer. This renders the study’s other results, such as lower risk with JAKi or higher risk with abatacept, hard to interpret.
Hayashi and colleagues performed a "real-world" comparative study using data from the Japanese observational ANSWER registry database to compare effectiveness of different JAKi over 6 months, a question of high interest given the availability of several JAKi currently. Within the database of over 11,000 participants, only 622 patients were exposed to tofacitinib, baricitinib, peficitinib, or upadacitinib, with 361 included in the final analysis due to missing baseline data (later missing data were imputed). Treatment retention rates were similar among all four JAKi, and discontinuation rates due to adverse events and due to lack of efficacy were similar as well. There was no significant difference in Health Assessment Questionnaire (HAQ), Clinical Disease Activity Index (CDAI), or C-reactive protein after 6 months between the four JAKi. Baricitinib had higher rates of CDAI low disease activity and remission at 6 months when used as a first-line biologic/targeted synthetic (b/ts) DMARD. However, this and other specific findings related to individual JAKi may be affected by the relatively small number of patients included and exposed to each JAKi, and the relatively short duration of follow-up (in terms of drug discontinuation), thus countering the initial premise for the study.
Finally, another important real-world study, by Tageldin and colleagues, looked at tapering therapy in the Rheumatoid Arthritis Medication Tapering (RHEUMTAP) cohort of patients with RA in sustained disease remission or low disease activity for at least 6 months on stable medications (infused bDMARD excluded). This 2-year prospective cohort included reducing frequency, reducing dose, and stopping medication according to predefined regimens. Of 131 patients, 40% underwent tapering, with more flares in the taper group over > 400 days of follow-up; flare rates were much higher in those tapering b/tsDMARD compared with csDMARD. Though limited by small numbers in examining the three different tapering groups, this real-world study provides an important counterpoint to the notion that medication can be tapered easily in RA patients doing well. A more stringent definition or longer duration of disease remission may also affect this finding.
The association of rheumatoid arthritis (RA) with increased cancer risk compared with the general population has long been known, though the balance between risk related to RA disease activity compared with risk related to immunosuppressive medication has not been clear. This increased risk is seen primarily with lymphoma and lung cancer, and prior research has suggested a risk with biological disease-modifying antirheumatic drugs (bDMARD), such as anti–tumor necrosis factor (TNF) agents. Beydon and colleagues performed a cohort study using a French national claims database; they looked at patients seen for at least 1 year with treatment for RA and compared the incidence of cancer by type. In over 257,000 patients, nearly 24,000 cancer cases were found. The most common cancers were breast, colon, lung, and prostate. All-cancer risk was > 1.2 (standardized incidence ratio) compared with those without cancer, higher in men compared with women, and the risk was increased in patients who received conventional synthetic (cs) DMARD, TNF inhibitors (TNFi), abatacept, and rituximab, but not interleukin (IL)-6 inhibitors or Janus kinase inhibitors (JAKi). Given that the risk was most highly associated with exposure to rituximab, this may show a type of bias rendering the study difficult to interpret, as rituximab is considered "safe" in cancer, and treatments such as csDMARD may have been given because they were not contraindicated in patients with cancer. This renders the study’s other results, such as lower risk with JAKi or higher risk with abatacept, hard to interpret.
Hayashi and colleagues performed a "real-world" comparative study using data from the Japanese observational ANSWER registry database to compare effectiveness of different JAKi over 6 months, a question of high interest given the availability of several JAKi currently. Within the database of over 11,000 participants, only 622 patients were exposed to tofacitinib, baricitinib, peficitinib, or upadacitinib, with 361 included in the final analysis due to missing baseline data (later missing data were imputed). Treatment retention rates were similar among all four JAKi, and discontinuation rates due to adverse events and due to lack of efficacy were similar as well. There was no significant difference in Health Assessment Questionnaire (HAQ), Clinical Disease Activity Index (CDAI), or C-reactive protein after 6 months between the four JAKi. Baricitinib had higher rates of CDAI low disease activity and remission at 6 months when used as a first-line biologic/targeted synthetic (b/ts) DMARD. However, this and other specific findings related to individual JAKi may be affected by the relatively small number of patients included and exposed to each JAKi, and the relatively short duration of follow-up (in terms of drug discontinuation), thus countering the initial premise for the study.
