Rheumatology

MANCHESTER, England – Even when C-reactive protein (CRP) levels are normal, patients with seropositive rheumatoid arthritis (RA) could still be experiencing significant disease that persists over time, researchers from University College London have found.

Similar levels of joint erosion and disease activity were observed over a 5-year period; researchers compared patients who had high CRP levels (> 5 mg/L)* with patients whose CRP levels were consistently normal (< 5 mg/L) at the time of an ultrasound-proven disease flare.

“Our data suggests that the phenotype of normal CRP represents at least 5% of our cohort,” Bhavika Sethi, MBChB, reported in a virtual poster presentation at the annual meeting of the British Society for Rheumatology.

“They are more likely to require biologic treatment, and this continues on even though they have equivalent DAS28 [disease activity score in 28 joints] and risk of joint damage” to high-CRP patients, she said.

These patients are a significant minority, Dr. Sethi added, and “we need to think about how we provide care for them and allocate resources.”
 

Diagnostic delay and poor outcomes previously seen

The study is a continuation of a larger project, the corresponding author for the poster, Matthew Hutchinson, MBChB, told this news organization.

A few years ago, Dr. Hutchinson explained, a subset of patients with normal CRP levels during RA flares were identified and were found to be more likely to have experienced diagnostic delay and worse outcomes than did those with high CRP levels.

The aim of the current study was to see whether those findings persisted by longitudinally assessing patient records and seeing what happened 1, 2, and 5 years later. They evaluated 312 patients with seropositive RA, of whom 28 had CRP < 5 mg/L as well as active disease, which was determined on the basis of a DAS28 > 4.5. Of those 28 patients, 16 had persistently low CRP (< 5 mg/L) despite active disease. All patients who were taking tocilizumab were excluded from the study because of its CRP-lowering properties.

“Our project was showing that this group of people exist, trying to characterize them a little better” and that the study serves as a “jumping-off point” for future research, Dr. Hutchinson said.

The study was also conducted to “make people more aware of [patients with normal CRP during flare], because treating clinicians could be falsely reassured by a normal CRP,” he added. “Patients in front of them could actually be undertreated and have worse outcomes if [it is] not picked up,” Dr. Hutchinson suggested.

In comparison with those with high CRP levels, those with normal CRP levels were more likely to be receiving biologic treatment at 5 years (76.6% vs. 44.4%; P =  .0323).

At 5 years, DAS28 was similar (P = .9615) among patients with normal CRP levels and those with high CRP levels, at a median of 2.8 and 3.2, respectively. A similar percentage of patients in these two groups also had joint damage (63.3% vs. 71.4%; P = .7384).
 

Don’t rely only on CRP to diagnose and manage RA flares

“CRP is a generic inflammatory marker in most people,” Dr. Hutchinson said. “In the majority of situations when either there is inflammation or an infection, certainly if it’s systemic infection or inflammation, you will find CRP being elevated on the blood tests.”

For someone presenting with joint pain, high CRP can be a useful indicator that it’s more of an inflammatory process than physical injury, he added. CRP is also frequently used to calculate DAS28 to monitor disease activity.

“This study highlights that CRP may be normal during flares in some people with RA,” Jeffrey A. Sparks, MD, told this news organization.

“These patients may still require advanced therapies and can accrue damage,” the rheumatologist from Brigham and Women’s Hospital and Harvard University, Boston, added.

“Clinicians should not only rely on CRP to diagnose and manage RA flares,” said Dr. Sparks, who was not involved in the study.

The study was independently supported. Dr. Hutchinson and Dr. Sethi report no relevant financial relationships. Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care; he has received research support from Bristol-Myers Squibb and has performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer.

*Correction, 5/9/2023: This article has been updated to correct the units for C-reactive protein from mg/dL to mg/L.

A version of this article first appeared on Medscape.com.

MANCHESTER, England – Even when C-reactive protein (CRP) levels are normal, patients with seropositive rheumatoid arthritis (RA) could still be experiencing significant disease that persists over time, researchers from University College London have found.

Similar levels of joint erosion and disease activity were observed over a 5-year period; researchers compared patients who had high CRP levels (> 5 mg/L)* with patients whose CRP levels were consistently normal (< 5 mg/L) at the time of an ultrasound-proven disease flare.

“Our data suggests that the phenotype of normal CRP represents at least 5% of our cohort,” Bhavika Sethi, MBChB, reported in a virtual poster presentation at the annual meeting of the British Society for Rheumatology.

“They are more likely to require biologic treatment, and this continues on even though they have equivalent DAS28 [disease activity score in 28 joints] and risk of joint damage” to high-CRP patients, she said.

These patients are a significant minority, Dr. Sethi added, and “we need to think about how we provide care for them and allocate resources.”
 

Diagnostic delay and poor outcomes previously seen

The study is a continuation of a larger project, the corresponding author for the poster, Matthew Hutchinson, MBChB, told this news organization.

A few years ago, Dr. Hutchinson explained, a subset of patients with normal CRP levels during RA flares were identified and were found to be more likely to have experienced diagnostic delay and worse outcomes than did those with high CRP levels.

The aim of the current study was to see whether those findings persisted by longitudinally assessing patient records and seeing what happened 1, 2, and 5 years later. They evaluated 312 patients with seropositive RA, of whom 28 had CRP < 5 mg/L as well as active disease, which was determined on the basis of a DAS28 > 4.5. Of those 28 patients, 16 had persistently low CRP (< 5 mg/L) despite active disease. All patients who were taking tocilizumab were excluded from the study because of its CRP-lowering properties.

“Our project was showing that this group of people exist, trying to characterize them a little better” and that the study serves as a “jumping-off point” for future research, Dr. Hutchinson said.

The study was also conducted to “make people more aware of [patients with normal CRP during flare], because treating clinicians could be falsely reassured by a normal CRP,” he added. “Patients in front of them could actually be undertreated and have worse outcomes if [it is] not picked up,” Dr. Hutchinson suggested.

In comparison with those with high CRP levels, those with normal CRP levels were more likely to be receiving biologic treatment at 5 years (76.6% vs. 44.4%; P =  .0323).

At 5 years, DAS28 was similar (P = .9615) among patients with normal CRP levels and those with high CRP levels, at a median of 2.8 and 3.2, respectively. A similar percentage of patients in these two groups also had joint damage (63.3% vs. 71.4%; P = .7384).
 

Don’t rely only on CRP to diagnose and manage RA flares

“CRP is a generic inflammatory marker in most people,” Dr. Hutchinson said. “In the majority of situations when either there is inflammation or an infection, certainly if it’s systemic infection or inflammation, you will find CRP being elevated on the blood tests.”

For someone presenting with joint pain, high CRP can be a useful indicator that it’s more of an inflammatory process than physical injury, he added. CRP is also frequently used to calculate DAS28 to monitor disease activity.

“This study highlights that CRP may be normal during flares in some people with RA,” Jeffrey A. Sparks, MD, told this news organization.

“These patients may still require advanced therapies and can accrue damage,” the rheumatologist from Brigham and Women’s Hospital and Harvard University, Boston, added.

“Clinicians should not only rely on CRP to diagnose and manage RA flares,” said Dr. Sparks, who was not involved in the study.

The study was independently supported. Dr. Hutchinson and Dr. Sethi report no relevant financial relationships. Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care; he has received research support from Bristol-Myers Squibb and has performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer.

*Correction, 5/9/2023: This article has been updated to correct the units for C-reactive protein from mg/dL to mg/L.

A version of this article first appeared on Medscape.com.

MANCHESTER, England – Even when C-reactive protein (CRP) levels are normal, patients with seropositive rheumatoid arthritis (RA) could still be experiencing significant disease that persists over time, researchers from University College London have found.

Similar levels of joint erosion and disease activity were observed over a 5-year period; researchers compared patients who had high CRP levels (> 5 mg/L)* with patients whose CRP levels were consistently normal (< 5 mg/L) at the time of an ultrasound-proven disease flare.

“Our data suggests that the phenotype of normal CRP represents at least 5% of our cohort,” Bhavika Sethi, MBChB, reported in a virtual poster presentation at the annual meeting of the British Society for Rheumatology.

“They are more likely to require biologic treatment, and this continues on even though they have equivalent DAS28 [disease activity score in 28 joints] and risk of joint damage” to high-CRP patients, she said.

These patients are a significant minority, Dr. Sethi added, and “we need to think about how we provide care for them and allocate resources.”
 

Diagnostic delay and poor outcomes previously seen

The study is a continuation of a larger project, the corresponding author for the poster, Matthew Hutchinson, MBChB, told this news organization.

A few years ago, Dr. Hutchinson explained, a subset of patients with normal CRP levels during RA flares were identified and were found to be more likely to have experienced diagnostic delay and worse outcomes than did those with high CRP levels.

The aim of the current study was to see whether those findings persisted by longitudinally assessing patient records and seeing what happened 1, 2, and 5 years later. They evaluated 312 patients with seropositive RA, of whom 28 had CRP < 5 mg/L as well as active disease, which was determined on the basis of a DAS28 > 4.5. Of those 28 patients, 16 had persistently low CRP (< 5 mg/L) despite active disease. All patients who were taking tocilizumab were excluded from the study because of its CRP-lowering properties.

“Our project was showing that this group of people exist, trying to characterize them a little better” and that the study serves as a “jumping-off point” for future research, Dr. Hutchinson said.

The study was also conducted to “make people more aware of [patients with normal CRP during flare], because treating clinicians could be falsely reassured by a normal CRP,” he added. “Patients in front of them could actually be undertreated and have worse outcomes if [it is] not picked up,” Dr. Hutchinson suggested.

In comparison with those with high CRP levels, those with normal CRP levels were more likely to be receiving biologic treatment at 5 years (76.6% vs. 44.4%; P =  .0323).

At 5 years, DAS28 was similar (P = .9615) among patients with normal CRP levels and those with high CRP levels, at a median of 2.8 and 3.2, respectively. A similar percentage of patients in these two groups also had joint damage (63.3% vs. 71.4%; P = .7384).
 

Don’t rely only on CRP to diagnose and manage RA flares

“CRP is a generic inflammatory marker in most people,” Dr. Hutchinson said. “In the majority of situations when either there is inflammation or an infection, certainly if it’s systemic infection or inflammation, you will find CRP being elevated on the blood tests.”

For someone presenting with joint pain, high CRP can be a useful indicator that it’s more of an inflammatory process than physical injury, he added. CRP is also frequently used to calculate DAS28 to monitor disease activity.

“This study highlights that CRP may be normal during flares in some people with RA,” Jeffrey A. Sparks, MD, told this news organization.

“These patients may still require advanced therapies and can accrue damage,” the rheumatologist from Brigham and Women’s Hospital and Harvard University, Boston, added.

“Clinicians should not only rely on CRP to diagnose and manage RA flares,” said Dr. Sparks, who was not involved in the study.

The study was independently supported. Dr. Hutchinson and Dr. Sethi report no relevant financial relationships. Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care; he has received research support from Bristol-Myers Squibb and has performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer.

*Correction, 5/9/2023: This article has been updated to correct the units for C-reactive protein from mg/dL to mg/L.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has granted Fast Track designation for Cabaletta Bio’s cell therapy CABA-201 for the treatment of systemic lupus erythematosus (SLE) and lupus nephritis (LN), the company announced May 1.
 

The FDA cleared Cabaletta to begin a phase 1/2 clinical trial of CABA-201, the statement says, which will be the first trial accessing Cabaletta’s Chimeric Antigen Receptor T cells for Autoimmunity (CARTA) approach. CABA-201, a 4-1BB–containing fully human CD19-CAR T-cell investigational therapy, is designed to target and deplete CD19-positive B cells, “enabling an ‘immune system reset’ with durable remission in patients with SLE,” according to the press release. This news organization previously reported on a small study in Germany, published in Nature Medicine, that also used anti-CD19 CAR T cells to treat five patients with SLE.

Wikimedia Commons/FitzColinGerald/Creative Commons License

This upcoming open-label study will enroll two cohorts containing six patients each. One cohort will be patients with SLE and active LN, and the other will be patients with SLE without renal involvement. The therapy is designed as a one-time infusion and will be administered at a dose of 1.0 x 106 cells/kg.

“We believe the FDA’s decision to grant Fast Track Designation for CABA-201 underscores the unmet need for a treatment that has the potential to provide deep and durable responses for people living with lupus and potentially other autoimmune diseases where B cells contribute to disease,” David J. Chang, MD, chief medical officer of Cabaletta, said in the press release.

FDA Fast Track is a process designed to expedite the development and review of drugs and other therapeutics that treat serious conditions and address unmet medical needs. Companies that receive Fast Track designation for a drug have the opportunity for more frequent meetings and written communication with the FDA about the drug’s development plan and design of clinical trials. The fast-tracked drug can also be eligible for accelerated approval and priority review if relevant criteria are met.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has granted Fast Track designation for Cabaletta Bio’s cell therapy CABA-201 for the treatment of systemic lupus erythematosus (SLE) and lupus nephritis (LN), the company announced May 1.
 

The FDA cleared Cabaletta to begin a phase 1/2 clinical trial of CABA-201, the statement says, which will be the first trial accessing Cabaletta’s Chimeric Antigen Receptor T cells for Autoimmunity (CARTA) approach. CABA-201, a 4-1BB–containing fully human CD19-CAR T-cell investigational therapy, is designed to target and deplete CD19-positive B cells, “enabling an ‘immune system reset’ with durable remission in patients with SLE,” according to the press release. This news organization previously reported on a small study in Germany, published in Nature Medicine, that also used anti-CD19 CAR T cells to treat five patients with SLE.

Wikimedia Commons/FitzColinGerald/Creative Commons License

This upcoming open-label study will enroll two cohorts containing six patients each. One cohort will be patients with SLE and active LN, and the other will be patients with SLE without renal involvement. The therapy is designed as a one-time infusion and will be administered at a dose of 1.0 x 106 cells/kg.

“We believe the FDA’s decision to grant Fast Track Designation for CABA-201 underscores the unmet need for a treatment that has the potential to provide deep and durable responses for people living with lupus and potentially other autoimmune diseases where B cells contribute to disease,” David J. Chang, MD, chief medical officer of Cabaletta, said in the press release.

FDA Fast Track is a process designed to expedite the development and review of drugs and other therapeutics that treat serious conditions and address unmet medical needs. Companies that receive Fast Track designation for a drug have the opportunity for more frequent meetings and written communication with the FDA about the drug’s development plan and design of clinical trials. The fast-tracked drug can also be eligible for accelerated approval and priority review if relevant criteria are met.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has granted Fast Track designation for Cabaletta Bio’s cell therapy CABA-201 for the treatment of systemic lupus erythematosus (SLE) and lupus nephritis (LN), the company announced May 1.
 

The FDA cleared Cabaletta to begin a phase 1/2 clinical trial of CABA-201, the statement says, which will be the first trial accessing Cabaletta’s Chimeric Antigen Receptor T cells for Autoimmunity (CARTA) approach. CABA-201, a 4-1BB–containing fully human CD19-CAR T-cell investigational therapy, is designed to target and deplete CD19-positive B cells, “enabling an ‘immune system reset’ with durable remission in patients with SLE,” according to the press release. This news organization previously reported on a small study in Germany, published in Nature Medicine, that also used anti-CD19 CAR T cells to treat five patients with SLE.

