MDedge Rheumatology

The Food and Drug Administration has approved an expanded indication for abatacept (Orencia) for treatment of psoriatic arthritis (PsA) in pediatric patients aged 2 years and older.

Juvenile psoriatic arthritis (JPsA) is a form of juvenile idiopathic arthritis (JIA). It is a rare condition, and it is estimated that as many as 5% of children with JIA have JPsA.

Olivier Le Moal/Getty Images

“The FDA’s approval of expanding Orencia’s indication adds a much-needed treatment option for children with JPsA, a rare, potentially serious condition characterized by chronic inflammation and joint damage,” said Carlos Dortrait, senior vice president of U.S. immunology at Bristol-Myers Squibb in a statement. BMS is the manufacturer of abatacept.

Abatacept was first approved in 2005 for the treatment of moderate to severe rheumatoid arthritis and was approved for treating active PsA in adults in 2017. In 2008, the drug was the first intravenous biologic approved for patients 6 years old and older to treat moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA). In 2017, a subcutaneous administration option was approved for children 2 years old and older with pJIA, according to a BMS press release.

This expanded approval was based on controlled studies of abatacept in adults with PsA; pharmacokinetic data from adults with RA, adults with PsA, and children with pJIA; and safety data from clinical studies in patients aged 2-17 years with pJIA.

“Children living with psoriatic arthritis can experience a number of challenging symptoms including swollen and painful joints,” Steven Taylor, president and CEO of the Arthritis Foundation, said in a BMS statement. “The FDA’s approval of Orencia for JPsA in patients 2 years of age and older means another treatment option is available to manage this rare chronic disease, which is exciting news for the arthritis community of young patients, their caregivers, and health care professionals.”

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

The Food and Drug Administration has approved an expanded indication for abatacept (Orencia) for treatment of psoriatic arthritis (PsA) in pediatric patients aged 2 years and older.

Juvenile psoriatic arthritis (JPsA) is a form of juvenile idiopathic arthritis (JIA). It is a rare condition, and it is estimated that as many as 5% of children with JIA have JPsA.

Olivier Le Moal/Getty Images

“The FDA’s approval of expanding Orencia’s indication adds a much-needed treatment option for children with JPsA, a rare, potentially serious condition characterized by chronic inflammation and joint damage,” said Carlos Dortrait, senior vice president of U.S. immunology at Bristol-Myers Squibb in a statement. BMS is the manufacturer of abatacept.

Abatacept was first approved in 2005 for the treatment of moderate to severe rheumatoid arthritis and was approved for treating active PsA in adults in 2017. In 2008, the drug was the first intravenous biologic approved for patients 6 years old and older to treat moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA). In 2017, a subcutaneous administration option was approved for children 2 years old and older with pJIA, according to a BMS press release.

This expanded approval was based on controlled studies of abatacept in adults with PsA; pharmacokinetic data from adults with RA, adults with PsA, and children with pJIA; and safety data from clinical studies in patients aged 2-17 years with pJIA.

“Children living with psoriatic arthritis can experience a number of challenging symptoms including swollen and painful joints,” Steven Taylor, president and CEO of the Arthritis Foundation, said in a BMS statement. “The FDA’s approval of Orencia for JPsA in patients 2 years of age and older means another treatment option is available to manage this rare chronic disease, which is exciting news for the arthritis community of young patients, their caregivers, and health care professionals.”

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

The Food and Drug Administration has approved an expanded indication for abatacept (Orencia) for treatment of psoriatic arthritis (PsA) in pediatric patients aged 2 years and older.

Juvenile psoriatic arthritis (JPsA) is a form of juvenile idiopathic arthritis (JIA). It is a rare condition, and it is estimated that as many as 5% of children with JIA have JPsA.

Olivier Le Moal/Getty Images

“The FDA’s approval of expanding Orencia’s indication adds a much-needed treatment option for children with JPsA, a rare, potentially serious condition characterized by chronic inflammation and joint damage,” said Carlos Dortrait, senior vice president of U.S. immunology at Bristol-Myers Squibb in a statement. BMS is the manufacturer of abatacept.