Finally, another important real-world study, by Tageldin and colleagues, looked at tapering therapy in the Rheumatoid Arthritis Medication Tapering (RHEUMTAP) cohort of patients with RA in sustained disease remission or low disease activity for at least 6 months on stable medications (infused bDMARD excluded). This 2-year prospective cohort included reducing frequency, reducing dose, and stopping medication according to predefined regimens. Of 131 patients, 40% underwent tapering, with more flares in the taper group over > 400 days of follow-up; flare rates were much higher in those tapering b/tsDMARD compared with csDMARD. Though limited by small numbers in examining the three different tapering groups, this real-world study provides an important counterpoint to the notion that medication can be tapered easily in RA patients doing well. A more stringent definition or longer duration of disease remission may also affect this finding.
The association of rheumatoid arthritis (RA) with increased cancer risk compared with the general population has long been known, though the balance between risk related to RA disease activity compared with risk related to immunosuppressive medication has not been clear. This increased risk is seen primarily with lymphoma and lung cancer, and prior research has suggested a risk with biological disease-modifying antirheumatic drugs (bDMARD), such as anti–tumor necrosis factor (TNF) agents. Beydon and colleagues performed a cohort study using a French national claims database; they looked at patients seen for at least 1 year with treatment for RA and compared the incidence of cancer by type. In over 257,000 patients, nearly 24,000 cancer cases were found. The most common cancers were breast, colon, lung, and prostate. All-cancer risk was > 1.2 (standardized incidence ratio) compared with those without cancer, higher in men compared with women, and the risk was increased in patients who received conventional synthetic (cs) DMARD, TNF inhibitors (TNFi), abatacept, and rituximab, but not interleukin (IL)-6 inhibitors or Janus kinase inhibitors (JAKi). Given that the risk was most highly associated with exposure to rituximab, this may show a type of bias rendering the study difficult to interpret, as rituximab is considered "safe" in cancer, and treatments such as csDMARD may have been given because they were not contraindicated in patients with cancer. This renders the study’s other results, such as lower risk with JAKi or higher risk with abatacept, hard to interpret.
Hayashi and colleagues performed a "real-world" comparative study using data from the Japanese observational ANSWER registry database to compare effectiveness of different JAKi over 6 months, a question of high interest given the availability of several JAKi currently. Within the database of over 11,000 participants, only 622 patients were exposed to tofacitinib, baricitinib, peficitinib, or upadacitinib, with 361 included in the final analysis due to missing baseline data (later missing data were imputed). Treatment retention rates were similar among all four JAKi, and discontinuation rates due to adverse events and due to lack of efficacy were similar as well. There was no significant difference in Health Assessment Questionnaire (HAQ), Clinical Disease Activity Index (CDAI), or C-reactive protein after 6 months between the four JAKi. Baricitinib had higher rates of CDAI low disease activity and remission at 6 months when used as a first-line biologic/targeted synthetic (b/ts) DMARD. However, this and other specific findings related to individual JAKi may be affected by the relatively small number of patients included and exposed to each JAKi, and the relatively short duration of follow-up (in terms of drug discontinuation), thus countering the initial premise for the study.