Wikimedia Commons/FitzColinGerald/Creative Commons License

This upcoming open-label study will enroll two cohorts containing six patients each. One cohort will be patients with SLE and active LN, and the other will be patients with SLE without renal involvement. The therapy is designed as a one-time infusion and will be administered at a dose of 1.0 x 106 cells/kg.

“We believe the FDA’s decision to grant Fast Track Designation for CABA-201 underscores the unmet need for a treatment that has the potential to provide deep and durable responses for people living with lupus and potentially other autoimmune diseases where B cells contribute to disease,” David J. Chang, MD, chief medical officer of Cabaletta, said in the press release.

FDA Fast Track is a process designed to expedite the development and review of drugs and other therapeutics that treat serious conditions and address unmet medical needs. Companies that receive Fast Track designation for a drug have the opportunity for more frequent meetings and written communication with the FDA about the drug’s development plan and design of clinical trials. The fast-tracked drug can also be eligible for accelerated approval and priority review if relevant criteria are met.

A version of this article first appeared on Medscape.com.

MANCHESTER, England – Data from the COVAD-2 e-survey suggest that people with a rheumatic disease are twice as likely as are those without to experience long-term effects after contracting COVID-19.

The prevalence of post–COVID-19 condition (PCC), the term the World Health Organization advocates for describing the widely popularized term long COVID, was 10.8% among people with autoimmune rheumatic diseases (AIRDs) vs. 5.3% among those with no autoimmune condition (designated as “healthy controls”). The odds ratio was 2.1, with a 95% confidence interval of 1.4-3.2 and a P-value of .002.

The prevalence in people with nonrheumatic autoimmune diseases was also higher than it was in the control participants but still lower, at 7.3%, than in those with AIRDs.

Sara Freeman/MDedge News

“Our findings highlight the importance of close monitoring for PCC,” Arvind Nune, MBBCh, MSc, said in a virtual poster presentation at the annual meeting of the British Society for Rheumatology.

They also show the need for “appropriate referral for optimized multidisciplinary care for patients with autoimmune rheumatic diseases during the recovery period following COVID-19,” added Dr. Nune, who works for Southport (England) and Ormskirk Hospital NHS Trust.

In an interview, he noted that it was patients who had a severe COVID-19 course or had other coexisting conditions that appeared to experience more long-term effects than did their less-affected counterparts.

Commenting on the study, Jeffrey A. Sparks, MD, MMSc, told this news organization: “This is one of the first studies to find that the prevalence of long COVID is higher among people with systemic rheumatic diseases than those without.”

Dr. Sparks, who is based at Brigham and Women’s Hospital and Harvard Medical School in Boston, added: “Since the symptoms of long COVID and rheumatic diseases can overlap substantially, more work will need to be done to determine whether COVID may have induced flares, new symptoms, or whether the finding is due to the presence of the chronic rheumatic disease.”
 

The COVAD study

Using an electronic survey platform, the COVAD study has been set up to look at the long-term efficacy and safety of COVID-19 vaccinations in patients with AIRDs. It’s now a large international effort involving more than 150 collaborating clinics in 106 countries.

A huge amount of data has been collected. “We collected demographics, details of autoimmune disease, including treatment, comorbidity, COVID infection, vaccination history and outcomes, date on flares, and validated patient-reported outcomes, including pain, fatigue, physical function, and quality of life,” Dr. Nune said in his presentation.

A total of 12,358 people who were invited to participate responded to the e-survey. Of them, 2,640 were confirmed to have COVID-19. Because the analysis aimed to look at PCC, anyone who had completed the survey less than 3 months after infection was excluded. This left 1,677 eligible respondents, of whom, an overall 8.7% (n = 136) were identified as having PCC.

“The [WHO] definition for PCC was employed, which is persistent signs or symptoms beyond 3 months of COVID-19 infection lasting at least 2 months,” Dr. Nune told this news organization.

“Symptoms could be anything from fatigue to breathlessness to arthralgias,” he added. However, the focus of the present analysis was to look at how many people were experiencing the condition rather than specific symptoms.

A higher risk for PCC was seen in women than in men (OR, 2.9; 95% CI, 1.1-7.7; P = .037) in the entire cohort.

In addition, those with comorbidities were found to have a greater chance of long-term sequelae from COVID-19 than were those without comorbid disease (OR, 2.8; 95% CI, 1.4-5.7; P = .005).

Patients who experienced more severe acute COVID-19, such as those who needed intensive care treatment, oxygen therapy, or advanced treatment for COVID-19 with monoclonal antibodies, were significantly more likely to later have PCC than were those who did not (OR, 3.8; 95% CI, 1.1-13.6; P = .039).

Having PCC was also associated with poorer patient-reported outcomes for physical function, compared with not having PCC. “However, no association with disease flares of underlying rheumatic diseases or immunosuppressive drugs used were noted,” Dr. Nune said.

These new findings from the COVAD study should be published soon. Dr. Nune suggested that the findings might be used to help identify patients early so that they can be referred to the appropriate services in good time.

The COVAD study was independently supported. Dr. Nune reports no relevant financial relationships. Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care. Dr. Sparks has received research support from Bristol-Myers Squibb and performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer.
 

MANCHESTER, England – Data from the COVAD-2 e-survey suggest that people with a rheumatic disease are twice as likely as are those without to experience long-term effects after contracting COVID-19.

The prevalence of post–COVID-19 condition (PCC), the term the World Health Organization advocates for describing the widely popularized term long COVID, was 10.8% among people with autoimmune rheumatic diseases (AIRDs) vs. 5.3% among those with no autoimmune condition (designated as “healthy controls”). The odds ratio was 2.1, with a 95% confidence interval of 1.4-3.2 and a P-value of .002.

The prevalence in people with nonrheumatic autoimmune diseases was also higher than it was in the control participants but still lower, at 7.3%, than in those with AIRDs.

Sara Freeman/MDedge News

“Our findings highlight the importance of close monitoring for PCC,” Arvind Nune, MBBCh, MSc, said in a virtual poster presentation at the annual meeting of the British Society for Rheumatology.

They also show the need for “appropriate referral for optimized multidisciplinary care for patients with autoimmune rheumatic diseases during the recovery period following COVID-19,” added Dr. Nune, who works for Southport (England) and Ormskirk Hospital NHS Trust.

In an interview, he noted that it was patients who had a severe COVID-19 course or had other coexisting conditions that appeared to experience more long-term effects than did their less-affected counterparts.

Commenting on the study, Jeffrey A. Sparks, MD, MMSc, told this news organization: “This is one of the first studies to find that the prevalence of long COVID is higher among people with systemic rheumatic diseases than those without.”

Dr. Sparks, who is based at Brigham and Women’s Hospital and Harvard Medical School in Boston, added: “Since the symptoms of long COVID and rheumatic diseases can overlap substantially, more work will need to be done to determine whether COVID may have induced flares, new symptoms, or whether the finding is due to the presence of the chronic rheumatic disease.”
 

The COVAD study

Using an electronic survey platform, the COVAD study has been set up to look at the long-term efficacy and safety of COVID-19 vaccinations in patients with AIRDs. It’s now a large international effort involving more than 150 collaborating clinics in 106 countries.

A huge amount of data has been collected. “We collected demographics, details of autoimmune disease, including treatment, comorbidity, COVID infection, vaccination history and outcomes, date on flares, and validated patient-reported outcomes, including pain, fatigue, physical function, and quality of life,” Dr. Nune said in his presentation.

A total of 12,358 people who were invited to participate responded to the e-survey. Of them, 2,640 were confirmed to have COVID-19. Because the analysis aimed to look at PCC, anyone who had completed the survey less than 3 months after infection was excluded. This left 1,677 eligible respondents, of whom, an overall 8.7% (n = 136) were identified as having PCC.

“The [WHO] definition for PCC was employed, which is persistent signs or symptoms beyond 3 months of COVID-19 infection lasting at least 2 months,” Dr. Nune told this news organization.

“Symptoms could be anything from fatigue to breathlessness to arthralgias,” he added. However, the focus of the present analysis was to look at how many people were experiencing the condition rather than specific symptoms.

A higher risk for PCC was seen in women than in men (OR, 2.9; 95% CI, 1.1-7.7; P = .037) in the entire cohort.

In addition, those with comorbidities were found to have a greater chance of long-term sequelae from COVID-19 than were those without comorbid disease (OR, 2.8; 95% CI, 1.4-5.7; P = .005).

Patients who experienced more severe acute COVID-19, such as those who needed intensive care treatment, oxygen therapy, or advanced treatment for COVID-19 with monoclonal antibodies, were significantly more likely to later have PCC than were those who did not (OR, 3.8; 95% CI, 1.1-13.6; P = .039).

Having PCC was also associated with poorer patient-reported outcomes for physical function, compared with not having PCC. “However, no association with disease flares of underlying rheumatic diseases or immunosuppressive drugs used were noted,” Dr. Nune said.

These new findings from the COVAD study should be published soon. Dr. Nune suggested that the findings might be used to help identify patients early so that they can be referred to the appropriate services in good time.

The COVAD study was independently supported. Dr. Nune reports no relevant financial relationships. Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care. Dr. Sparks has received research support from Bristol-Myers Squibb and performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer.
 

MANCHESTER, England – Data from the COVAD-2 e-survey suggest that people with a rheumatic disease are twice as likely as are those without to experience long-term effects after contracting COVID-19.

The prevalence of post–COVID-19 condition (PCC), the term the World Health Organization advocates for describing the widely popularized term long COVID, was 10.8% among people with autoimmune rheumatic diseases (AIRDs) vs. 5.3% among those with no autoimmune condition (designated as “healthy controls”). The odds ratio was 2.1, with a 95% confidence interval of 1.4-3.2 and a P-value of .002.

The prevalence in people with nonrheumatic autoimmune diseases was also higher than it was in the control participants but still lower, at 7.3%, than in those with AIRDs.

Sara Freeman/MDedge News

“Our findings highlight the importance of close monitoring for PCC,” Arvind Nune, MBBCh, MSc, said in a virtual poster presentation at the annual meeting of the British Society for Rheumatology.

They also show the need for “appropriate referral for optimized multidisciplinary care for patients with autoimmune rheumatic diseases during the recovery period following COVID-19,” added Dr. Nune, who works for Southport (England) and Ormskirk Hospital NHS Trust.

In an interview, he noted that it was patients who had a severe COVID-19 course or had other coexisting conditions that appeared to experience more long-term effects than did their less-affected counterparts.

Commenting on the study, Jeffrey A. Sparks, MD, MMSc, told this news organization: “This is one of the first studies to find that the prevalence of long COVID is higher among people with systemic rheumatic diseases than those without.”

Dr. Sparks, who is based at Brigham and Women’s Hospital and Harvard Medical School in Boston, added: “Since the symptoms of long COVID and rheumatic diseases can overlap substantially, more work will need to be done to determine whether COVID may have induced flares, new symptoms, or whether the finding is due to the presence of the chronic rheumatic disease.”
 

The COVAD study

Using an electronic survey platform, the COVAD study has been set up to look at the long-term efficacy and safety of COVID-19 vaccinations in patients with AIRDs. It’s now a large international effort involving more than 150 collaborating clinics in 106 countries.

A huge amount of data has been collected. “We collected demographics, details of autoimmune disease, including treatment, comorbidity, COVID infection, vaccination history and outcomes, date on flares, and validated patient-reported outcomes, including pain, fatigue, physical function, and quality of life,” Dr. Nune said in his presentation.

A total of 12,358 people who were invited to participate responded to the e-survey. Of them, 2,640 were confirmed to have COVID-19. Because the analysis aimed to look at PCC, anyone who had completed the survey less than 3 months after infection was excluded. This left 1,677 eligible respondents, of whom, an overall 8.7% (n = 136) were identified as having PCC.

“The [WHO] definition for PCC was employed, which is persistent signs or symptoms beyond 3 months of COVID-19 infection lasting at least 2 months,” Dr. Nune told this news organization.

“Symptoms could be anything from fatigue to breathlessness to arthralgias,” he added. However, the focus of the present analysis was to look at how many people were experiencing the condition rather than specific symptoms.

A higher risk for PCC was seen in women than in men (OR, 2.9; 95% CI, 1.1-7.7; P = .037) in the entire cohort.

In addition, those with comorbidities were found to have a greater chance of long-term sequelae from COVID-19 than were those without comorbid disease (OR, 2.8; 95% CI, 1.4-5.7; P = .005).

Patients who experienced more severe acute COVID-19, such as those who needed intensive care treatment, oxygen therapy, or advanced treatment for COVID-19 with monoclonal antibodies, were significantly more likely to later have PCC than were those who did not (OR, 3.8; 95% CI, 1.1-13.6; P = .039).

Having PCC was also associated with poorer patient-reported outcomes for physical function, compared with not having PCC. “However, no association with disease flares of underlying rheumatic diseases or immunosuppressive drugs used were noted,” Dr. Nune said.

These new findings from the COVAD study should be published soon. Dr. Nune suggested that the findings might be used to help identify patients early so that they can be referred to the appropriate services in good time.

The COVAD study was independently supported. Dr. Nune reports no relevant financial relationships. Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care. Dr. Sparks has received research support from Bristol-Myers Squibb and performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer.
 

Joint hypermobility syndrome, popularly known as being double-jointed, may be a common but underrecognized disorder in adults that is difficult to diagnose and often mistaken for fibromyalgia or other conditions.

So said Matthew B. Carroll, MD, a board-certified rheumatologist with Singing River Health System, Ocean Springs, Miss., during a presentation about hypermobility at the annual meeting of the American College of Physicians.

According to Dr. Carroll, the concept of a hypermobility spectrum disorder (HSD) associated with double-jointedness is relatively new and not part of the conventional nomenclature.

“One of the frustrations about HSD is that there really aren’t any good theories,” as to why some with hypermobility suffer from the syndrome while others do not, Dr. Carroll said.

Hypermobility is defined as having joints that are looser than normal. Examples of this include hyperextending the forearm at the elbow or pressing the thumb against the surface of the forearm.

Approximately 20% of the adult population has hypermobility, which affects women more than men and is more common in younger people. In children ages 3-19 years, 32% of girls and 18% of boys are hypermobile.

But the condition is not a diagnosis, “it’s a descriptor of a finding that you notice on a physical exam,” Dr. Carroll said.
 

When flexibility is a problem

Although hypermobility often is benign and rarely progresses to more serious health issues, HSD can cause symptoms such as recurrent dislocations, joint pain, and other degenerative changes. Recent evidence suggests that abnormal bleeding may also accompany hypermobility.

A 2013 survey in the United Kingdom found that about 3% of respondents reported pain as a consequence of their hypermobility. Dr. Carroll hypothesized that up to a quarter of those diagnosed with hypermobility have some associated pain.