Abatacept was first approved in 2005 for the treatment of moderate to severe rheumatoid arthritis and was approved for treating active PsA in adults in 2017. In 2008, the drug was the first intravenous biologic approved for patients 6 years old and older to treat moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA). In 2017, a subcutaneous administration option was approved for children 2 years old and older with pJIA, according to a BMS press release.

This expanded approval was based on controlled studies of abatacept in adults with PsA; pharmacokinetic data from adults with RA, adults with PsA, and children with pJIA; and safety data from clinical studies in patients aged 2-17 years with pJIA.

“Children living with psoriatic arthritis can experience a number of challenging symptoms including swollen and painful joints,” Steven Taylor, president and CEO of the Arthritis Foundation, said in a BMS statement. “The FDA’s approval of Orencia for JPsA in patients 2 years of age and older means another treatment option is available to manage this rare chronic disease, which is exciting news for the arthritis community of young patients, their caregivers, and health care professionals.”

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

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Researchers have yet to crack how to analyze synovial tissue biopsy specimens to predict treatment responses for patients with rheumatoid arthritis.

According to new research, classifying patients by synovial fluid B-cell status was not reliable in predicting treatment response to etanercept, tocilizumab, or rituximab. More comprehensive molecular analyses may hold promise in developing models to predict treatment of a disease as heterogeneous as RA, wrote the authors, led by chief investigator Costantino Pitzalis, MD, head of the Centre for Experimental Medicine and Rheumatology at Queen Mary University of London.

The article was published in the November 2023 issue of The Lancet Rheumatology..
 

Trial-and-error treatment

Because clinicians do not have a way to reliably predict how patients may respond to certain medications, the current RA treatments involve trial and error.

Courtesy Dr. Arthur Mandelin, Northwestern University

“Both with regard to the first conventional synthetic disease-modifying antirheumatic drug (DMARD) for all patients and the first biologic DMARD for the subgroup of patients requiring these drugs, the choice of a drug is based on pragmatic arguments rather than on individual patient characteristics,” Annette H. van der Helm-van Mil, MD, PhD, professor of rheumatology at the Leiden University Medical Center, the Netherlands, wrote in an accompanying editorial.

Most research on predicting treatment response has used clinical features and blood biomarkers, but neither approach is reliably predictive. “Precision medicine, therefore, remains elusive,” she said. Newer research has focused on synovial tissue biopsy to inform research decisions.
 

The STRAP studies

In this newest study, researchers combined data from two clinical studies with identical design: the Stratification of Biological Therapies by Pathobiology in Biologic-Naive Patients With Rheumatoid Arthritis (STRAP) trial, taking place in the United Kingdom, and STRAP-EU, which recruited patients from the European Union. The trials are the largest biopsy-driven trials to date, according to the researchers.

In total, researchers recruited 223 biologic-naive adult patients from 26 universities in the United Kingdom and Europe. Participants underwent ultrasound-guided synovial tissue biopsy and were then randomly assigned to receive etanercept (72 patients), tocilizumab (73 patients), or rituximab (78 patients). In a histologic analysis, 121 patients were characterized as B-cell poor (BCP), 100 patients were classified as B-cell rich (BCR), and two patients were classified as undetermined.

“We hypothesized that patients with a low synovial histological or molecular B-cell score would have a lower response to rituximab than to etanercept or tocilizumab,” the authors wrote.

However, among the BCP patients, there were no significant differences between responses to treatment at week 16 in the rituximab group compared with the etanercept and tocilizumab groups put together. In both groups, around 60% of patients achieved the primary endpoint of at least 20% improvement in American College of Rheumatology response criteria.

The results suggest that “a dichotomic classification into synovial B cell poor versus rich is unable to predict treatment response in patients treated with rituximab compared with etanercept or tocilizumab,” the authors wrote.

The findings echo work from the same group of researchers in 2021. This study – the R4RA trial – enrolled 164 patients who previously had an inadequate response to tumor necrosis factor blockers. Researchers then used a similar histologic approach to compare patients’ responses to tocilizumab or rituximab.