Finally, another important real-world study, by Tageldin and colleagues, looked at tapering therapy in the Rheumatoid Arthritis Medication Tapering (RHEUMTAP) cohort of patients with RA in sustained disease remission or low disease activity for at least 6 months on stable medications (infused bDMARD excluded). This 2-year prospective cohort included reducing frequency, reducing dose, and stopping medication according to predefined regimens. Of 131 patients, 40% underwent tapering, with more flares in the taper group over > 400 days of follow-up; flare rates were much higher in those tapering b/tsDMARD compared with csDMARD. Though limited by small numbers in examining the three different tapering groups, this real-world study provides an important counterpoint to the notion that medication can be tapered easily in RA patients doing well. A more stringent definition or longer duration of disease remission may also affect this finding.
Predictors of SARS-CoV-2 breakthrough infections in RA after booster dose vaccination
Key clinical point: Findings from this real-world study identified the protective and risk factors associated with SARS-CoV-2 breakthrough infections (BI) in patients with rheumatoid arthritis (RA) who had no COVID-19 infection and received the booster dose of anti-SARS-CoV-2 vaccine.
Major finding: Older patients who were age > 50 years (adjusted hazard ratio [aHR] 0.38; P = .004) and patients receiving conventional synthetic disease-modifying antirheumatic drugs (aHR 0.52; P = .021) had a significantly lower risk for BI, whereas patients receiving anti-interleukin 6 receptor (aHR 2.01; P = 0.039) and anti-CD20 (aHR 2.88; P = .011) treatments had ~2 and ~3 times higher risks for BI, respectively.
Study details: This prospective study included participants who had never been diagnosed with SARS-CoV-2 and had received three doses of the anti-SARS-CoV-2 vaccine, of whom 194 had RA and 1002 were control individuals.
Disclosures: This study was supported by the Italian Ministry of Health and other sources. The authors declared no conflicts of interest.
Source: Picchianti-Diamanti A et al. Older age, a high titre of neutralising antibodies and therapy with conventional DMARDs are associated with protection from breakthrough infection in rheumatoid arthritis patients after the booster dose of anti-SARS-CoV-2 vaccine. Vaccines. 2023;11(11):1684 (Nov 2). doi: 10.3390/vaccines11111684
Key clinical point: Findings from this real-world study identified the protective and risk factors associated with SARS-CoV-2 breakthrough infections (BI) in patients with rheumatoid arthritis (RA) who had no COVID-19 infection and received the booster dose of anti-SARS-CoV-2 vaccine.
Major finding: Older patients who were age > 50 years (adjusted hazard ratio [aHR] 0.38; P = .004) and patients receiving conventional synthetic disease-modifying antirheumatic drugs (aHR 0.52; P = .021) had a significantly lower risk for BI, whereas patients receiving anti-interleukin 6 receptor (aHR 2.01; P = 0.039) and anti-CD20 (aHR 2.88; P = .011) treatments had ~2 and ~3 times higher risks for BI, respectively.
Study details: This prospective study included participants who had never been diagnosed with SARS-CoV-2 and had received three doses of the anti-SARS-CoV-2 vaccine, of whom 194 had RA and 1002 were control individuals.
Disclosures: This study was supported by the Italian Ministry of Health and other sources. The authors declared no conflicts of interest.
Source: Picchianti-Diamanti A et al. Older age, a high titre of neutralising antibodies and therapy with conventional DMARDs are associated with protection from breakthrough infection in rheumatoid arthritis patients after the booster dose of anti-SARS-CoV-2 vaccine. Vaccines. 2023;11(11):1684 (Nov 2). doi: 10.3390/vaccines11111684
Key clinical point: Findings from this real-world study identified the protective and risk factors associated with SARS-CoV-2 breakthrough infections (BI) in patients with rheumatoid arthritis (RA) who had no COVID-19 infection and received the booster dose of anti-SARS-CoV-2 vaccine.
Major finding: Older patients who were age > 50 years (adjusted hazard ratio [aHR] 0.38; P = .004) and patients receiving conventional synthetic disease-modifying antirheumatic drugs (aHR 0.52; P = .021) had a significantly lower risk for BI, whereas patients receiving anti-interleukin 6 receptor (aHR 2.01; P = 0.039) and anti-CD20 (aHR 2.88; P = .011) treatments had ~2 and ~3 times higher risks for BI, respectively.