“We kind of think of hypermobility as either being benign, or you kind of have it as a kid and grow out of it,” Dr. Carroll said. “But the reality is a lot of our patients keep that into adulthood and can have problems as a consequence.”

Because some of the symptoms of HSD, such as abdominal pain and fatigue, mimic other whole-body pain conditions, specifically fibromyalgia, Dr. Carroll said it likely is widely undiagnosed.

“I think a lot of these patients were diagnosed with fibromyalgia,” Dr. Carroll said. “It’s incumbent upon us to be able to start teasing some of those nuances out, or at least have rheumatology help you and other specialists figure out where you can go with these patients and their health.”
 

Causes of HSD

HSD can be both genetic and environmental in nature; sports injuries, spontaneous dislocations, and a fear of injury leading to a sedentary lifestyle should also be considered. The condition can overlap with Ehlers-Danlos syndromes, a rare group of inherited conditions that affect connectivity tissue.

Treating patients with HSD requires a multidisciplinary approach, including primary care, rheumatologists, geneticists, and orthopedists. If primary care physicians suspect their patient has hypermobility, they should explore this possibility before moving on to another diagnosis. Whether an adult has or had joint mobility can be determined through a series of simple questions:

• Can you bend your thumb to touch your forearm?
• As a child, did you amuse your friends by contorting your body into strange shapes?
• Do you consider yourself double-jointed?

“It gets really kind of muddy and really difficult to tease out, but I think it’s something that takes time in an iterative process to figure out,” Dr. Carroll said.

Treatment options for HSD are limited. No disease-directed pharmacologic agents exist, and interventions in general lack rigorous studies to support their use. Dr. Carroll recommends anti-inflammatory drugs and physical therapy as first-line approaches. He also stressed that lifestyle interventions – particularly exercise and weight loss – are essential. The role of surgery at this time is unclear and only used in highly selected cases. An appointment with a geneticist could also be necessary to explore family history and look for Ehlers‐Danlos syndromes. 

“You’re going to need several different specialists to try to really help our patients get back up and running,” he said.

Dr. Carroll reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Joint hypermobility syndrome, popularly known as being double-jointed, may be a common but underrecognized disorder in adults that is difficult to diagnose and often mistaken for fibromyalgia or other conditions.

So said Matthew B. Carroll, MD, a board-certified rheumatologist with Singing River Health System, Ocean Springs, Miss., during a presentation about hypermobility at the annual meeting of the American College of Physicians.

According to Dr. Carroll, the concept of a hypermobility spectrum disorder (HSD) associated with double-jointedness is relatively new and not part of the conventional nomenclature.

“One of the frustrations about HSD is that there really aren’t any good theories,” as to why some with hypermobility suffer from the syndrome while others do not, Dr. Carroll said.

Hypermobility is defined as having joints that are looser than normal. Examples of this include hyperextending the forearm at the elbow or pressing the thumb against the surface of the forearm.

Approximately 20% of the adult population has hypermobility, which affects women more than men and is more common in younger people. In children ages 3-19 years, 32% of girls and 18% of boys are hypermobile.

But the condition is not a diagnosis, “it’s a descriptor of a finding that you notice on a physical exam,” Dr. Carroll said.
 

When flexibility is a problem

Although hypermobility often is benign and rarely progresses to more serious health issues, HSD can cause symptoms such as recurrent dislocations, joint pain, and other degenerative changes. Recent evidence suggests that abnormal bleeding may also accompany hypermobility.

A 2013 survey in the United Kingdom found that about 3% of respondents reported pain as a consequence of their hypermobility. Dr. Carroll hypothesized that up to a quarter of those diagnosed with hypermobility have some associated pain.

“We kind of think of hypermobility as either being benign, or you kind of have it as a kid and grow out of it,” Dr. Carroll said. “But the reality is a lot of our patients keep that into adulthood and can have problems as a consequence.”

Because some of the symptoms of HSD, such as abdominal pain and fatigue, mimic other whole-body pain conditions, specifically fibromyalgia, Dr. Carroll said it likely is widely undiagnosed.

“I think a lot of these patients were diagnosed with fibromyalgia,” Dr. Carroll said. “It’s incumbent upon us to be able to start teasing some of those nuances out, or at least have rheumatology help you and other specialists figure out where you can go with these patients and their health.”
 

Causes of HSD

HSD can be both genetic and environmental in nature; sports injuries, spontaneous dislocations, and a fear of injury leading to a sedentary lifestyle should also be considered. The condition can overlap with Ehlers-Danlos syndromes, a rare group of inherited conditions that affect connectivity tissue.

Treating patients with HSD requires a multidisciplinary approach, including primary care, rheumatologists, geneticists, and orthopedists. If primary care physicians suspect their patient has hypermobility, they should explore this possibility before moving on to another diagnosis. Whether an adult has or had joint mobility can be determined through a series of simple questions:

• Can you bend your thumb to touch your forearm?
• As a child, did you amuse your friends by contorting your body into strange shapes?
• Do you consider yourself double-jointed?

“It gets really kind of muddy and really difficult to tease out, but I think it’s something that takes time in an iterative process to figure out,” Dr. Carroll said.

Treatment options for HSD are limited. No disease-directed pharmacologic agents exist, and interventions in general lack rigorous studies to support their use. Dr. Carroll recommends anti-inflammatory drugs and physical therapy as first-line approaches. He also stressed that lifestyle interventions – particularly exercise and weight loss – are essential. The role of surgery at this time is unclear and only used in highly selected cases. An appointment with a geneticist could also be necessary to explore family history and look for Ehlers‐Danlos syndromes. 

“You’re going to need several different specialists to try to really help our patients get back up and running,” he said.

Dr. Carroll reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Joint hypermobility syndrome, popularly known as being double-jointed, may be a common but underrecognized disorder in adults that is difficult to diagnose and often mistaken for fibromyalgia or other conditions.

So said Matthew B. Carroll, MD, a board-certified rheumatologist with Singing River Health System, Ocean Springs, Miss., during a presentation about hypermobility at the annual meeting of the American College of Physicians.

According to Dr. Carroll, the concept of a hypermobility spectrum disorder (HSD) associated with double-jointedness is relatively new and not part of the conventional nomenclature.

“One of the frustrations about HSD is that there really aren’t any good theories,” as to why some with hypermobility suffer from the syndrome while others do not, Dr. Carroll said.

Hypermobility is defined as having joints that are looser than normal. Examples of this include hyperextending the forearm at the elbow or pressing the thumb against the surface of the forearm.

Approximately 20% of the adult population has hypermobility, which affects women more than men and is more common in younger people. In children ages 3-19 years, 32% of girls and 18% of boys are hypermobile.

But the condition is not a diagnosis, “it’s a descriptor of a finding that you notice on a physical exam,” Dr. Carroll said.
 

When flexibility is a problem

Although hypermobility often is benign and rarely progresses to more serious health issues, HSD can cause symptoms such as recurrent dislocations, joint pain, and other degenerative changes. Recent evidence suggests that abnormal bleeding may also accompany hypermobility.

A 2013 survey in the United Kingdom found that about 3% of respondents reported pain as a consequence of their hypermobility. Dr. Carroll hypothesized that up to a quarter of those diagnosed with hypermobility have some associated pain.

“We kind of think of hypermobility as either being benign, or you kind of have it as a kid and grow out of it,” Dr. Carroll said. “But the reality is a lot of our patients keep that into adulthood and can have problems as a consequence.”

Because some of the symptoms of HSD, such as abdominal pain and fatigue, mimic other whole-body pain conditions, specifically fibromyalgia, Dr. Carroll said it likely is widely undiagnosed.

“I think a lot of these patients were diagnosed with fibromyalgia,” Dr. Carroll said. “It’s incumbent upon us to be able to start teasing some of those nuances out, or at least have rheumatology help you and other specialists figure out where you can go with these patients and their health.”
 

Causes of HSD

HSD can be both genetic and environmental in nature; sports injuries, spontaneous dislocations, and a fear of injury leading to a sedentary lifestyle should also be considered. The condition can overlap with Ehlers-Danlos syndromes, a rare group of inherited conditions that affect connectivity tissue.

Treating patients with HSD requires a multidisciplinary approach, including primary care, rheumatologists, geneticists, and orthopedists. If primary care physicians suspect their patient has hypermobility, they should explore this possibility before moving on to another diagnosis. Whether an adult has or had joint mobility can be determined through a series of simple questions:

• Can you bend your thumb to touch your forearm?
• As a child, did you amuse your friends by contorting your body into strange shapes?
• Do you consider yourself double-jointed?

“It gets really kind of muddy and really difficult to tease out, but I think it’s something that takes time in an iterative process to figure out,” Dr. Carroll said.

Treatment options for HSD are limited. No disease-directed pharmacologic agents exist, and interventions in general lack rigorous studies to support their use. Dr. Carroll recommends anti-inflammatory drugs and physical therapy as first-line approaches. He also stressed that lifestyle interventions – particularly exercise and weight loss – are essential. The role of surgery at this time is unclear and only used in highly selected cases. An appointment with a geneticist could also be necessary to explore family history and look for Ehlers‐Danlos syndromes. 

“You’re going to need several different specialists to try to really help our patients get back up and running,” he said.

Dr. Carroll reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

MANCHESTER, ENGLAND – The use of NSAIDs may mask the true level of inflammation of the sacroiliac joint (SIJ), as seen on MRI, among people with axial spondyloarthritis (axSpA), according to results of the DyNAMISM study.

“We’ve found that in about one in four patients, NSAIDs make a difference to the scan results,” Gareth T. Jones, PhD, said at the annual meeting of the British Society for Rheumatology.

Sara Freeman/MDedge News

A total of 23% of patients whose MRI results were positive for sacroiliitis when no NSAIDs had been used for a couple of weeks received negative MRI results 6 weeks after the NSAIDs were reinstated.

“This is important in terms of diagnosis, in terms of disease classification, and may be important in terms of future treatment decisions,” added Dr. Jones, professor of epidemiology at the Aberdeen Centre for Arthritis and Musculoskeletal Health at the University of Aberdeen, (Scotland).

“Our recommendation from these results is that if a patient is willing to attempt to wash out [NSAIDs] prior to an MRI, we would recommend that they do so,” Dr. Jones said.
 

NSAIDs and AxSpA inflammation

“NSAIDs are often used as the first-line treatment for axial spondyloarthritis due to their ability to effectively reduce pain and stiffness associated with the condition,” Denis Poddubnyy, MD, who was not involved in the research, told this news organization.

“However, there is still a question as to whether NSAIDs have a true anti-inflammatory effect on the axial inflammation, as detected by MRI,” added Dr. Poddubnyy, head of rheumatology at Charité–Universitätsmedizin Berlin in Germany.

With an absence of randomized, controlled trials, it remains “uncertain how much of the observed reduction in inflammation is attributable to the natural course of the disease and spontaneous resolution of inflammation rather than the effect of NSAIDs,” Dr. Poddubnyy said.
 

The DyNAMISM Study

“Sacroiliitis is a painful inflammatory condition. This is investigated looking for the evidence of inflammation on MRI, but many patients are taking anti-inflammatory medication,” Dr. Jones said at the meeting.

“So perhaps patients are taking drugs [that are] hiding the very thing that we’re looking for,” he added. Hence, the DyNAMISM study (Do Nonsteroidal Anti-inflammatory Drugs Mask Inflammation in Spondyloarthritis on MRI) was conceived.

The researchers recruited 311 adults with suspected or established axSpA who were taking daily NSAIDs such as ibuprofen or diclofenac across 34 centers in England and Scotland. Patients taking other anti-inflammatory medications that could not be stopped were excluded, as were patients who were currently taking or had recently taken tumor necrosis factor inhibitors.

The study used a standardized MRI protocol. Two independent readers experienced in scoring SIJ scans were employed; a third was used when the two disagreed. The primary outcome was meeting the Assessment of Spondyloarthritis international Society criteria for a positive result on MRI.

The average age of the study subjects was 42 years, 62% were men, and 87% were White. The median duration of symptoms was 9 years, and the median time since diagnosis was 1 year.

The study design required that patients stop NSAID use over a period of 1-2 weeks before undergoing an MRI scan, which 286 did. Of these, 146 received MRI results that were positive for SIJ inflammation; those patients continued in the study. The 140 patients with negative scans were excluded. Patients could then resume taking NSAIDs before being scanned again around 6 weeks later. In all, 129 patients underwent both MRI scans.
 

How much might fluctuating inflammation matter?

‘It’s a shame you didn’t scan the negative people, because the natural history is a fluctuating inflammation,” Fraser Birrell, MBChB, PhD, of Newcastle University, Newcastle upon Tyne, England, pointed out in discussion.

“Nonsteroidals are modestly effective and probably made no difference,” he argued. “I would have expected a certain proportion of the negatives are positive.”

The study had a pragmatic design, Dr. Jones countered. “We had enormous debate before the study; it would have been nice to do a sort of a randomized, crossover design, but it would have resulted in a lot of inefficiency.”

Regarding the duration of the NSAID washout period, Dr. Jones noted that they saw little difference between shorter or longer washout periods and that the data showed that “a 2-week washout is a reasonable target.”

Performing the second scan 6 weeks after NSAIDs were reinstated “exceeds the period where clinical benefits should be expected. It may be that if we’d waited longer, the proportion would have gone up. So, we would argue that actually, if anything, that 23% may be an underestimate of the real effect.”

Although some patients may have declined to participate in the study because they did not want to stop taking NSAIDs, Dr. Jones noted that a good proportion did stop taking them, and so the study shows that patients can tolerate washout. Around 45% of patients reported experiencing disease flares during this time, but this did not have any significant effect on validated disease activity or pain measures, Dr. Jones reported.

So, if patients are willing to stop NSAIDs before a scan, “they should be counseled that they may experience a small increase in disease activity and spinal pain, but also to be counseled that the majority of patients can tolerate this,” Dr. Jones suggested.

Trials are needed, Dr. Poddubnyy said: “Future randomized, controlled studies are needed to conclusively determine the efficacy of NSAIDs in reducing inflammation in the axial skeleton of axSpA patients.”

Dr. Poddubnyy added: “It would also be valuable to assess in a randomized setting whether the use of NSAIDs impacts the diagnostic performance of MRI, which takes into account not only inflammatory but also structural changes, which are not influenced by NSAIDs.”

The DyNAMISM study was funded by Arthritis Research UK and was run by the University of Aberdeen in conjunction with NHS Grampian, Scotland. Dr. Jones has disclosed no relevant financial relationships. Dr. Poddubnyy disclosed ties with AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Medscape, Merck Sharp & Dohme, Moonlake, Novartis, PeerVoice, Pfizer, Samsung Bioepis, and UCB.

A version of this article originally appeared on Medscape.com.

MANCHESTER, ENGLAND – The use of NSAIDs may mask the true level of inflammation of the sacroiliac joint (SIJ), as seen on MRI, among people with axial spondyloarthritis (axSpA), according to results of the DyNAMISM study.

“We’ve found that in about one in four patients, NSAIDs make a difference to the scan results,” Gareth T. Jones, PhD, said at the annual meeting of the British Society for Rheumatology.