Among patients classified as BCP, there was not a significant difference in treatment response between the tocilizumab group and the rituximab group. However, classifying patients as BCP with RNA sequencing did make a difference. In this subgroup, patients given tocilizumab demonstrated a significantly higher response rate than those treated with rituximab.
 

Molecular-level analyses needed

This 2021 study showed – and this most recent study further confirmed – that “histology is not the way to understand what’s going on with or be predictive with tissue,” said Harris R. Perlman, PhD, chief of rheumatology at Northwestern University in Chicago. He was not involved with the research.

Dr. Perlman

“Most people now believe that you really have to understand the tissue on a single-cell basis – using the gene expression of each individual cell – to really give you an idea of what’s happening in tissue,” he noted.

“RA continues to tell us that it is more complex than just something dichotomous,” added Elena Myasoedova, MD, PhD, director of the Inflammatory Arthritis Subspecialty Group at the Mayo Clinic in Rochester, Minn. She was not involved with the work.

Dr. Myasoedova

“Understanding more about the heterogeneity using different ‘-omics’ approaches and introducing a two- or three-dimensional approach with spatial biology can be helpful,” she said.

Spatial transcriptomics, for example, allows scientists to measure all gene activity in a tissue sample and to map where that gene activity is occurring.

“It helps us to understand and visualize molecules and their unique context within individual cells and tissues,” Dr. Myasoedova explained.

With advanced molecular analyses already available, Dr. Perlman is adamant that synovial tissue remains the key to unlocking precision medicine.

“The tissue is the golden ticket,” he said, “but it’s how you analyze it.”

And it’s clear that older analytic methods – such as histology – are not enough, he said.

A larger study of a size similar to that of STRAP that incorporates multiple sources of patient information, from gene expression to clinical symptoms, to create a predictive model would be key to understanding how to move the field of precision treatment for RA forward, he added.

“Precision medicine for RA is close,” he said. “We still have to get the numbers.”

The STRAP and STRAP-EU trials were jointly funded by the UK Medical Research Council and Versus Arthritis. Pfizer and Roche donated the study drugs through an investigator-sponsored research grant. Many authors, including Dr. Pitzalis, have multiple financial relationships with pharmaceutical companies. Dr. Van der Helm-van Mil and Dr. Myasoedova have disclosed no relevant financial relationships. Dr. Perlman consults for AbbVie, AnaptysBio, Exagen, Janssen, and Kiniksa.
 

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

Researchers have yet to crack how to analyze synovial tissue biopsy specimens to predict treatment responses for patients with rheumatoid arthritis.

According to new research, classifying patients by synovial fluid B-cell status was not reliable in predicting treatment response to etanercept, tocilizumab, or rituximab. More comprehensive molecular analyses may hold promise in developing models to predict treatment of a disease as heterogeneous as RA, wrote the authors, led by chief investigator Costantino Pitzalis, MD, head of the Centre for Experimental Medicine and Rheumatology at Queen Mary University of London.

The article was published in the November 2023 issue of The Lancet Rheumatology..
 

Trial-and-error treatment

Because clinicians do not have a way to reliably predict how patients may respond to certain medications, the current RA treatments involve trial and error.

Courtesy Dr. Arthur Mandelin, Northwestern University

“Both with regard to the first conventional synthetic disease-modifying antirheumatic drug (DMARD) for all patients and the first biologic DMARD for the subgroup of patients requiring these drugs, the choice of a drug is based on pragmatic arguments rather than on individual patient characteristics,” Annette H. van der Helm-van Mil, MD, PhD, professor of rheumatology at the Leiden University Medical Center, the Netherlands, wrote in an accompanying editorial.

Most research on predicting treatment response has used clinical features and blood biomarkers, but neither approach is reliably predictive. “Precision medicine, therefore, remains elusive,” she said. Newer research has focused on synovial tissue biopsy to inform research decisions.
 