Study details: This prospective study included participants who had never been diagnosed with SARS-CoV-2 and had received three doses of the anti-SARS-CoV-2 vaccine, of whom 194 had RA and 1002 were control individuals.
Disclosures: This study was supported by the Italian Ministry of Health and other sources. The authors declared no conflicts of interest.
Source: Picchianti-Diamanti A et al. Older age, a high titre of neutralising antibodies and therapy with conventional DMARDs are associated with protection from breakthrough infection in rheumatoid arthritis patients after the booster dose of anti-SARS-CoV-2 vaccine. Vaccines. 2023;11(11):1684 (Nov 2). doi: 10.3390/vaccines11111684
Insights on methotrexate safety with combination therapies in early RA
Key clinical point: Patients with early rheumatoid arthritis (RA) had a higher frequency of adverse events (AE) with methotrexate + tociluzumab vs methotrexate + active conventional treatment (ACT), which restricted their ability to tolerate the target dose of 25 mg methotrexate per week.
Major finding: The risk for methotrexate-associated AE was significantly higher (hazard ratio 1.48; 95% CI 1.20-1.84) and the proportion of patients able to tolerate 25 mg methotrexate per week at 24 weeks was significantly lower (odds ratio 0.25; P < .001) in the methotrexate + tocilizumab vs methotrexate + ACT group. However, the risks for methotrexate-associated AE were comparable for methotrexate +ACT and the combinations of methotrexate with other biologics like certolizumab-pegol or abatacept.
Study details: This post hoc analysis of the phase 4 NORD-STAR trial included 812 treatment-naive patients with early RA who were randomly assigned to receive methotrexate in combination with ACT, certolizumab-pegol, abatacept, or tocilizumab.
Disclosures: This study did not receive any specific funding. Some authors declared receiving grants, contracts, payments, honoraria, or consulting fees from or having other ties with various sources.
Source: Lend K et al. Methotrexate safety and efficacy in combination therapies in patients with early rheumatoid arthritis: A post-hoc analysis of a randomized controlled trial (NORD-STAR). Arthritis Rheumatol. 2023 (Oct 17). doi: 10.1002/art.42730
Key clinical point: Patients with early rheumatoid arthritis (RA) had a higher frequency of adverse events (AE) with methotrexate + tociluzumab vs methotrexate + active conventional treatment (ACT), which restricted their ability to tolerate the target dose of 25 mg methotrexate per week.
Major finding: The risk for methotrexate-associated AE was significantly higher (hazard ratio 1.48; 95% CI 1.20-1.84) and the proportion of patients able to tolerate 25 mg methotrexate per week at 24 weeks was significantly lower (odds ratio 0.25; P < .001) in the methotrexate + tocilizumab vs methotrexate + ACT group. However, the risks for methotrexate-associated AE were comparable for methotrexate +ACT and the combinations of methotrexate with other biologics like certolizumab-pegol or abatacept.
Study details: This post hoc analysis of the phase 4 NORD-STAR trial included 812 treatment-naive patients with early RA who were randomly assigned to receive methotrexate in combination with ACT, certolizumab-pegol, abatacept, or tocilizumab.
Disclosures: This study did not receive any specific funding. Some authors declared receiving grants, contracts, payments, honoraria, or consulting fees from or having other ties with various sources.
Source: Lend K et al. Methotrexate safety and efficacy in combination therapies in patients with early rheumatoid arthritis: A post-hoc analysis of a randomized controlled trial (NORD-STAR). Arthritis Rheumatol. 2023 (Oct 17). doi: 10.1002/art.42730
Key clinical point: Patients with early rheumatoid arthritis (RA) had a higher frequency of adverse events (AE) with methotrexate + tociluzumab vs methotrexate + active conventional treatment (ACT), which restricted their ability to tolerate the target dose of 25 mg methotrexate per week.