Sara Freeman/MDedge News

A total of 23% of patients whose MRI results were positive for sacroiliitis when no NSAIDs had been used for a couple of weeks received negative MRI results 6 weeks after the NSAIDs were reinstated.

“This is important in terms of diagnosis, in terms of disease classification, and may be important in terms of future treatment decisions,” added Dr. Jones, professor of epidemiology at the Aberdeen Centre for Arthritis and Musculoskeletal Health at the University of Aberdeen, (Scotland).

“Our recommendation from these results is that if a patient is willing to attempt to wash out [NSAIDs] prior to an MRI, we would recommend that they do so,” Dr. Jones said.
 

NSAIDs and AxSpA inflammation

“NSAIDs are often used as the first-line treatment for axial spondyloarthritis due to their ability to effectively reduce pain and stiffness associated with the condition,” Denis Poddubnyy, MD, who was not involved in the research, told this news organization.

“However, there is still a question as to whether NSAIDs have a true anti-inflammatory effect on the axial inflammation, as detected by MRI,” added Dr. Poddubnyy, head of rheumatology at Charité–Universitätsmedizin Berlin in Germany.

With an absence of randomized, controlled trials, it remains “uncertain how much of the observed reduction in inflammation is attributable to the natural course of the disease and spontaneous resolution of inflammation rather than the effect of NSAIDs,” Dr. Poddubnyy said.
 

The DyNAMISM Study

“Sacroiliitis is a painful inflammatory condition. This is investigated looking for the evidence of inflammation on MRI, but many patients are taking anti-inflammatory medication,” Dr. Jones said at the meeting.

“So perhaps patients are taking drugs [that are] hiding the very thing that we’re looking for,” he added. Hence, the DyNAMISM study (Do Nonsteroidal Anti-inflammatory Drugs Mask Inflammation in Spondyloarthritis on MRI) was conceived.

The researchers recruited 311 adults with suspected or established axSpA who were taking daily NSAIDs such as ibuprofen or diclofenac across 34 centers in England and Scotland. Patients taking other anti-inflammatory medications that could not be stopped were excluded, as were patients who were currently taking or had recently taken tumor necrosis factor inhibitors.

The study used a standardized MRI protocol. Two independent readers experienced in scoring SIJ scans were employed; a third was used when the two disagreed. The primary outcome was meeting the Assessment of Spondyloarthritis international Society criteria for a positive result on MRI.

The average age of the study subjects was 42 years, 62% were men, and 87% were White. The median duration of symptoms was 9 years, and the median time since diagnosis was 1 year.

The study design required that patients stop NSAID use over a period of 1-2 weeks before undergoing an MRI scan, which 286 did. Of these, 146 received MRI results that were positive for SIJ inflammation; those patients continued in the study. The 140 patients with negative scans were excluded. Patients could then resume taking NSAIDs before being scanned again around 6 weeks later. In all, 129 patients underwent both MRI scans.
 

How much might fluctuating inflammation matter?

‘It’s a shame you didn’t scan the negative people, because the natural history is a fluctuating inflammation,” Fraser Birrell, MBChB, PhD, of Newcastle University, Newcastle upon Tyne, England, pointed out in discussion.

“Nonsteroidals are modestly effective and probably made no difference,” he argued. “I would have expected a certain proportion of the negatives are positive.”

The study had a pragmatic design, Dr. Jones countered. “We had enormous debate before the study; it would have been nice to do a sort of a randomized, crossover design, but it would have resulted in a lot of inefficiency.”

Regarding the duration of the NSAID washout period, Dr. Jones noted that they saw little difference between shorter or longer washout periods and that the data showed that “a 2-week washout is a reasonable target.”

Performing the second scan 6 weeks after NSAIDs were reinstated “exceeds the period where clinical benefits should be expected. It may be that if we’d waited longer, the proportion would have gone up. So, we would argue that actually, if anything, that 23% may be an underestimate of the real effect.”

Although some patients may have declined to participate in the study because they did not want to stop taking NSAIDs, Dr. Jones noted that a good proportion did stop taking them, and so the study shows that patients can tolerate washout. Around 45% of patients reported experiencing disease flares during this time, but this did not have any significant effect on validated disease activity or pain measures, Dr. Jones reported.

So, if patients are willing to stop NSAIDs before a scan, “they should be counseled that they may experience a small increase in disease activity and spinal pain, but also to be counseled that the majority of patients can tolerate this,” Dr. Jones suggested.

Trials are needed, Dr. Poddubnyy said: “Future randomized, controlled studies are needed to conclusively determine the efficacy of NSAIDs in reducing inflammation in the axial skeleton of axSpA patients.”

Dr. Poddubnyy added: “It would also be valuable to assess in a randomized setting whether the use of NSAIDs impacts the diagnostic performance of MRI, which takes into account not only inflammatory but also structural changes, which are not influenced by NSAIDs.”

The DyNAMISM study was funded by Arthritis Research UK and was run by the University of Aberdeen in conjunction with NHS Grampian, Scotland. Dr. Jones has disclosed no relevant financial relationships. Dr. Poddubnyy disclosed ties with AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Medscape, Merck Sharp & Dohme, Moonlake, Novartis, PeerVoice, Pfizer, Samsung Bioepis, and UCB.

A version of this article originally appeared on Medscape.com.

MANCHESTER, ENGLAND – The use of NSAIDs may mask the true level of inflammation of the sacroiliac joint (SIJ), as seen on MRI, among people with axial spondyloarthritis (axSpA), according to results of the DyNAMISM study.

“We’ve found that in about one in four patients, NSAIDs make a difference to the scan results,” Gareth T. Jones, PhD, said at the annual meeting of the British Society for Rheumatology.

Sara Freeman/MDedge News

A total of 23% of patients whose MRI results were positive for sacroiliitis when no NSAIDs had been used for a couple of weeks received negative MRI results 6 weeks after the NSAIDs were reinstated.

“This is important in terms of diagnosis, in terms of disease classification, and may be important in terms of future treatment decisions,” added Dr. Jones, professor of epidemiology at the Aberdeen Centre for Arthritis and Musculoskeletal Health at the University of Aberdeen, (Scotland).

“Our recommendation from these results is that if a patient is willing to attempt to wash out [NSAIDs] prior to an MRI, we would recommend that they do so,” Dr. Jones said.
 

NSAIDs and AxSpA inflammation

“NSAIDs are often used as the first-line treatment for axial spondyloarthritis due to their ability to effectively reduce pain and stiffness associated with the condition,” Denis Poddubnyy, MD, who was not involved in the research, told this news organization.

“However, there is still a question as to whether NSAIDs have a true anti-inflammatory effect on the axial inflammation, as detected by MRI,” added Dr. Poddubnyy, head of rheumatology at Charité–Universitätsmedizin Berlin in Germany.

With an absence of randomized, controlled trials, it remains “uncertain how much of the observed reduction in inflammation is attributable to the natural course of the disease and spontaneous resolution of inflammation rather than the effect of NSAIDs,” Dr. Poddubnyy said.
 

The DyNAMISM Study

“Sacroiliitis is a painful inflammatory condition. This is investigated looking for the evidence of inflammation on MRI, but many patients are taking anti-inflammatory medication,” Dr. Jones said at the meeting.

“So perhaps patients are taking drugs [that are] hiding the very thing that we’re looking for,” he added. Hence, the DyNAMISM study (Do Nonsteroidal Anti-inflammatory Drugs Mask Inflammation in Spondyloarthritis on MRI) was conceived.

The researchers recruited 311 adults with suspected or established axSpA who were taking daily NSAIDs such as ibuprofen or diclofenac across 34 centers in England and Scotland. Patients taking other anti-inflammatory medications that could not be stopped were excluded, as were patients who were currently taking or had recently taken tumor necrosis factor inhibitors.

The study used a standardized MRI protocol. Two independent readers experienced in scoring SIJ scans were employed; a third was used when the two disagreed. The primary outcome was meeting the Assessment of Spondyloarthritis international Society criteria for a positive result on MRI.

The average age of the study subjects was 42 years, 62% were men, and 87% were White. The median duration of symptoms was 9 years, and the median time since diagnosis was 1 year.

The study design required that patients stop NSAID use over a period of 1-2 weeks before undergoing an MRI scan, which 286 did. Of these, 146 received MRI results that were positive for SIJ inflammation; those patients continued in the study. The 140 patients with negative scans were excluded. Patients could then resume taking NSAIDs before being scanned again around 6 weeks later. In all, 129 patients underwent both MRI scans.
 

How much might fluctuating inflammation matter?

‘It’s a shame you didn’t scan the negative people, because the natural history is a fluctuating inflammation,” Fraser Birrell, MBChB, PhD, of Newcastle University, Newcastle upon Tyne, England, pointed out in discussion.

“Nonsteroidals are modestly effective and probably made no difference,” he argued. “I would have expected a certain proportion of the negatives are positive.”

The study had a pragmatic design, Dr. Jones countered. “We had enormous debate before the study; it would have been nice to do a sort of a randomized, crossover design, but it would have resulted in a lot of inefficiency.”

Regarding the duration of the NSAID washout period, Dr. Jones noted that they saw little difference between shorter or longer washout periods and that the data showed that “a 2-week washout is a reasonable target.”

Performing the second scan 6 weeks after NSAIDs were reinstated “exceeds the period where clinical benefits should be expected. It may be that if we’d waited longer, the proportion would have gone up. So, we would argue that actually, if anything, that 23% may be an underestimate of the real effect.”

Although some patients may have declined to participate in the study because they did not want to stop taking NSAIDs, Dr. Jones noted that a good proportion did stop taking them, and so the study shows that patients can tolerate washout. Around 45% of patients reported experiencing disease flares during this time, but this did not have any significant effect on validated disease activity or pain measures, Dr. Jones reported.

So, if patients are willing to stop NSAIDs before a scan, “they should be counseled that they may experience a small increase in disease activity and spinal pain, but also to be counseled that the majority of patients can tolerate this,” Dr. Jones suggested.

Trials are needed, Dr. Poddubnyy said: “Future randomized, controlled studies are needed to conclusively determine the efficacy of NSAIDs in reducing inflammation in the axial skeleton of axSpA patients.”

Dr. Poddubnyy added: “It would also be valuable to assess in a randomized setting whether the use of NSAIDs impacts the diagnostic performance of MRI, which takes into account not only inflammatory but also structural changes, which are not influenced by NSAIDs.”

The DyNAMISM study was funded by Arthritis Research UK and was run by the University of Aberdeen in conjunction with NHS Grampian, Scotland. Dr. Jones has disclosed no relevant financial relationships. Dr. Poddubnyy disclosed ties with AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Medscape, Merck Sharp & Dohme, Moonlake, Novartis, PeerVoice, Pfizer, Samsung Bioepis, and UCB.

A version of this article originally appeared on Medscape.com.

MANCHESTER, ENGLAND – Janus kinase (JAK) inhibitors may be associated with a higher risk for cancer relative to tumor necrosis factor (TNF) inhibitors, according to a meta-analysis reported at the annual meeting of the British Society for Rheumatology.

Looking at all phase 2, 3, and 4 trials and long-term extension studies across the indications of rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, and atopic dermatitis, the risk ratio for any cancer developing was 1.63 when compared with anti-TNF therapy (95% confidence interval, 1.27-2.09).

Sara Freeman/MDedge News

By comparison, JAK inhibitor use was not significantly associated with any greater risk for cancer than methotrexate (RR, 1.06; 95% confidence interval, 0.58-1.94) or placebo (RR, 1.16; 95% CI, 0.75-1.80).

“Our data suggests that rather than JAK inhibitors necessarily being harmful, it could be more a case of TNF inhibitors being protective,” said Christopher Stovin, MBChB, a specialist registrar in rheumatology at the Princess Royal University Hospital, King’s College Hospital NHS Trust, London.

“We should stress that these are rare events in our study, roughly around 1 in every 100 patient-years of exposure,” Dr. Stovin said.

“Despite having over 80,000 years of patient exposure, the median follow-up duration for JAK inhibitors was still only 118 weeks, which for cancers [that] obviously have long latency periods is still a relatively small duration of time,” the researcher added.

“People worry about the drugs. But there is a possibility that [a] disturbed immune system plays a role per se in development of cancers,” consultant rheumatologist Anurag Bharadwaj, MD, DM, said in an interview.

“Although there are studies which attribute increased risk of cancer to different DMARDs [disease-modifying antirheumatic drugs] and biologics like TNF, but on other hand, it’s maybe that we are giving these drugs to patients who have got more serious immunological disease,” suggested Bharadwaj, who serves as the clinical lead for rheumatology at Basildon (England) Hospital, Mid & South Essex Foundation Trust.

“So, a possibility may be that the more severe or the more active the immunological inflammatory disease, the higher the chance of cancer, and these are the patients who go for the stronger medications,” Dr. Bharadwaj said.

There is an “immunological window of opportunity” when treating these inflammatory diseases, said Dr. Bharadwaj, noting that the first few months of treatment are vital. “For all immunological diseases, the more quickly you bring the immunological abnormality down, the chances of long-term complications go down, including [possibly that the] chances of cancer go down, chances of cardiovascular disease go down, and chances of lung disease go down. Hit it early, hit it hard.”

Concern over a possible higher risk for cancer with JAK inhibitors than with TNF inhibitors was raised following the release of data from the ORAL Surveillance trial, a postmarketing trial of tofacitinib (Xeljanz) that had been mandated by the Food and Drug Administration.

“This was a study looking at the coprimary endpoints of malignancy and major adverse cardiovascular events, and it was enriched with patients over the age of 50, with one additional cardiac risk factor, designed to amplify the detection of these rare events,” Dr. Stovin said.

“There was a signal of an increased risk of malignancy in the tofacitinib group, and this led to the FDA issuing a [boxed warning for all licensed JAK inhibitors] at that time,” he added.

Dr. Stovin and colleagues aimed to determine what, if any, cancer risk was associated with all available JAK inhibitors relative to placebo, TNF inhibitors, and methotrexate.

In all, data from 62 randomized controlled trials and 14 long-term extension studies were included in the meta-analysis, accounting for 82,366 patient years of follow-up. The JAK inhibitors analyzed included tofacitinib, baricitinib (Olumiant), upadacitinib (Rinvoq), filgotinib (Jyseleca), and peficitinib (Smyraf). (Filgotinib and peficitinib have not been approved by the FDA.)

The researchers performed sensitivity analyses that excluded cancers detected within the first 6 months of treatment, the use of higher than licensed JAK inhibitor doses, and patients with non-rheumatoid arthritis diagnoses, but the results remained largely unchanged, Dr. Stovin reported.  

“Perhaps not surprisingly, when we removed ORAL Surveillance” from the analysis comparing JAK inhibitors and TNF inhibitors, “we lost statistical significance,” he said.

“Longitudinal observational data is needed but currently remains limited,” Dr. Stovin concluded.

Dr. Stovin and Dr. Bharadwaj reported no relevant financial relationships. The meta-analysis was independently supported. Dr. Bharadwaj was not involved in the study and provided comment ahead of the presentation.