The STRAP studies

In this newest study, researchers combined data from two clinical studies with identical design: the Stratification of Biological Therapies by Pathobiology in Biologic-Naive Patients With Rheumatoid Arthritis (STRAP) trial, taking place in the United Kingdom, and STRAP-EU, which recruited patients from the European Union. The trials are the largest biopsy-driven trials to date, according to the researchers.

In total, researchers recruited 223 biologic-naive adult patients from 26 universities in the United Kingdom and Europe. Participants underwent ultrasound-guided synovial tissue biopsy and were then randomly assigned to receive etanercept (72 patients), tocilizumab (73 patients), or rituximab (78 patients). In a histologic analysis, 121 patients were characterized as B-cell poor (BCP), 100 patients were classified as B-cell rich (BCR), and two patients were classified as undetermined.

“We hypothesized that patients with a low synovial histological or molecular B-cell score would have a lower response to rituximab than to etanercept or tocilizumab,” the authors wrote.

However, among the BCP patients, there were no significant differences between responses to treatment at week 16 in the rituximab group compared with the etanercept and tocilizumab groups put together. In both groups, around 60% of patients achieved the primary endpoint of at least 20% improvement in American College of Rheumatology response criteria.

The results suggest that “a dichotomic classification into synovial B cell poor versus rich is unable to predict treatment response in patients treated with rituximab compared with etanercept or tocilizumab,” the authors wrote.

The findings echo work from the same group of researchers in 2021. This study – the R4RA trial – enrolled 164 patients who previously had an inadequate response to tumor necrosis factor blockers. Researchers then used a similar histologic approach to compare patients’ responses to tocilizumab or rituximab.

Among patients classified as BCP, there was not a significant difference in treatment response between the tocilizumab group and the rituximab group. However, classifying patients as BCP with RNA sequencing did make a difference. In this subgroup, patients given tocilizumab demonstrated a significantly higher response rate than those treated with rituximab.
 

Molecular-level analyses needed

This 2021 study showed – and this most recent study further confirmed – that “histology is not the way to understand what’s going on with or be predictive with tissue,” said Harris R. Perlman, PhD, chief of rheumatology at Northwestern University in Chicago. He was not involved with the research.

Dr. Perlman

“Most people now believe that you really have to understand the tissue on a single-cell basis – using the gene expression of each individual cell – to really give you an idea of what’s happening in tissue,” he noted.

“RA continues to tell us that it is more complex than just something dichotomous,” added Elena Myasoedova, MD, PhD, director of the Inflammatory Arthritis Subspecialty Group at the Mayo Clinic in Rochester, Minn. She was not involved with the work.

Dr. Myasoedova

“Understanding more about the heterogeneity using different ‘-omics’ approaches and introducing a two- or three-dimensional approach with spatial biology can be helpful,” she said.

Spatial transcriptomics, for example, allows scientists to measure all gene activity in a tissue sample and to map where that gene activity is occurring.

“It helps us to understand and visualize molecules and their unique context within individual cells and tissues,” Dr. Myasoedova explained.

With advanced molecular analyses already available, Dr. Perlman is adamant that synovial tissue remains the key to unlocking precision medicine.

“The tissue is the golden ticket,” he said, “but it’s how you analyze it.”

And it’s clear that older analytic methods – such as histology – are not enough, he said.

A larger study of a size similar to that of STRAP that incorporates multiple sources of patient information, from gene expression to clinical symptoms, to create a predictive model would be key to understanding how to move the field of precision treatment for RA forward, he added.

“Precision medicine for RA is close,” he said. “We still have to get the numbers.”

The STRAP and STRAP-EU trials were jointly funded by the UK Medical Research Council and Versus Arthritis. Pfizer and Roche donated the study drugs through an investigator-sponsored research grant. Many authors, including Dr. Pitzalis, have multiple financial relationships with pharmaceutical companies. Dr. Van der Helm-van Mil and Dr. Myasoedova have disclosed no relevant financial relationships. Dr. Perlman consults for AbbVie, AnaptysBio, Exagen, Janssen, and Kiniksa.
 

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

Researchers have yet to crack how to analyze synovial tissue biopsy specimens to predict treatment responses for patients with rheumatoid arthritis.