Major finding: The risk for methotrexate-associated AE was significantly higher (hazard ratio 1.48; 95% CI 1.20-1.84) and the proportion of patients able to tolerate 25 mg methotrexate per week at 24 weeks was significantly lower (odds ratio 0.25; P < .001) in the methotrexate + tocilizumab vs methotrexate + ACT group. However, the risks for methotrexate-associated AE were comparable for methotrexate +ACT and the combinations of methotrexate with other biologics like certolizumab-pegol or abatacept.
Study details: This post hoc analysis of the phase 4 NORD-STAR trial included 812 treatment-naive patients with early RA who were randomly assigned to receive methotrexate in combination with ACT, certolizumab-pegol, abatacept, or tocilizumab.
Disclosures: This study did not receive any specific funding. Some authors declared receiving grants, contracts, payments, honoraria, or consulting fees from or having other ties with various sources.
Source: Lend K et al. Methotrexate safety and efficacy in combination therapies in patients with early rheumatoid arthritis: A post-hoc analysis of a randomized controlled trial (NORD-STAR). Arthritis Rheumatol. 2023 (Oct 17). doi: 10.1002/art.42730
Sustained remission tied to better outcomes than sustained LDA in early RA
Key clinical point: Patients with early rheumatoid arthritis (RA) who achieved disease remission and sustained it for 10 years had significantly lower structural progression and functional impairment than those who continued to have low disease activity (LDA).
Major finding: Patients with sustained remission vs sustained LDA had significantly lower mean 10-year structural progression (van der Heijde-modified Total Sharp Score 4.06 vs 14.59; P < .001) and 10-year functional impairment (Health Assessment Questionnaire Disability Index 0.14 vs 0.53; P < .001) scores.
Study details: This study analyzed the data of 252 patients with early RA from the ESPOIR cohort, of whom 48 patients were in sustained remission and 135 patients had sustained LDA.
Disclosures: The ESPOIR cohort was supported by grants from Merck Sharp & Dohme and other sources. The authors declared no conflicts of interest.
Source: Ruyssen-Witrand A et al. Ten-year radiographic and functional outcomes in rheumatoid arthritis patients in remission compared to patients in low disease activity. Arthritis Res Ther. 2023;25:207 (Oct 20). doi: 10.1186/s13075-023-03176-7
Key clinical point: Patients with early rheumatoid arthritis (RA) who achieved disease remission and sustained it for 10 years had significantly lower structural progression and functional impairment than those who continued to have low disease activity (LDA).
Major finding: Patients with sustained remission vs sustained LDA had significantly lower mean 10-year structural progression (van der Heijde-modified Total Sharp Score 4.06 vs 14.59; P < .001) and 10-year functional impairment (Health Assessment Questionnaire Disability Index 0.14 vs 0.53; P < .001) scores.
Study details: This study analyzed the data of 252 patients with early RA from the ESPOIR cohort, of whom 48 patients were in sustained remission and 135 patients had sustained LDA.
Disclosures: The ESPOIR cohort was supported by grants from Merck Sharp & Dohme and other sources. The authors declared no conflicts of interest.
Source: Ruyssen-Witrand A et al. Ten-year radiographic and functional outcomes in rheumatoid arthritis patients in remission compared to patients in low disease activity. Arthritis Res Ther. 2023;25:207 (Oct 20). doi: 10.1186/s13075-023-03176-7
Key clinical point: Patients with early rheumatoid arthritis (RA) who achieved disease remission and sustained it for 10 years had significantly lower structural progression and functional impairment than those who continued to have low disease activity (LDA).
Major finding: Patients with sustained remission vs sustained LDA had significantly lower mean 10-year structural progression (van der Heijde-modified Total Sharp Score 4.06 vs 14.59; P < .001) and 10-year functional impairment (Health Assessment Questionnaire Disability Index 0.14 vs 0.53; P < .001) scores.