A version of this article first appeared on Medscape.com.

MANCHESTER, ENGLAND – Janus kinase (JAK) inhibitors may be associated with a higher risk for cancer relative to tumor necrosis factor (TNF) inhibitors, according to a meta-analysis reported at the annual meeting of the British Society for Rheumatology.

Looking at all phase 2, 3, and 4 trials and long-term extension studies across the indications of rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, and atopic dermatitis, the risk ratio for any cancer developing was 1.63 when compared with anti-TNF therapy (95% confidence interval, 1.27-2.09).

Sara Freeman/MDedge News

By comparison, JAK inhibitor use was not significantly associated with any greater risk for cancer than methotrexate (RR, 1.06; 95% confidence interval, 0.58-1.94) or placebo (RR, 1.16; 95% CI, 0.75-1.80).

“Our data suggests that rather than JAK inhibitors necessarily being harmful, it could be more a case of TNF inhibitors being protective,” said Christopher Stovin, MBChB, a specialist registrar in rheumatology at the Princess Royal University Hospital, King’s College Hospital NHS Trust, London.

“We should stress that these are rare events in our study, roughly around 1 in every 100 patient-years of exposure,” Dr. Stovin said.

“Despite having over 80,000 years of patient exposure, the median follow-up duration for JAK inhibitors was still only 118 weeks, which for cancers [that] obviously have long latency periods is still a relatively small duration of time,” the researcher added.

“People worry about the drugs. But there is a possibility that [a] disturbed immune system plays a role per se in development of cancers,” consultant rheumatologist Anurag Bharadwaj, MD, DM, said in an interview.

“Although there are studies which attribute increased risk of cancer to different DMARDs [disease-modifying antirheumatic drugs] and biologics like TNF, but on other hand, it’s maybe that we are giving these drugs to patients who have got more serious immunological disease,” suggested Bharadwaj, who serves as the clinical lead for rheumatology at Basildon (England) Hospital, Mid & South Essex Foundation Trust.

“So, a possibility may be that the more severe or the more active the immunological inflammatory disease, the higher the chance of cancer, and these are the patients who go for the stronger medications,” Dr. Bharadwaj said.

There is an “immunological window of opportunity” when treating these inflammatory diseases, said Dr. Bharadwaj, noting that the first few months of treatment are vital. “For all immunological diseases, the more quickly you bring the immunological abnormality down, the chances of long-term complications go down, including [possibly that the] chances of cancer go down, chances of cardiovascular disease go down, and chances of lung disease go down. Hit it early, hit it hard.”

Concern over a possible higher risk for cancer with JAK inhibitors than with TNF inhibitors was raised following the release of data from the ORAL Surveillance trial, a postmarketing trial of tofacitinib (Xeljanz) that had been mandated by the Food and Drug Administration.

“This was a study looking at the coprimary endpoints of malignancy and major adverse cardiovascular events, and it was enriched with patients over the age of 50, with one additional cardiac risk factor, designed to amplify the detection of these rare events,” Dr. Stovin said.

“There was a signal of an increased risk of malignancy in the tofacitinib group, and this led to the FDA issuing a [boxed warning for all licensed JAK inhibitors] at that time,” he added.

Dr. Stovin and colleagues aimed to determine what, if any, cancer risk was associated with all available JAK inhibitors relative to placebo, TNF inhibitors, and methotrexate.

In all, data from 62 randomized controlled trials and 14 long-term extension studies were included in the meta-analysis, accounting for 82,366 patient years of follow-up. The JAK inhibitors analyzed included tofacitinib, baricitinib (Olumiant), upadacitinib (Rinvoq), filgotinib (Jyseleca), and peficitinib (Smyraf). (Filgotinib and peficitinib have not been approved by the FDA.)

The researchers performed sensitivity analyses that excluded cancers detected within the first 6 months of treatment, the use of higher than licensed JAK inhibitor doses, and patients with non-rheumatoid arthritis diagnoses, but the results remained largely unchanged, Dr. Stovin reported.  

“Perhaps not surprisingly, when we removed ORAL Surveillance” from the analysis comparing JAK inhibitors and TNF inhibitors, “we lost statistical significance,” he said.

“Longitudinal observational data is needed but currently remains limited,” Dr. Stovin concluded.

Dr. Stovin and Dr. Bharadwaj reported no relevant financial relationships. The meta-analysis was independently supported. Dr. Bharadwaj was not involved in the study and provided comment ahead of the presentation.

A version of this article first appeared on Medscape.com.

MANCHESTER, ENGLAND – Janus kinase (JAK) inhibitors may be associated with a higher risk for cancer relative to tumor necrosis factor (TNF) inhibitors, according to a meta-analysis reported at the annual meeting of the British Society for Rheumatology.

Looking at all phase 2, 3, and 4 trials and long-term extension studies across the indications of rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, and atopic dermatitis, the risk ratio for any cancer developing was 1.63 when compared with anti-TNF therapy (95% confidence interval, 1.27-2.09).

Sara Freeman/MDedge News

By comparison, JAK inhibitor use was not significantly associated with any greater risk for cancer than methotrexate (RR, 1.06; 95% confidence interval, 0.58-1.94) or placebo (RR, 1.16; 95% CI, 0.75-1.80).

“Our data suggests that rather than JAK inhibitors necessarily being harmful, it could be more a case of TNF inhibitors being protective,” said Christopher Stovin, MBChB, a specialist registrar in rheumatology at the Princess Royal University Hospital, King’s College Hospital NHS Trust, London.

“We should stress that these are rare events in our study, roughly around 1 in every 100 patient-years of exposure,” Dr. Stovin said.

“Despite having over 80,000 years of patient exposure, the median follow-up duration for JAK inhibitors was still only 118 weeks, which for cancers [that] obviously have long latency periods is still a relatively small duration of time,” the researcher added.

“People worry about the drugs. But there is a possibility that [a] disturbed immune system plays a role per se in development of cancers,” consultant rheumatologist Anurag Bharadwaj, MD, DM, said in an interview.

“Although there are studies which attribute increased risk of cancer to different DMARDs [disease-modifying antirheumatic drugs] and biologics like TNF, but on other hand, it’s maybe that we are giving these drugs to patients who have got more serious immunological disease,” suggested Bharadwaj, who serves as the clinical lead for rheumatology at Basildon (England) Hospital, Mid & South Essex Foundation Trust.

“So, a possibility may be that the more severe or the more active the immunological inflammatory disease, the higher the chance of cancer, and these are the patients who go for the stronger medications,” Dr. Bharadwaj said.

There is an “immunological window of opportunity” when treating these inflammatory diseases, said Dr. Bharadwaj, noting that the first few months of treatment are vital. “For all immunological diseases, the more quickly you bring the immunological abnormality down, the chances of long-term complications go down, including [possibly that the] chances of cancer go down, chances of cardiovascular disease go down, and chances of lung disease go down. Hit it early, hit it hard.”

Concern over a possible higher risk for cancer with JAK inhibitors than with TNF inhibitors was raised following the release of data from the ORAL Surveillance trial, a postmarketing trial of tofacitinib (Xeljanz) that had been mandated by the Food and Drug Administration.

“This was a study looking at the coprimary endpoints of malignancy and major adverse cardiovascular events, and it was enriched with patients over the age of 50, with one additional cardiac risk factor, designed to amplify the detection of these rare events,” Dr. Stovin said.

“There was a signal of an increased risk of malignancy in the tofacitinib group, and this led to the FDA issuing a [boxed warning for all licensed JAK inhibitors] at that time,” he added.

Dr. Stovin and colleagues aimed to determine what, if any, cancer risk was associated with all available JAK inhibitors relative to placebo, TNF inhibitors, and methotrexate.

In all, data from 62 randomized controlled trials and 14 long-term extension studies were included in the meta-analysis, accounting for 82,366 patient years of follow-up. The JAK inhibitors analyzed included tofacitinib, baricitinib (Olumiant), upadacitinib (Rinvoq), filgotinib (Jyseleca), and peficitinib (Smyraf). (Filgotinib and peficitinib have not been approved by the FDA.)

The researchers performed sensitivity analyses that excluded cancers detected within the first 6 months of treatment, the use of higher than licensed JAK inhibitor doses, and patients with non-rheumatoid arthritis diagnoses, but the results remained largely unchanged, Dr. Stovin reported.  

“Perhaps not surprisingly, when we removed ORAL Surveillance” from the analysis comparing JAK inhibitors and TNF inhibitors, “we lost statistical significance,” he said.

“Longitudinal observational data is needed but currently remains limited,” Dr. Stovin concluded.

Dr. Stovin and Dr. Bharadwaj reported no relevant financial relationships. The meta-analysis was independently supported. Dr. Bharadwaj was not involved in the study and provided comment ahead of the presentation.

A version of this article first appeared on Medscape.com.

MANCHESTER, ENGLAND – Rheumatoid arthritis patients are no more likely to have a heart attack if they are treated with an interleukin-6 inhibitor (IL-6i) than if they are treated with a tumor necrosis factor inhibitor (TNFi), according to data presented at the British Society for Rheumatology annual meeting.

Results of a large analysis from the long-running British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA) found no statistical difference in the rate of myocardial infarction (MI), considering treatment in almost 21,000 patients. The overall propensity-score adjusted hazard ratio for MI risk comparing TNFi and IL-6i was 0.77, but the 95% confidence interval crossed the line for statistical significance.

“This result reassures patients and clinical teams about the long-term treatment effects on myocardial infarction in a real-world setting,” said Tian Zixing, a PhD student at the University of Manchester (England).

Sara Freeman/MDedge News

“Patients with rheumatoid arthritis have an increased risk of myocardial infarction, compared to the general population,” Ms. Tian explained. However, this risk has been “considerably improved” with biologic treatment of rheumatoid arthritis, notably with the TNFi drugs vs. nonbiologic disease-modifying antirheumatic drugs.

The reasoning behind the current analysis was to see if there was any risk associated with IL-6i, as these drugs have been noted to increase low-density cholesterol levels, which in turn can raise the risk for MI.

The study population consisted of all patients registered in the BSRBR-RA over the past 20 years who had started treatment with one of the many TNFi drugs available in the UK – adalimumab (Humira and biosimilars), etanercept (Enbrel), infliximab (Remicade and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi) – or the two available drugs that target the effects of IL-6 – tocilizumab (RoActemra, but Actemra in the U.S.), which targets IL-6 itself, and sarilumab (Kevzara), which targets the IL-6 receptor.

Clinical follow-up forms, death certificates, and patient reports confirmed by the clinical team were used to identify patients who experienced a MI, but only MIs that occurred while on treatment were counted.

More than 30,000 lines of therapy in 20,898 patients were recorded. Ms. Tian noted that most (> 90%) patients had been treated with a TNFi across all lines of therapy.

“It is very important to consider the treatment sequence,” she said. “Most patients start first-line treatment with a TNF inhibitor, with only a few patients starting an IL-6 inhibitor,” she noted. “IL-6 inhibitors are more commonly used in the later stages of disease, when more cardiovascular risk factors have accumulated.”

Thus, to ensure that the MI risk was fairly evaluated, the statistical analyses compared TNFi and IL-6i according to the line of treatment. “That means only patients on their first-line treatment will be compared to each other, and only those on their second-line treatment will be compared to each other, and so on,” Ms. Tian explained.

Baseline characteristics were broadly similar for patients treated with TNFi and IL-6i drugs, except for hyperlipidemia, which was higher in patients treated with an IL-6i. Nevertheless, there was no suggestion of any difference in the MI rates after adjustment for cardiovascular risk factors.

There are a lot of strengths to these data, but of course the possibilities of residual confounding and confounding by indication exist, Ms. Tian said. There were also missing data that had to be imputed.

“There has been quite a bit around interleukin-1 blockers being cardiovascular protective,” observed Kenneth Baker, MBChB, PhD, who chaired the RA oral abstracts session during which Ms. Tian presented the findings.

“IL-6 is quite good at suppressing CRP [C-reactive protein],” added Dr. Baker, a senior clinical research fellow at Newcastle University and honorary consultant rheumatologist at Freeman Hospital, both in Newcastle upon Tyne, England.

“You’ve hypothesized or extrapolated that the differences in the lipid levels may not be relevant,” he said to Ms. Tian, “but do you think there might be an extra element going on here?” Maybe IL-6i drugs such as tocilizumab are better at suppressing inflammation, and that counterbalances the effects on lipids, he suggested.

Ms. Tian and Dr. Baker disclosed no relevant financial relationships. The BSRBR-RA is managed by the University of Manchester on behalf of the British Society for Rheumatology. The registry is supported by funding from multiple pharmaceutical companies, including AbbVie, Amgen, Celltrion Healthcare, Eli Lilly, Galapagos, Pfizer, Samsung Bioepis, and Sanofi, and in the past Hospira, Merck Sharp & Dohme, Roche, Sandoz, SOBI, and UCB.

A version of this article originally appeared on Medscape.com.

MANCHESTER, ENGLAND – Rheumatoid arthritis patients are no more likely to have a heart attack if they are treated with an interleukin-6 inhibitor (IL-6i) than if they are treated with a tumor necrosis factor inhibitor (TNFi), according to data presented at the British Society for Rheumatology annual meeting.

Results of a large analysis from the long-running British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA) found no statistical difference in the rate of myocardial infarction (MI), considering treatment in almost 21,000 patients. The overall propensity-score adjusted hazard ratio for MI risk comparing TNFi and IL-6i was 0.77, but the 95% confidence interval crossed the line for statistical significance.

“This result reassures patients and clinical teams about the long-term treatment effects on myocardial infarction in a real-world setting,” said Tian Zixing, a PhD student at the University of Manchester (England).

Sara Freeman/MDedge News

“Patients with rheumatoid arthritis have an increased risk of myocardial infarction, compared to the general population,” Ms. Tian explained. However, this risk has been “considerably improved” with biologic treatment of rheumatoid arthritis, notably with the TNFi drugs vs. nonbiologic disease-modifying antirheumatic drugs.

The reasoning behind the current analysis was to see if there was any risk associated with IL-6i, as these drugs have been noted to increase low-density cholesterol levels, which in turn can raise the risk for MI.

The study population consisted of all patients registered in the BSRBR-RA over the past 20 years who had started treatment with one of the many TNFi drugs available in the UK – adalimumab (Humira and biosimilars), etanercept (Enbrel), infliximab (Remicade and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi) – or the two available drugs that target the effects of IL-6 – tocilizumab (RoActemra, but Actemra in the U.S.), which targets IL-6 itself, and sarilumab (Kevzara), which targets the IL-6 receptor.

Clinical follow-up forms, death certificates, and patient reports confirmed by the clinical team were used to identify patients who experienced a MI, but only MIs that occurred while on treatment were counted.

More than 30,000 lines of therapy in 20,898 patients were recorded. Ms. Tian noted that most (> 90%) patients had been treated with a TNFi across all lines of therapy.

“It is very important to consider the treatment sequence,” she said. “Most patients start first-line treatment with a TNF inhibitor, with only a few patients starting an IL-6 inhibitor,” she noted. “IL-6 inhibitors are more commonly used in the later stages of disease, when more cardiovascular risk factors have accumulated.”