According to new research, classifying patients by synovial fluid B-cell status was not reliable in predicting treatment response to etanercept, tocilizumab, or rituximab. More comprehensive molecular analyses may hold promise in developing models to predict treatment of a disease as heterogeneous as RA, wrote the authors, led by chief investigator Costantino Pitzalis, MD, head of the Centre for Experimental Medicine and Rheumatology at Queen Mary University of London.

The article was published in the November 2023 issue of The Lancet Rheumatology..
 

Trial-and-error treatment

Because clinicians do not have a way to reliably predict how patients may respond to certain medications, the current RA treatments involve trial and error.

Courtesy Dr. Arthur Mandelin, Northwestern University

“Both with regard to the first conventional synthetic disease-modifying antirheumatic drug (DMARD) for all patients and the first biologic DMARD for the subgroup of patients requiring these drugs, the choice of a drug is based on pragmatic arguments rather than on individual patient characteristics,” Annette H. van der Helm-van Mil, MD, PhD, professor of rheumatology at the Leiden University Medical Center, the Netherlands, wrote in an accompanying editorial.

Most research on predicting treatment response has used clinical features and blood biomarkers, but neither approach is reliably predictive. “Precision medicine, therefore, remains elusive,” she said. Newer research has focused on synovial tissue biopsy to inform research decisions.
 

The STRAP studies

In this newest study, researchers combined data from two clinical studies with identical design: the Stratification of Biological Therapies by Pathobiology in Biologic-Naive Patients With Rheumatoid Arthritis (STRAP) trial, taking place in the United Kingdom, and STRAP-EU, which recruited patients from the European Union. The trials are the largest biopsy-driven trials to date, according to the researchers.

In total, researchers recruited 223 biologic-naive adult patients from 26 universities in the United Kingdom and Europe. Participants underwent ultrasound-guided synovial tissue biopsy and were then randomly assigned to receive etanercept (72 patients), tocilizumab (73 patients), or rituximab (78 patients). In a histologic analysis, 121 patients were characterized as B-cell poor (BCP), 100 patients were classified as B-cell rich (BCR), and two patients were classified as undetermined.

“We hypothesized that patients with a low synovial histological or molecular B-cell score would have a lower response to rituximab than to etanercept or tocilizumab,” the authors wrote.

However, among the BCP patients, there were no significant differences between responses to treatment at week 16 in the rituximab group compared with the etanercept and tocilizumab groups put together. In both groups, around 60% of patients achieved the primary endpoint of at least 20% improvement in American College of Rheumatology response criteria.

The results suggest that “a dichotomic classification into synovial B cell poor versus rich is unable to predict treatment response in patients treated with rituximab compared with etanercept or tocilizumab,” the authors wrote.

The findings echo work from the same group of researchers in 2021. This study – the R4RA trial – enrolled 164 patients who previously had an inadequate response to tumor necrosis factor blockers. Researchers then used a similar histologic approach to compare patients’ responses to tocilizumab or rituximab.

Among patients classified as BCP, there was not a significant difference in treatment response between the tocilizumab group and the rituximab group. However, classifying patients as BCP with RNA sequencing did make a difference. In this subgroup, patients given tocilizumab demonstrated a significantly higher response rate than those treated with rituximab.
 

Molecular-level analyses needed

This 2021 study showed – and this most recent study further confirmed – that “histology is not the way to understand what’s going on with or be predictive with tissue,” said Harris R. Perlman, PhD, chief of rheumatology at Northwestern University in Chicago. He was not involved with the research.

Dr. Perlman

“Most people now believe that you really have to understand the tissue on a single-cell basis – using the gene expression of each individual cell – to really give you an idea of what’s happening in tissue,” he noted.

“RA continues to tell us that it is more complex than just something dichotomous,” added Elena Myasoedova, MD, PhD, director of the Inflammatory Arthritis Subspecialty Group at the Mayo Clinic in Rochester, Minn. She was not involved with the work.