Study details: This study analyzed the data of 252 patients with early RA from the ESPOIR cohort, of whom 48 patients were in sustained remission and 135 patients had sustained LDA.
Disclosures: The ESPOIR cohort was supported by grants from Merck Sharp & Dohme and other sources. The authors declared no conflicts of interest.
Source: Ruyssen-Witrand A et al. Ten-year radiographic and functional outcomes in rheumatoid arthritis patients in remission compared to patients in low disease activity. Arthritis Res Ther. 2023;25:207 (Oct 20). doi: 10.1186/s13075-023-03176-7
Four-fold higher risk for interstitial lung abnormalities in RA patients with a history of smoking
Key clinical point: Rheumatoid arthritis (RA) increased the prevalence of interstitial lung abnormalities (ILA) in participants with a history of smoking, which in turn led to a significant increase in the mortality rate.
Major finding: ILA were ~4 times more prevalent in individuals with a history of smoking who did vs did not have RA (adjusted odds ratio 4.15; 95% CI 2.17-7.97). Among patients with RA and a record of smoking, mortality risk was ~3 times higher in those with ILA or indeterminate ILA findings vs those without ILA (adjusted hazard ratio 2.86; 95% CI 1.33-6.16).
Study details: This cross-sectional prospective study included participants with a current or past history of smoking from the COPDGene cohort, of whom 83 participants had RA and were compared with 8725 individuals without RA.
Disclosures: COPDGene was supported by the US National Heart, Lung, and Blood Institute and others. Several authors declared receiving consulting fees, grant support, research support, or having other ties with various sources.
Source: McDermott GC et al. Prevalence and mortality associations of interstitial lung abnormalities in rheumatoid arthritis within a multicentre prospective cohort of smokers. Rheumatology (Oxford). 2023;62(SI3):SI286-SI295 (Oct 23). doi: 10.1093/rheumatology/kead277
Key clinical point: Rheumatoid arthritis (RA) increased the prevalence of interstitial lung abnormalities (ILA) in participants with a history of smoking, which in turn led to a significant increase in the mortality rate.
Major finding: ILA were ~4 times more prevalent in individuals with a history of smoking who did vs did not have RA (adjusted odds ratio 4.15; 95% CI 2.17-7.97). Among patients with RA and a record of smoking, mortality risk was ~3 times higher in those with ILA or indeterminate ILA findings vs those without ILA (adjusted hazard ratio 2.86; 95% CI 1.33-6.16).
Study details: This cross-sectional prospective study included participants with a current or past history of smoking from the COPDGene cohort, of whom 83 participants had RA and were compared with 8725 individuals without RA.
Disclosures: COPDGene was supported by the US National Heart, Lung, and Blood Institute and others. Several authors declared receiving consulting fees, grant support, research support, or having other ties with various sources.
Source: McDermott GC et al. Prevalence and mortality associations of interstitial lung abnormalities in rheumatoid arthritis within a multicentre prospective cohort of smokers. Rheumatology (Oxford). 2023;62(SI3):SI286-SI295 (Oct 23). doi: 10.1093/rheumatology/kead277
Key clinical point: Rheumatoid arthritis (RA) increased the prevalence of interstitial lung abnormalities (ILA) in participants with a history of smoking, which in turn led to a significant increase in the mortality rate.
Major finding: ILA were ~4 times more prevalent in individuals with a history of smoking who did vs did not have RA (adjusted odds ratio 4.15; 95% CI 2.17-7.97). Among patients with RA and a record of smoking, mortality risk was ~3 times higher in those with ILA or indeterminate ILA findings vs those without ILA (adjusted hazard ratio 2.86; 95% CI 1.33-6.16).
Study details: This cross-sectional prospective study included participants with a current or past history of smoking from the COPDGene cohort, of whom 83 participants had RA and were compared with 8725 individuals without RA.