Thus, to ensure that the MI risk was fairly evaluated, the statistical analyses compared TNFi and IL-6i according to the line of treatment. “That means only patients on their first-line treatment will be compared to each other, and only those on their second-line treatment will be compared to each other, and so on,” Ms. Tian explained.

Baseline characteristics were broadly similar for patients treated with TNFi and IL-6i drugs, except for hyperlipidemia, which was higher in patients treated with an IL-6i. Nevertheless, there was no suggestion of any difference in the MI rates after adjustment for cardiovascular risk factors.

There are a lot of strengths to these data, but of course the possibilities of residual confounding and confounding by indication exist, Ms. Tian said. There were also missing data that had to be imputed.

“There has been quite a bit around interleukin-1 blockers being cardiovascular protective,” observed Kenneth Baker, MBChB, PhD, who chaired the RA oral abstracts session during which Ms. Tian presented the findings.

“IL-6 is quite good at suppressing CRP [C-reactive protein],” added Dr. Baker, a senior clinical research fellow at Newcastle University and honorary consultant rheumatologist at Freeman Hospital, both in Newcastle upon Tyne, England.

“You’ve hypothesized or extrapolated that the differences in the lipid levels may not be relevant,” he said to Ms. Tian, “but do you think there might be an extra element going on here?” Maybe IL-6i drugs such as tocilizumab are better at suppressing inflammation, and that counterbalances the effects on lipids, he suggested.

Ms. Tian and Dr. Baker disclosed no relevant financial relationships. The BSRBR-RA is managed by the University of Manchester on behalf of the British Society for Rheumatology. The registry is supported by funding from multiple pharmaceutical companies, including AbbVie, Amgen, Celltrion Healthcare, Eli Lilly, Galapagos, Pfizer, Samsung Bioepis, and Sanofi, and in the past Hospira, Merck Sharp & Dohme, Roche, Sandoz, SOBI, and UCB.

A version of this article originally appeared on Medscape.com.

MANCHESTER, ENGLAND – Rheumatoid arthritis patients are no more likely to have a heart attack if they are treated with an interleukin-6 inhibitor (IL-6i) than if they are treated with a tumor necrosis factor inhibitor (TNFi), according to data presented at the British Society for Rheumatology annual meeting.

Results of a large analysis from the long-running British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA) found no statistical difference in the rate of myocardial infarction (MI), considering treatment in almost 21,000 patients. The overall propensity-score adjusted hazard ratio for MI risk comparing TNFi and IL-6i was 0.77, but the 95% confidence interval crossed the line for statistical significance.

“This result reassures patients and clinical teams about the long-term treatment effects on myocardial infarction in a real-world setting,” said Tian Zixing, a PhD student at the University of Manchester (England).

Sara Freeman/MDedge News

“Patients with rheumatoid arthritis have an increased risk of myocardial infarction, compared to the general population,” Ms. Tian explained. However, this risk has been “considerably improved” with biologic treatment of rheumatoid arthritis, notably with the TNFi drugs vs. nonbiologic disease-modifying antirheumatic drugs.

The reasoning behind the current analysis was to see if there was any risk associated with IL-6i, as these drugs have been noted to increase low-density cholesterol levels, which in turn can raise the risk for MI.

The study population consisted of all patients registered in the BSRBR-RA over the past 20 years who had started treatment with one of the many TNFi drugs available in the UK – adalimumab (Humira and biosimilars), etanercept (Enbrel), infliximab (Remicade and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi) – or the two available drugs that target the effects of IL-6 – tocilizumab (RoActemra, but Actemra in the U.S.), which targets IL-6 itself, and sarilumab (Kevzara), which targets the IL-6 receptor.

Clinical follow-up forms, death certificates, and patient reports confirmed by the clinical team were used to identify patients who experienced a MI, but only MIs that occurred while on treatment were counted.

More than 30,000 lines of therapy in 20,898 patients were recorded. Ms. Tian noted that most (> 90%) patients had been treated with a TNFi across all lines of therapy.

“It is very important to consider the treatment sequence,” she said. “Most patients start first-line treatment with a TNF inhibitor, with only a few patients starting an IL-6 inhibitor,” she noted. “IL-6 inhibitors are more commonly used in the later stages of disease, when more cardiovascular risk factors have accumulated.”

Thus, to ensure that the MI risk was fairly evaluated, the statistical analyses compared TNFi and IL-6i according to the line of treatment. “That means only patients on their first-line treatment will be compared to each other, and only those on their second-line treatment will be compared to each other, and so on,” Ms. Tian explained.

Baseline characteristics were broadly similar for patients treated with TNFi and IL-6i drugs, except for hyperlipidemia, which was higher in patients treated with an IL-6i. Nevertheless, there was no suggestion of any difference in the MI rates after adjustment for cardiovascular risk factors.

There are a lot of strengths to these data, but of course the possibilities of residual confounding and confounding by indication exist, Ms. Tian said. There were also missing data that had to be imputed.

“There has been quite a bit around interleukin-1 blockers being cardiovascular protective,” observed Kenneth Baker, MBChB, PhD, who chaired the RA oral abstracts session during which Ms. Tian presented the findings.

“IL-6 is quite good at suppressing CRP [C-reactive protein],” added Dr. Baker, a senior clinical research fellow at Newcastle University and honorary consultant rheumatologist at Freeman Hospital, both in Newcastle upon Tyne, England.

“You’ve hypothesized or extrapolated that the differences in the lipid levels may not be relevant,” he said to Ms. Tian, “but do you think there might be an extra element going on here?” Maybe IL-6i drugs such as tocilizumab are better at suppressing inflammation, and that counterbalances the effects on lipids, he suggested.

Ms. Tian and Dr. Baker disclosed no relevant financial relationships. The BSRBR-RA is managed by the University of Manchester on behalf of the British Society for Rheumatology. The registry is supported by funding from multiple pharmaceutical companies, including AbbVie, Amgen, Celltrion Healthcare, Eli Lilly, Galapagos, Pfizer, Samsung Bioepis, and Sanofi, and in the past Hospira, Merck Sharp & Dohme, Roche, Sandoz, SOBI, and UCB.

A version of this article originally appeared on Medscape.com.

Patients taking metformin for type 2 diabetes had a lower risk of developing osteoarthritis than did patients taking a sulfonylurea, according to a cohort study published in JAMA Network Open. The findings jibe with those seen in a 2022 systematic review of preclinical and observational human studies finding potentially protective effects of metformin on osteoarthritis.

“Our study provides further, robust epidemiological evidence that metformin may be associated with protection in the development and progression of osteoarthritis in individuals with type 2 diabetes,” wrote Matthew C. Baker, MD, MS, an assistant professor of medicine in immunology and rheumatology at Stanford (Calif.) University, and his colleagues.

Thinglass/iStock Editorial/Getty Images

The findings also fit with the results of a poster presented at the Osteoarthritis Research Society International 2023 World Congress, although that abstract’s findings did not reach statistical significance.

In the published study, the researchers analyzed deidentified claims data from Optum’s Clinformatics Data Mart Database between December 2003 and December 2019. The database includes more than 15 million people with private insurance or Medicare Advantage Part D but does not include people with Medicaid, thereby excluding people from lower socioeconomic groups.

The researchers included all patients who were at least 40 years old, had type 2 diabetes, were taking metformin, and had been enrolled in the database for at least 1 uninterrupted year. They excluded anyone with type 1 diabetes or a prior diagnosis of osteoarthritis, inflammatory arthritis, or joint replacement. The authors then compared the incidence of osteoarthritis and joint replacement in these 20,937 participants to 20,937 control participants who were taking a sulfonylurea, matched to those taking metformin on the basis of age, sex, race, a comorbidity score, and duration of treatment. More than half the overall population (58%) was male with an average age of 62.

Patients needed to be on either drug for at least 3 months, but those who were initially treated with metformin before later taking a sulfonylurea could also be included and contribute to both groups. Those who first took a sulfonylurea and later switched to metformin were included only for the sulfonylurea group and censored after their switch to ensure the sulfonylurea group had enough participants. The comparison was further adjusted for age, sex, race, ethnicity, geographic region, education, comorbidities, and outpatient visit frequency.

The results revealed that those who were taking metformin were 24% less likely to develop osteoarthritis at least 3 months after starting the medication than were those taking a sulfonylurea (P < .001). The rate of joint replacements was not significantly different between those taking metformin and those taking a sulfonylurea. These two results did not change in a sensitivity analysis that compared patients who only ever took metformin or a sulfonylurea (as opposed to those who took one drug before switching to the other).

“When stratified by prior exposure to metformin within the sulfonylurea group, the observed benefit associated with metformin ... was attenuated in the people treated with a sulfonylurea with prior exposure to metformin, compared with those treated with a sulfonylurea with no prior exposure to metformin,” the authors further reported. A possible reason for this finding is that those taking a sulfonylurea after having previously taken metformin gained some protection from the earlier metformin exposure, the authors hypothesized.

This observational study could not show a causative effect from the metformin, but the researchers speculated on potential mechanisms if a causative effect were present, based on past research.

”Several preclinical studies have suggested a protective association of metformin in osteoarthritis through activating AMP-activated protein kinase signaling, decreasing the level of matrix metalloproteinase, increasing autophagy and reducing chondrocyte apoptosis, and augmenting chondroprotective and anti-inflammatory properties of mesenchymal stem cells,” the authors wrote.

Among this study’s limitations, however, was the lack of data on body mass index, which is associated with osteoarthritis in the literature and may differ between patients taking metformin versus a sulfonylurea. The researchers also did not have data on physical activity or a history of trauma to the joints, though there’s no reason to think these rates might differ between those taking one or the other medication.

Another substantial limitation is that all patients had type 2 diabetes, making it impossible to determine whether a similar protective effect from metformin might exist in people without diabetes.

Nonsignificant lower risk for posttraumatic knee osteoarthritis

Similar to the published study, the OARSI poster compared 5-year odds of incident osteoarthritis or total knee replacement surgery between patients taking metformin and those taking sulfonylureas, but it focused on younger patients, aged 18-40 years, who underwent anterior cruciate ligament or meniscus surgery.

Using data from MarketScan commercial insurance claims databases between 2006 and 2020, the authors identified 2,376 participants who were taking metformin or a sulfonylurea when they underwent their surgery or began taking it in the 6 months after their surgery. More than half the participants were female (57%) with an average age of 35.

Within 5 years, 10.8% of those taking metformin developed osteoarthritis, compared with 17.9% of those taking a sulfonylurea. In addition, 3% of those taking metformin underwent a total knee replacement, compared with 5.3% of those taking a sulfonylurea. After adjustment for age, sex, obesity, and a history of chronic kidney disease, liver disease, and depression, however, both risk difference and odds ratios were not statistically significant.

Risk of osteoarthritis was 17% lower in patients taking metformin (95% confidence interval, –0.18 to 0.09), whose odds of osteoarthritis were approximately half the odds of those taking a sulfonylurea (OR, 0.5; 95% CI, 0.21-1.67). Risk of a total knee replacement was 10% lower in metformin users (95% CI, –0.28 to 0.08) with a similar reduction in odds, compared with those taking a sulfonylurea (OR, 0.53; 95% CI, 0.2-1.44).

In this study, the researchers did not specifically determine whether the participants were diagnosed with diabetes, but they assumed all, or at least most, were, according to S. Reza Jafarzadeh, PhD, DVM, an assistant professor of medicine at Boston University.

“The goal was not to only focus on the diabetes population, but on people who received that exposure [of metformin or sulfonylureas],” Dr. Jafarzadeh said in an interview. Dr. Jafarzadeh noted that a larger randomized controlled trial is underway to look at whether metformin reduces the risk of osteoarthritis independent of whether a patient has diabetes.

The published study was funded by grants from the National Institutes of Health, the Department of Veterans Affairs, and Stanford University, and the authors reported no disclosures. The poster at OARSI was funded by NIH and the Arthritis Foundation, and the authors reported no disclosures.

Patients taking metformin for type 2 diabetes had a lower risk of developing osteoarthritis than did patients taking a sulfonylurea, according to a cohort study published in JAMA Network Open. The findings jibe with those seen in a 2022 systematic review of preclinical and observational human studies finding potentially protective effects of metformin on osteoarthritis.

“Our study provides further, robust epidemiological evidence that metformin may be associated with protection in the development and progression of osteoarthritis in individuals with type 2 diabetes,” wrote Matthew C. Baker, MD, MS, an assistant professor of medicine in immunology and rheumatology at Stanford (Calif.) University, and his colleagues.

Thinglass/iStock Editorial/Getty Images

The findings also fit with the results of a poster presented at the Osteoarthritis Research Society International 2023 World Congress, although that abstract’s findings did not reach statistical significance.

In the published study, the researchers analyzed deidentified claims data from Optum’s Clinformatics Data Mart Database between December 2003 and December 2019. The database includes more than 15 million people with private insurance or Medicare Advantage Part D but does not include people with Medicaid, thereby excluding people from lower socioeconomic groups.

The researchers included all patients who were at least 40 years old, had type 2 diabetes, were taking metformin, and had been enrolled in the database for at least 1 uninterrupted year. They excluded anyone with type 1 diabetes or a prior diagnosis of osteoarthritis, inflammatory arthritis, or joint replacement. The authors then compared the incidence of osteoarthritis and joint replacement in these 20,937 participants to 20,937 control participants who were taking a sulfonylurea, matched to those taking metformin on the basis of age, sex, race, a comorbidity score, and duration of treatment. More than half the overall population (58%) was male with an average age of 62.

Patients needed to be on either drug for at least 3 months, but those who were initially treated with metformin before later taking a sulfonylurea could also be included and contribute to both groups. Those who first took a sulfonylurea and later switched to metformin were included only for the sulfonylurea group and censored after their switch to ensure the sulfonylurea group had enough participants. The comparison was further adjusted for age, sex, race, ethnicity, geographic region, education, comorbidities, and outpatient visit frequency.

The results revealed that those who were taking metformin were 24% less likely to develop osteoarthritis at least 3 months after starting the medication than were those taking a sulfonylurea (P < .001). The rate of joint replacements was not significantly different between those taking metformin and those taking a sulfonylurea. These two results did not change in a sensitivity analysis that compared patients who only ever took metformin or a sulfonylurea (as opposed to those who took one drug before switching to the other).

“When stratified by prior exposure to metformin within the sulfonylurea group, the observed benefit associated with metformin ... was attenuated in the people treated with a sulfonylurea with prior exposure to metformin, compared with those treated with a sulfonylurea with no prior exposure to metformin,” the authors further reported. A possible reason for this finding is that those taking a sulfonylurea after having previously taken metformin gained some protection from the earlier metformin exposure, the authors hypothesized.

This observational study could not show a causative effect from the metformin, but the researchers speculated on potential mechanisms if a causative effect were present, based on past research.