Dr. Myasoedova

“Understanding more about the heterogeneity using different ‘-omics’ approaches and introducing a two- or three-dimensional approach with spatial biology can be helpful,” she said.

Spatial transcriptomics, for example, allows scientists to measure all gene activity in a tissue sample and to map where that gene activity is occurring.

“It helps us to understand and visualize molecules and their unique context within individual cells and tissues,” Dr. Myasoedova explained.

With advanced molecular analyses already available, Dr. Perlman is adamant that synovial tissue remains the key to unlocking precision medicine.

“The tissue is the golden ticket,” he said, “but it’s how you analyze it.”

And it’s clear that older analytic methods – such as histology – are not enough, he said.

A larger study of a size similar to that of STRAP that incorporates multiple sources of patient information, from gene expression to clinical symptoms, to create a predictive model would be key to understanding how to move the field of precision treatment for RA forward, he added.

“Precision medicine for RA is close,” he said. “We still have to get the numbers.”

The STRAP and STRAP-EU trials were jointly funded by the UK Medical Research Council and Versus Arthritis. Pfizer and Roche donated the study drugs through an investigator-sponsored research grant. Many authors, including Dr. Pitzalis, have multiple financial relationships with pharmaceutical companies. Dr. Van der Helm-van Mil and Dr. Myasoedova have disclosed no relevant financial relationships. Dr. Perlman consults for AbbVie, AnaptysBio, Exagen, Janssen, and Kiniksa.
 

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

Patients with hand osteoarthritis (OA) and MRI-detected synovitis who took methotrexate (MTX) 20 mg weekly over a 6-month period had a significant and potentially clinically meaningful reduction in pain and stiffness over those who received placebo in the first randomized controlled trial of its kind to show positive results with the drug.

Patients who were randomly assigned to MTX took 10 mg orally for the first 4 weeks then increased to 20 mg for the rest of the trial, with differences in the primary outcome of pain measured by visual analog scale (VAS) first becoming significant over placebo at 3 months.

Senior author of the METHODS study (Methotrexate to Treat Hand Osteoarthritis with Synovitis), Flavia Cicuttini, PhD, MSc, head of the musculoskeletal unit at Monash University and head of rheumatology at Alfred Hospital, Melbourne, Australia, noted that the effect of MTX was higher than effect sizes that have been reported for NSAIDs on pain in hip or knee OA.

Astrid Gast/Thinkstock

The study was published online October 12 in The Lancet.

METHODS makes improvements on past studies

While OA is traditionally categorized as a noninflammatory process, it’s known that there are some patients who have a clinical phenotype characterized by joint swelling (synovitis) and others develop erosive disease. MTX is one of the most common therapies for inflammatory arthritis and standard of care for rheumatoid arthritis (RA) management. Previous studies of methotrexate showed lack of efficacy in hand OA but may have been because of the use of a low dose, poor power due to moderate sample size, and failure to target the specific inflammatory OA phenotype.

Dr. Cicuttini

In an interview, Dr. Cicuttini noted the selection of methotrexate for this trial was intentional. “We considered the evidence and decided to test methotrexate because we know it is effective in inflammatory arthritis, and its mode of action is broader than the more selective anti-TNF [tumor necrosis factor] agents,” which she noted have failed in prior hand OA trials. She also noted that the only previous randomized controlled trial of MTX tested a dose of 10 mg/week, rather than the 20 mg/week dose used in METHODS. 
 

Study details and results

METHODS was a randomized, double-blind, placebo-controlled trial at multiple sites within Australia. Patients were recruited from 2017 to 2022, with a temporary pause in 2020 during the COVID-19 pandemic because of safety concerns regarding MTX use. Participants included in this study were aged 40-75 years, had pain in hand joints for most days in the past 3 months, and a pain score of at least 40 mm on a 100-mm VAS in the past 7 days.

The participants’ hand OA fulfilled American College of Rheumatology criteria, radiographic osteoarthritis (Kellgren and Lawrence grade 2 or more) in at least one joint, and MRI-detected synovitis of grade 1 or more in at least one joint. They excluded patients with concomitant rheumatic disease, gout, psoriasis, positive rheumatoid factor or anti-cyclic citrullinated peptides, or elevated inflammatory markers (erythrocyte sedimentation rate or C-reactive protein), as well as those with contraindication to methotrexate or MRI.