Disclosures: COPDGene was supported by the US National Heart, Lung, and Blood Institute and others. Several authors declared receiving consulting fees, grant support, research support, or having other ties with various sources.
Source: McDermott GC et al. Prevalence and mortality associations of interstitial lung abnormalities in rheumatoid arthritis within a multicentre prospective cohort of smokers. Rheumatology (Oxford). 2023;62(SI3):SI286-SI295 (Oct 23). doi: 10.1093/rheumatology/kead277
Meta-analysis assesses hepatitis B reactivation risk in anti-IL-6-treated RA
Key clinical point: The risk for hepatitis B virus (HBV) reactivation was substantially high in patients with rheumatoid arthritis (RA) and chronic HBV infection who were treated with anti-interleukin-6 (anti-IL-6), with the risk being ~5 times higher in the absence of antiviral prophylaxis.
Major finding: The HBV reactivation rate was 6.7% in patients with chronic HBV infection, with the value further increasing to 31% in patients without antiviral prophylaxis. In patients with resolved HBV infection, the HBV reactivation rate remained ~0% irrespective of antiviral prophylaxis administration.
Study details: This meta-analysis of 19 studies included 372 anti-IL-6-treated patients with RA who had chronic (n = 41) or resolved (n = 279) HBV infection, of whom 19 patients received antiviral prophylaxis.
Disclosures: This study did not receive any funding. Two authors declared receiving honoraria, speaker fees, or research grants from or participating in advisory boards of various sources.
Source: Katelani S et al. HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6: A systematic review and meta-analysis. Rheumatology (Oxford). 2023;62(SI3):SI252-SI259 (Oct 23). doi: 10.1093/rheumatology/kead243
Key clinical point: The risk for hepatitis B virus (HBV) reactivation was substantially high in patients with rheumatoid arthritis (RA) and chronic HBV infection who were treated with anti-interleukin-6 (anti-IL-6), with the risk being ~5 times higher in the absence of antiviral prophylaxis.
Major finding: The HBV reactivation rate was 6.7% in patients with chronic HBV infection, with the value further increasing to 31% in patients without antiviral prophylaxis. In patients with resolved HBV infection, the HBV reactivation rate remained ~0% irrespective of antiviral prophylaxis administration.
Study details: This meta-analysis of 19 studies included 372 anti-IL-6-treated patients with RA who had chronic (n = 41) or resolved (n = 279) HBV infection, of whom 19 patients received antiviral prophylaxis.
Disclosures: This study did not receive any funding. Two authors declared receiving honoraria, speaker fees, or research grants from or participating in advisory boards of various sources.
Source: Katelani S et al. HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6: A systematic review and meta-analysis. Rheumatology (Oxford). 2023;62(SI3):SI252-SI259 (Oct 23). doi: 10.1093/rheumatology/kead243
Key clinical point: The risk for hepatitis B virus (HBV) reactivation was substantially high in patients with rheumatoid arthritis (RA) and chronic HBV infection who were treated with anti-interleukin-6 (anti-IL-6), with the risk being ~5 times higher in the absence of antiviral prophylaxis.
Major finding: The HBV reactivation rate was 6.7% in patients with chronic HBV infection, with the value further increasing to 31% in patients without antiviral prophylaxis. In patients with resolved HBV infection, the HBV reactivation rate remained ~0% irrespective of antiviral prophylaxis administration.
Study details: This meta-analysis of 19 studies included 372 anti-IL-6-treated patients with RA who had chronic (n = 41) or resolved (n = 279) HBV infection, of whom 19 patients received antiviral prophylaxis.
Disclosures: This study did not receive any funding. Two authors declared receiving honoraria, speaker fees, or research grants from or participating in advisory boards of various sources.
Source: Katelani S et al. HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6: A systematic review and meta-analysis. Rheumatology (Oxford). 2023;62(SI3):SI252-SI259 (Oct 23). doi: 10.1093/rheumatology/kead243