”Several preclinical studies have suggested a protective association of metformin in osteoarthritis through activating AMP-activated protein kinase signaling, decreasing the level of matrix metalloproteinase, increasing autophagy and reducing chondrocyte apoptosis, and augmenting chondroprotective and anti-inflammatory properties of mesenchymal stem cells,” the authors wrote.

Among this study’s limitations, however, was the lack of data on body mass index, which is associated with osteoarthritis in the literature and may differ between patients taking metformin versus a sulfonylurea. The researchers also did not have data on physical activity or a history of trauma to the joints, though there’s no reason to think these rates might differ between those taking one or the other medication.

Another substantial limitation is that all patients had type 2 diabetes, making it impossible to determine whether a similar protective effect from metformin might exist in people without diabetes.

Nonsignificant lower risk for posttraumatic knee osteoarthritis

Similar to the published study, the OARSI poster compared 5-year odds of incident osteoarthritis or total knee replacement surgery between patients taking metformin and those taking sulfonylureas, but it focused on younger patients, aged 18-40 years, who underwent anterior cruciate ligament or meniscus surgery.

Using data from MarketScan commercial insurance claims databases between 2006 and 2020, the authors identified 2,376 participants who were taking metformin or a sulfonylurea when they underwent their surgery or began taking it in the 6 months after their surgery. More than half the participants were female (57%) with an average age of 35.

Within 5 years, 10.8% of those taking metformin developed osteoarthritis, compared with 17.9% of those taking a sulfonylurea. In addition, 3% of those taking metformin underwent a total knee replacement, compared with 5.3% of those taking a sulfonylurea. After adjustment for age, sex, obesity, and a history of chronic kidney disease, liver disease, and depression, however, both risk difference and odds ratios were not statistically significant.

Risk of osteoarthritis was 17% lower in patients taking metformin (95% confidence interval, –0.18 to 0.09), whose odds of osteoarthritis were approximately half the odds of those taking a sulfonylurea (OR, 0.5; 95% CI, 0.21-1.67). Risk of a total knee replacement was 10% lower in metformin users (95% CI, –0.28 to 0.08) with a similar reduction in odds, compared with those taking a sulfonylurea (OR, 0.53; 95% CI, 0.2-1.44).

In this study, the researchers did not specifically determine whether the participants were diagnosed with diabetes, but they assumed all, or at least most, were, according to S. Reza Jafarzadeh, PhD, DVM, an assistant professor of medicine at Boston University.

“The goal was not to only focus on the diabetes population, but on people who received that exposure [of metformin or sulfonylureas],” Dr. Jafarzadeh said in an interview. Dr. Jafarzadeh noted that a larger randomized controlled trial is underway to look at whether metformin reduces the risk of osteoarthritis independent of whether a patient has diabetes.

The published study was funded by grants from the National Institutes of Health, the Department of Veterans Affairs, and Stanford University, and the authors reported no disclosures. The poster at OARSI was funded by NIH and the Arthritis Foundation, and the authors reported no disclosures.

Patients taking metformin for type 2 diabetes had a lower risk of developing osteoarthritis than did patients taking a sulfonylurea, according to a cohort study published in JAMA Network Open. The findings jibe with those seen in a 2022 systematic review of preclinical and observational human studies finding potentially protective effects of metformin on osteoarthritis.

“Our study provides further, robust epidemiological evidence that metformin may be associated with protection in the development and progression of osteoarthritis in individuals with type 2 diabetes,” wrote Matthew C. Baker, MD, MS, an assistant professor of medicine in immunology and rheumatology at Stanford (Calif.) University, and his colleagues.

Thinglass/iStock Editorial/Getty Images

The findings also fit with the results of a poster presented at the Osteoarthritis Research Society International 2023 World Congress, although that abstract’s findings did not reach statistical significance.

In the published study, the researchers analyzed deidentified claims data from Optum’s Clinformatics Data Mart Database between December 2003 and December 2019. The database includes more than 15 million people with private insurance or Medicare Advantage Part D but does not include people with Medicaid, thereby excluding people from lower socioeconomic groups.

The researchers included all patients who were at least 40 years old, had type 2 diabetes, were taking metformin, and had been enrolled in the database for at least 1 uninterrupted year. They excluded anyone with type 1 diabetes or a prior diagnosis of osteoarthritis, inflammatory arthritis, or joint replacement. The authors then compared the incidence of osteoarthritis and joint replacement in these 20,937 participants to 20,937 control participants who were taking a sulfonylurea, matched to those taking metformin on the basis of age, sex, race, a comorbidity score, and duration of treatment. More than half the overall population (58%) was male with an average age of 62.

Patients needed to be on either drug for at least 3 months, but those who were initially treated with metformin before later taking a sulfonylurea could also be included and contribute to both groups. Those who first took a sulfonylurea and later switched to metformin were included only for the sulfonylurea group and censored after their switch to ensure the sulfonylurea group had enough participants. The comparison was further adjusted for age, sex, race, ethnicity, geographic region, education, comorbidities, and outpatient visit frequency.

The results revealed that those who were taking metformin were 24% less likely to develop osteoarthritis at least 3 months after starting the medication than were those taking a sulfonylurea (P < .001). The rate of joint replacements was not significantly different between those taking metformin and those taking a sulfonylurea. These two results did not change in a sensitivity analysis that compared patients who only ever took metformin or a sulfonylurea (as opposed to those who took one drug before switching to the other).

“When stratified by prior exposure to metformin within the sulfonylurea group, the observed benefit associated with metformin ... was attenuated in the people treated with a sulfonylurea with prior exposure to metformin, compared with those treated with a sulfonylurea with no prior exposure to metformin,” the authors further reported. A possible reason for this finding is that those taking a sulfonylurea after having previously taken metformin gained some protection from the earlier metformin exposure, the authors hypothesized.

This observational study could not show a causative effect from the metformin, but the researchers speculated on potential mechanisms if a causative effect were present, based on past research.

”Several preclinical studies have suggested a protective association of metformin in osteoarthritis through activating AMP-activated protein kinase signaling, decreasing the level of matrix metalloproteinase, increasing autophagy and reducing chondrocyte apoptosis, and augmenting chondroprotective and anti-inflammatory properties of mesenchymal stem cells,” the authors wrote.

Among this study’s limitations, however, was the lack of data on body mass index, which is associated with osteoarthritis in the literature and may differ between patients taking metformin versus a sulfonylurea. The researchers also did not have data on physical activity or a history of trauma to the joints, though there’s no reason to think these rates might differ between those taking one or the other medication.

Another substantial limitation is that all patients had type 2 diabetes, making it impossible to determine whether a similar protective effect from metformin might exist in people without diabetes.

Nonsignificant lower risk for posttraumatic knee osteoarthritis

Similar to the published study, the OARSI poster compared 5-year odds of incident osteoarthritis or total knee replacement surgery between patients taking metformin and those taking sulfonylureas, but it focused on younger patients, aged 18-40 years, who underwent anterior cruciate ligament or meniscus surgery.

Using data from MarketScan commercial insurance claims databases between 2006 and 2020, the authors identified 2,376 participants who were taking metformin or a sulfonylurea when they underwent their surgery or began taking it in the 6 months after their surgery. More than half the participants were female (57%) with an average age of 35.

Within 5 years, 10.8% of those taking metformin developed osteoarthritis, compared with 17.9% of those taking a sulfonylurea. In addition, 3% of those taking metformin underwent a total knee replacement, compared with 5.3% of those taking a sulfonylurea. After adjustment for age, sex, obesity, and a history of chronic kidney disease, liver disease, and depression, however, both risk difference and odds ratios were not statistically significant.

Risk of osteoarthritis was 17% lower in patients taking metformin (95% confidence interval, –0.18 to 0.09), whose odds of osteoarthritis were approximately half the odds of those taking a sulfonylurea (OR, 0.5; 95% CI, 0.21-1.67). Risk of a total knee replacement was 10% lower in metformin users (95% CI, –0.28 to 0.08) with a similar reduction in odds, compared with those taking a sulfonylurea (OR, 0.53; 95% CI, 0.2-1.44).

In this study, the researchers did not specifically determine whether the participants were diagnosed with diabetes, but they assumed all, or at least most, were, according to S. Reza Jafarzadeh, PhD, DVM, an assistant professor of medicine at Boston University.

“The goal was not to only focus on the diabetes population, but on people who received that exposure [of metformin or sulfonylureas],” Dr. Jafarzadeh said in an interview. Dr. Jafarzadeh noted that a larger randomized controlled trial is underway to look at whether metformin reduces the risk of osteoarthritis independent of whether a patient has diabetes.

The published study was funded by grants from the National Institutes of Health, the Department of Veterans Affairs, and Stanford University, and the authors reported no disclosures. The poster at OARSI was funded by NIH and the Arthritis Foundation, and the authors reported no disclosures.

Nasal damage from cocaine use can be misdiagnosed as a rare, nonthreatening nasal disease, according to researchers from the United Kingdom.

Granulomatosis with polyangiitis (GPA), a disorder which causes inflammation in the nose, sinuses, throat, lungs, and kidneys, can have similar symptoms to cocaine-induced vasculitis, the researchers wrote. Drug testing can help identify patients who have cocaine-induced disease, they argued.

“Patients with destructive nasal lesions, especially young patients, should have urine toxicology performed for cocaine before diagnosing GPA and considering immunosuppressive therapy,” the authors wrote.

The paper was published in Rheumatology Advances in Practice.

Cocaine is the second-most popular drug in the United Kingdom, with 2.0% of people aged 16-59 years reporting using the drug in the past year. In the United States, about 1.7% of people aged 12 years and older (about 4.8 million people) used cocaine in the last 12 months, according to the 2021 National Survey on Drug Use and Health. The drug can cause midline destructive lesions, skin rash, and other vascular problems, and it can also trigger the production of antineutrophil cytoplasmic antibodies (ANCA) that lead to a clinical presentation that mimics GPA, which can make diagnosis more difficult. Treating cocaine-induced disease with immunosuppressant medication can be ineffective if the patient does not stop using the drug, and can have dangerous side effects, previous case studies suggest.

To better understand cocaine-induced disease, researchers conducted a review of patients who visited vasculitis clinics at Queen Elizabeth Hospital in Birmingham, England, and at the Royal Free Hospital in London between 2016 and 2021. They identified 42 patients with GPA-like symptoms who disclosed cocaine use or tested positive for the drug in urine toxicology test. The study included 23 men, 18 women, and 1 individual who did not identify with either gender. The median age was 41 years, and most patients were white.

Of those who underwent drug testing, more than 85% were positive. Nine patients who denied ever using cocaine were positive for the drug and 11 patients who said they were ex-users also tested positive via urine analysis. During clinical examinations, 30 patients had evidence of septal perforation, of which 6 had oronasal fistulas. Most patients’ symptoms were limited to the upper respiratory tract, though 12 did have other systemic symptoms, including skin lesions, joint pain, breathlessness, fatigue, and diplopia. Of the patients who received blood tests for ANCA, 87.5% tested positive for the antibodies.

The researchers noted that patients who continued cocaine use did not see improvement of symptoms, even if they were treated with immunosuppressant drugs.

“The experience in our two different centers suggests that discontinuation of cocaine is required to manage patients and that symptoms will persist despite immunosuppression if there is ongoing cocaine use,” the authors wrote.

“It can feel like chasing your tail at times if you’re trying to treat the inflammation but the real culprit – what’s driving the inflammation – is persistent,” Lindsay S. Lally, MD, a rheumatologist at the Hospital for Special Surgery in New York, said in an interview. She was not involved with the work.

Dr. Lally said the paper had a decent-sized cohort, and “helps us recognize that cocaine use is probably an under-recognized mimic of GPA, even though it’s something we all learn about and talk about.” She added that routine toxicology screening for patients deserves some consideration, though asking patients to complete a drug test could also undermine trust in the doctor-patient relationship. Patients who deny cocaine use may leave the office without providing a urine sample.

If Dr. Lally does suspect cocaine may be the cause of a patient’s systems, having a candid conversation with the patient may have a better chance at getting a patient to open up about their potential drug use. In practice, this means explaining “why it’s so important for me as their partner in this treatment to understand what factors are at play, and how dangerous it could potentially be if I was giving strong immunosuppressive medications [for a condition] that is being induced by a drug,” she said. “I do think that partnership and talking to the patients, at least in many patients, is more helpful than sort of the ‘gotcha’ moment” that can happen with drug testing.

The study authors disclosed no relevant financial relationships. Dr. Lally reported receiving consulting fees from Amgen.

A version of this article first appeared on Medscape.com.

Nasal damage from cocaine use can be misdiagnosed as a rare, nonthreatening nasal disease, according to researchers from the United Kingdom.

Granulomatosis with polyangiitis (GPA), a disorder which causes inflammation in the nose, sinuses, throat, lungs, and kidneys, can have similar symptoms to cocaine-induced vasculitis, the researchers wrote. Drug testing can help identify patients who have cocaine-induced disease, they argued.

“Patients with destructive nasal lesions, especially young patients, should have urine toxicology performed for cocaine before diagnosing GPA and considering immunosuppressive therapy,” the authors wrote.

The paper was published in Rheumatology Advances in Practice.

Cocaine is the second-most popular drug in the United Kingdom, with 2.0% of people aged 16-59 years reporting using the drug in the past year. In the United States, about 1.7% of people aged 12 years and older (about 4.8 million people) used cocaine in the last 12 months, according to the 2021 National Survey on Drug Use and Health. The drug can cause midline destructive lesions, skin rash, and other vascular problems, and it can also trigger the production of antineutrophil cytoplasmic antibodies (ANCA) that lead to a clinical presentation that mimics GPA, which can make diagnosis more difficult. Treating cocaine-induced disease with immunosuppressant medication can be ineffective if the patient does not stop using the drug, and can have dangerous side effects, previous case studies suggest.

To better understand cocaine-induced disease, researchers conducted a review of patients who visited vasculitis clinics at Queen Elizabeth Hospital in Birmingham, England, and at the Royal Free Hospital in London between 2016 and 2021. They identified 42 patients with GPA-like symptoms who disclosed cocaine use or tested positive for the drug in urine toxicology test. The study included 23 men, 18 women, and 1 individual who did not identify with either gender. The median age was 41 years, and most patients were white.

Of those who underwent drug testing, more than 85% were positive. Nine patients who denied ever using cocaine were positive for the drug and 11 patients who said they were ex-users also tested positive via urine analysis. During clinical examinations, 30 patients had evidence of septal perforation, of which 6 had oronasal fistulas. Most patients’ symptoms were limited to the upper respiratory tract, though 12 did have other systemic symptoms, including skin lesions, joint pain, breathlessness, fatigue, and diplopia. Of the patients who received blood tests for ANCA, 87.5% tested positive for the antibodies.

The researchers noted that patients who continued cocaine use did not see improvement of symptoms, even if they were treated with immunosuppressant drugs.

“The experience in our two different centers suggests that discontinuation of cocaine is required to manage patients and that symptoms will persist despite immunosuppression if there is ongoing cocaine use,” the authors wrote.

“It can feel like chasing your tail at times if you’re trying to treat the inflammation but the real culprit – what’s driving the inflammation – is persistent,” Lindsay S. Lally, MD, a rheumatologist at the Hospital for Special Surgery in New York, said in an interview. She was not involved with the work.