The trials’ 97 participants were assigned 1:1 to MTX or placebo using block randomization. The MTX group started on oral MTX 10 mg weekly for the first 4 weeks, followed by 20 mg weekly for the remainder of the study. Participants took folic acid 5 mg once a day to reduce risk of MTX-related side effects.

The mean age of the participants was 61 years, with 70% female. Baseline characteristics were generally well-balanced, except for higher mean BMI in the MTX group. At 6 months, the MTX group had a greater reduction in mean VAS pain than the placebo group (–15.2 mm vs. –7.7 mm; adjusted between-group difference, –9.9 mm). The minimally clinically important difference for OA trials is a 15-mm change (out of 100) in VAS pain.

The MTX group also had greater reduction in mean Australian Canadian OA Hand Index (AUSCAN) score for pain and stiffness at 6 months, compared with placebo, but there were no differences in other secondary outcomes (mean AUSCAN, Functional Index for Hand Osteoarthritis, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, or grip strength).

MTX was well-tolerated with no serious adverse events related to treatment; only 5 of 50 participants in the MTX group and 4 of 47 in the placebo group discontinued study medication. Incidence of adverse events was similar in the two groups throughout the trial, including mild leukopenia, elevated liver enzymes, mild reduction of hemoglobin, and raised creatinine. None of the laboratory abnormalities required change in medication dosage or affected ability to continue in the study. 
 

Qualifications and considerations for MTX use

Commenting on the study, OA researcher Amanda E. Nelson, MD, MSCR, associate professor of medicine at the University of North Carolina at Chapel Hill’s Thurston Arthritis Research Center, said that its overall design was “excellent,” including appropriate masking, controls, randomization, and power and sample size calculations, contributing to “the trial’s relatively positive, although still modest, results.” Dr. Nelson was not involved with the METHODS study.

Dr. Nelson

Several factors may have contributed to the study’s success, including the broader mechanism of action of methotrexate and higher dose used, Ida K. Haugen, MD, PhD, senior researcher at Diakonhjemmet Hospital’s Center for Treatment of Rheumatic and Musculoskeletal Diseases in Oslo, Norway, told this news organization.

She noted that the MTX 20 mg/week dosage is similar to what is used in treatment of RA and may be key to better targeting inflammation.

Nicolas Tourrenc

“Furthermore, the study included individuals with hand OA and synovitis by MRI, and thus may have found the right patient population in comparison to prior studies,” Dr. Haugen said.

Dr. Cicuttini agreed, noting that “previous trials [of MTX] did not target the inflammatory phenotype of hand osteoarthritis that would be expected to respond.” In the previous randomized controlled trial of MTX in hand OA, only 29 of a total 1024 joints had synovitis, she explained. “Their inclusion criteria were individuals with severe erosive hand osteoarthritis, suggesting that this later-stage disease is less likely to respond.”

Dr. Cicuttini said that she saw no specific issues in regard to potential use of MTX in the OA population in the clinic. “The data we have, together with the large experience we have with using methotrexate and the fact that treatments for hand OA are not very effective, means that it would be reasonable to offer this to patients with hand OA and inflammation,” she said. “The level of evidence for an effect of methotrexate would need to be discussed with the patient. The discussion around the use of methotrexate would then need to proceed in the same way we discuss the use of methotrexate with patients when used for other inflammatory joint diseases, and the decision is then made with the patient.”

In contrast, Dr. Nelson expressed some concerns regarding the immediate use of MTX for this population. “Many individuals with hand OA have multiple medical comorbidities and polypharmacy, which are important when considering additional treatments, particularly those with modest benefit and potential adverse effects over the long term,” she said. “I do not think this single study provides enough evidence to suggest that all such patients should be treated with methotrexate, and more data, particularly about long-term use and optimal risk stratification, is needed.” 