Dr. Lally said the paper had a decent-sized cohort, and “helps us recognize that cocaine use is probably an under-recognized mimic of GPA, even though it’s something we all learn about and talk about.” She added that routine toxicology screening for patients deserves some consideration, though asking patients to complete a drug test could also undermine trust in the doctor-patient relationship. Patients who deny cocaine use may leave the office without providing a urine sample.

If Dr. Lally does suspect cocaine may be the cause of a patient’s systems, having a candid conversation with the patient may have a better chance at getting a patient to open up about their potential drug use. In practice, this means explaining “why it’s so important for me as their partner in this treatment to understand what factors are at play, and how dangerous it could potentially be if I was giving strong immunosuppressive medications [for a condition] that is being induced by a drug,” she said. “I do think that partnership and talking to the patients, at least in many patients, is more helpful than sort of the ‘gotcha’ moment” that can happen with drug testing.

The study authors disclosed no relevant financial relationships. Dr. Lally reported receiving consulting fees from Amgen.

A version of this article first appeared on Medscape.com.

Nasal damage from cocaine use can be misdiagnosed as a rare, nonthreatening nasal disease, according to researchers from the United Kingdom.

Granulomatosis with polyangiitis (GPA), a disorder which causes inflammation in the nose, sinuses, throat, lungs, and kidneys, can have similar symptoms to cocaine-induced vasculitis, the researchers wrote. Drug testing can help identify patients who have cocaine-induced disease, they argued.

“Patients with destructive nasal lesions, especially young patients, should have urine toxicology performed for cocaine before diagnosing GPA and considering immunosuppressive therapy,” the authors wrote.

The paper was published in Rheumatology Advances in Practice.

Cocaine is the second-most popular drug in the United Kingdom, with 2.0% of people aged 16-59 years reporting using the drug in the past year. In the United States, about 1.7% of people aged 12 years and older (about 4.8 million people) used cocaine in the last 12 months, according to the 2021 National Survey on Drug Use and Health. The drug can cause midline destructive lesions, skin rash, and other vascular problems, and it can also trigger the production of antineutrophil cytoplasmic antibodies (ANCA) that lead to a clinical presentation that mimics GPA, which can make diagnosis more difficult. Treating cocaine-induced disease with immunosuppressant medication can be ineffective if the patient does not stop using the drug, and can have dangerous side effects, previous case studies suggest.

To better understand cocaine-induced disease, researchers conducted a review of patients who visited vasculitis clinics at Queen Elizabeth Hospital in Birmingham, England, and at the Royal Free Hospital in London between 2016 and 2021. They identified 42 patients with GPA-like symptoms who disclosed cocaine use or tested positive for the drug in urine toxicology test. The study included 23 men, 18 women, and 1 individual who did not identify with either gender. The median age was 41 years, and most patients were white.

Of those who underwent drug testing, more than 85% were positive. Nine patients who denied ever using cocaine were positive for the drug and 11 patients who said they were ex-users also tested positive via urine analysis. During clinical examinations, 30 patients had evidence of septal perforation, of which 6 had oronasal fistulas. Most patients’ symptoms were limited to the upper respiratory tract, though 12 did have other systemic symptoms, including skin lesions, joint pain, breathlessness, fatigue, and diplopia. Of the patients who received blood tests for ANCA, 87.5% tested positive for the antibodies.

The researchers noted that patients who continued cocaine use did not see improvement of symptoms, even if they were treated with immunosuppressant drugs.

“The experience in our two different centers suggests that discontinuation of cocaine is required to manage patients and that symptoms will persist despite immunosuppression if there is ongoing cocaine use,” the authors wrote.

“It can feel like chasing your tail at times if you’re trying to treat the inflammation but the real culprit – what’s driving the inflammation – is persistent,” Lindsay S. Lally, MD, a rheumatologist at the Hospital for Special Surgery in New York, said in an interview. She was not involved with the work.

Dr. Lally said the paper had a decent-sized cohort, and “helps us recognize that cocaine use is probably an under-recognized mimic of GPA, even though it’s something we all learn about and talk about.” She added that routine toxicology screening for patients deserves some consideration, though asking patients to complete a drug test could also undermine trust in the doctor-patient relationship. Patients who deny cocaine use may leave the office without providing a urine sample.

If Dr. Lally does suspect cocaine may be the cause of a patient’s systems, having a candid conversation with the patient may have a better chance at getting a patient to open up about their potential drug use. In practice, this means explaining “why it’s so important for me as their partner in this treatment to understand what factors are at play, and how dangerous it could potentially be if I was giving strong immunosuppressive medications [for a condition] that is being induced by a drug,” she said. “I do think that partnership and talking to the patients, at least in many patients, is more helpful than sort of the ‘gotcha’ moment” that can happen with drug testing.

The study authors disclosed no relevant financial relationships. Dr. Lally reported receiving consulting fees from Amgen.

A version of this article first appeared on Medscape.com.

The investigational interleukin-17A inhibitor izokibep showed higher response rates across a number of symptoms in adults with psoriatic arthritis (PsA) in an extension of its phase 2 trial out to 46 weeks, according to an announcement reporting some of the long-term data by the drug’s developer, Acelyrin.

Izokibep is an antibody mimetic designed to inhibit IL-17A that the company says has “high potency and the potential for robust tissue penetration due to its small molecular size, about one-tenth the size of a monoclonal antibody.”

“Patients want both rapid and meaningful improvement of their symptoms, as well as lasting – and ideally improving – resolution of disease over time. Building on the 16-week data for izokibep reported at EULAR and ACR [American College of Rheumatology] last year, the 46-week data now show not only continued but marked improvements over time in key areas of psoriatic arthritis including joint pain, skin psoriasis, and enthesitis,” Philip J. Mease, MD, director of rheumatology research at the Swedish Medical Center and clinical professor at the University of Washington, both in Seattle, and an investigator in the izokibep PsA program, said in the announcement.

The phase 2 trial tested two doses of izokibep – 40 mg and 80 mg – given by subcutaneous injection every 2 weeks – against placebo in 135 adult patients with active PsA. For inclusion in the trial, patients had to have at least three swollen and at least three tender joints and an inadequate response to prior therapy including NSAIDs, conventional synthetic disease-modifying antirheumatic drugs, or tumor necrosis factor inhibitors. At week 16, the placebo group transitioned to 80 mg izokibep every 2 weeks and the trial treatment period continued for up to 46 weeks.

The trial’s primary endpoint of a 50% or higher level of improvement in ACR response criteria (ACR 50) was achieved by 48% of those on the 40 mg dose at week 16 and by 50% at week 46. For the 80-mg group, this rate rose from 52% to 79%. In the group that went from placebo to 80 mg, the ACR 50 rose from 13% with placebo to 73% with izokibep at week 46.

Resolution of enthesitis, measured by the Leeds Enthesitis Index, among those on the 40 mg dose, was achieved by 63% at week 16 and 83% at week 46, and among those on the 80 mg dose, 88% at week 16 and 89% at week 46. Those on placebo who switched to 80 mg of izokibep at week 16 had an 80% rate of enthesitis resolution at week 46.

Total resolution of skin involvement – 100% clearance of psoriasis based on the Psoriasis Area Severity Index (PASI) – was observed at 46 weeks in 50% of those on 40 mg, 71% of those on 80 mg, and 67% of those on 80 mg after week 16.

In its announcement, Acelyrin did not report withdrawal rates from the study after 16 weeks and through 46 weeks, although the statement said that izokibep “was generally well tolerated through 46 weeks, which is in line with previous trials of izokibep.” The most common adverse event was localized injection site reactions, with the majority graded mild to moderate in severity. They were generally the size of a quarter to half-dollar, and typically presented within the first few injections, after which they declined in incidence. In the trial, a case of vulvar cancer was determined to be potentially drug related, the company said.

Acelyrin is currently conducting a phase 2b/3 trial in PsA evaluating a range of doses, including significantly higher doses than in the phase 2 trial, that the company said “could potentially result in better ACR, PASI, and enthesitis resolution responses.”

The drug has been tested at doses up to 160 mg, in some cases for up to 3 years, in more than 400 patients with psoriasis, spondyloarthritis, noninfective uveitis, and hidradenitis suppurativa.

The full 46-week data from this trial will be presented at a future scientific meeting, according to the company.

The investigational interleukin-17A inhibitor izokibep showed higher response rates across a number of symptoms in adults with psoriatic arthritis (PsA) in an extension of its phase 2 trial out to 46 weeks, according to an announcement reporting some of the long-term data by the drug’s developer, Acelyrin.

Izokibep is an antibody mimetic designed to inhibit IL-17A that the company says has “high potency and the potential for robust tissue penetration due to its small molecular size, about one-tenth the size of a monoclonal antibody.”

“Patients want both rapid and meaningful improvement of their symptoms, as well as lasting – and ideally improving – resolution of disease over time. Building on the 16-week data for izokibep reported at EULAR and ACR [American College of Rheumatology] last year, the 46-week data now show not only continued but marked improvements over time in key areas of psoriatic arthritis including joint pain, skin psoriasis, and enthesitis,” Philip J. Mease, MD, director of rheumatology research at the Swedish Medical Center and clinical professor at the University of Washington, both in Seattle, and an investigator in the izokibep PsA program, said in the announcement.

The phase 2 trial tested two doses of izokibep – 40 mg and 80 mg – given by subcutaneous injection every 2 weeks – against placebo in 135 adult patients with active PsA. For inclusion in the trial, patients had to have at least three swollen and at least three tender joints and an inadequate response to prior therapy including NSAIDs, conventional synthetic disease-modifying antirheumatic drugs, or tumor necrosis factor inhibitors. At week 16, the placebo group transitioned to 80 mg izokibep every 2 weeks and the trial treatment period continued for up to 46 weeks.

The trial’s primary endpoint of a 50% or higher level of improvement in ACR response criteria (ACR 50) was achieved by 48% of those on the 40 mg dose at week 16 and by 50% at week 46. For the 80-mg group, this rate rose from 52% to 79%. In the group that went from placebo to 80 mg, the ACR 50 rose from 13% with placebo to 73% with izokibep at week 46.

Resolution of enthesitis, measured by the Leeds Enthesitis Index, among those on the 40 mg dose, was achieved by 63% at week 16 and 83% at week 46, and among those on the 80 mg dose, 88% at week 16 and 89% at week 46. Those on placebo who switched to 80 mg of izokibep at week 16 had an 80% rate of enthesitis resolution at week 46.

Total resolution of skin involvement – 100% clearance of psoriasis based on the Psoriasis Area Severity Index (PASI) – was observed at 46 weeks in 50% of those on 40 mg, 71% of those on 80 mg, and 67% of those on 80 mg after week 16.

In its announcement, Acelyrin did not report withdrawal rates from the study after 16 weeks and through 46 weeks, although the statement said that izokibep “was generally well tolerated through 46 weeks, which is in line with previous trials of izokibep.” The most common adverse event was localized injection site reactions, with the majority graded mild to moderate in severity. They were generally the size of a quarter to half-dollar, and typically presented within the first few injections, after which they declined in incidence. In the trial, a case of vulvar cancer was determined to be potentially drug related, the company said.

Acelyrin is currently conducting a phase 2b/3 trial in PsA evaluating a range of doses, including significantly higher doses than in the phase 2 trial, that the company said “could potentially result in better ACR, PASI, and enthesitis resolution responses.”

The drug has been tested at doses up to 160 mg, in some cases for up to 3 years, in more than 400 patients with psoriasis, spondyloarthritis, noninfective uveitis, and hidradenitis suppurativa.

The full 46-week data from this trial will be presented at a future scientific meeting, according to the company.

The investigational interleukin-17A inhibitor izokibep showed higher response rates across a number of symptoms in adults with psoriatic arthritis (PsA) in an extension of its phase 2 trial out to 46 weeks, according to an announcement reporting some of the long-term data by the drug’s developer, Acelyrin.

Izokibep is an antibody mimetic designed to inhibit IL-17A that the company says has “high potency and the potential for robust tissue penetration due to its small molecular size, about one-tenth the size of a monoclonal antibody.”

“Patients want both rapid and meaningful improvement of their symptoms, as well as lasting – and ideally improving – resolution of disease over time. Building on the 16-week data for izokibep reported at EULAR and ACR [American College of Rheumatology] last year, the 46-week data now show not only continued but marked improvements over time in key areas of psoriatic arthritis including joint pain, skin psoriasis, and enthesitis,” Philip J. Mease, MD, director of rheumatology research at the Swedish Medical Center and clinical professor at the University of Washington, both in Seattle, and an investigator in the izokibep PsA program, said in the announcement.

The phase 2 trial tested two doses of izokibep – 40 mg and 80 mg – given by subcutaneous injection every 2 weeks – against placebo in 135 adult patients with active PsA. For inclusion in the trial, patients had to have at least three swollen and at least three tender joints and an inadequate response to prior therapy including NSAIDs, conventional synthetic disease-modifying antirheumatic drugs, or tumor necrosis factor inhibitors. At week 16, the placebo group transitioned to 80 mg izokibep every 2 weeks and the trial treatment period continued for up to 46 weeks.

The trial’s primary endpoint of a 50% or higher level of improvement in ACR response criteria (ACR 50) was achieved by 48% of those on the 40 mg dose at week 16 and by 50% at week 46. For the 80-mg group, this rate rose from 52% to 79%. In the group that went from placebo to 80 mg, the ACR 50 rose from 13% with placebo to 73% with izokibep at week 46.

Resolution of enthesitis, measured by the Leeds Enthesitis Index, among those on the 40 mg dose, was achieved by 63% at week 16 and 83% at week 46, and among those on the 80 mg dose, 88% at week 16 and 89% at week 46. Those on placebo who switched to 80 mg of izokibep at week 16 had an 80% rate of enthesitis resolution at week 46.

Total resolution of skin involvement – 100% clearance of psoriasis based on the Psoriasis Area Severity Index (PASI) – was observed at 46 weeks in 50% of those on 40 mg, 71% of those on 80 mg, and 67% of those on 80 mg after week 16.

In its announcement, Acelyrin did not report withdrawal rates from the study after 16 weeks and through 46 weeks, although the statement said that izokibep “was generally well tolerated through 46 weeks, which is in line with previous trials of izokibep.” The most common adverse event was localized injection site reactions, with the majority graded mild to moderate in severity. They were generally the size of a quarter to half-dollar, and typically presented within the first few injections, after which they declined in incidence. In the trial, a case of vulvar cancer was determined to be potentially drug related, the company said.

Acelyrin is currently conducting a phase 2b/3 trial in PsA evaluating a range of doses, including significantly higher doses than in the phase 2 trial, that the company said “could potentially result in better ACR, PASI, and enthesitis resolution responses.”

The drug has been tested at doses up to 160 mg, in some cases for up to 3 years, in more than 400 patients with psoriasis, spondyloarthritis, noninfective uveitis, and hidradenitis suppurativa.

The full 46-week data from this trial will be presented at a future scientific meeting, according to the company.