While MTX use in refractory inflammatory hand OA is not yet recommended in international guidelines, Dr. Haugen believes this study supports use of MTX in this patient population. Given that MRI and ultrasound may not always be available to identify synovitis, Dr. Nelson and Dr. Haugen suggested identifying patients who may benefit through careful history and clinical examination for evidence of swollen joints. In addition, Dr. Cicuttini explained that she would not necessarily use MTX in patients with erosive OA radiographically because it may be a later stage of disease that is less likely to respond.

The authors highlighted potential limitations of the METHODS trial. They initially planned to study whether MTX reduced pain and improved radiographic progression at 2 years, but since they paused the study for 7 months during the COVID-19 pandemic, they amended the trial protocol and focused on pain reduction at 6 months as the primary endpoint instead.

Tender and swollen joint counts were initially going to be included, but this was modified given the use of virtual telemedicine visits during the pandemic. Dr. Cicuttini said that further studies are underway to identify potential subpopulations who may benefit from immunosuppression, and others are needed to determine whether MTX reduces joint damage and slows disease progression in hand OA with inflammation.

Dr. Cicuttini said her research group is interested to see whether women who develop hand OA around the time of menopause (“menopausal OA”) are a group that could benefit. Dr. Haugen noted that she is involved in a study testing MTX in erosive hand OA (the MERINO trial). 

The study was funded by a project grant from the National Health and Medical Research Council of Australia. The authors reported no relevant financial relationships.
 

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

Patients with hand osteoarthritis (OA) and MRI-detected synovitis who took methotrexate (MTX) 20 mg weekly over a 6-month period had a significant and potentially clinically meaningful reduction in pain and stiffness over those who received placebo in the first randomized controlled trial of its kind to show positive results with the drug.

Patients who were randomly assigned to MTX took 10 mg orally for the first 4 weeks then increased to 20 mg for the rest of the trial, with differences in the primary outcome of pain measured by visual analog scale (VAS) first becoming significant over placebo at 3 months.

Senior author of the METHODS study (Methotrexate to Treat Hand Osteoarthritis with Synovitis), Flavia Cicuttini, PhD, MSc, head of the musculoskeletal unit at Monash University and head of rheumatology at Alfred Hospital, Melbourne, Australia, noted that the effect of MTX was higher than effect sizes that have been reported for NSAIDs on pain in hip or knee OA.

Astrid Gast/Thinkstock

The study was published online October 12 in The Lancet.

METHODS makes improvements on past studies

While OA is traditionally categorized as a noninflammatory process, it’s known that there are some patients who have a clinical phenotype characterized by joint swelling (synovitis) and others develop erosive disease. MTX is one of the most common therapies for inflammatory arthritis and standard of care for rheumatoid arthritis (RA) management. Previous studies of methotrexate showed lack of efficacy in hand OA but may have been because of the use of a low dose, poor power due to moderate sample size, and failure to target the specific inflammatory OA phenotype.

Dr. Cicuttini

In an interview, Dr. Cicuttini noted the selection of methotrexate for this trial was intentional. “We considered the evidence and decided to test methotrexate because we know it is effective in inflammatory arthritis, and its mode of action is broader than the more selective anti-TNF [tumor necrosis factor] agents,” which she noted have failed in prior hand OA trials. She also noted that the only previous randomized controlled trial of MTX tested a dose of 10 mg/week, rather than the 20 mg/week dose used in METHODS. 
 

Study details and results

METHODS was a randomized, double-blind, placebo-controlled trial at multiple sites within Australia. Patients were recruited from 2017 to 2022, with a temporary pause in 2020 during the COVID-19 pandemic because of safety concerns regarding MTX use. Participants included in this study were aged 40-75 years, had pain in hand joints for most days in the past 3 months, and a pain score of at least 40 mm on a 100-mm VAS in the past 7 days.

The participants’ hand OA fulfilled American College of Rheumatology criteria, radiographic osteoarthritis (Kellgren and Lawrence grade 2 or more) in at least one joint, and MRI-detected synovitis of grade 1 or more in at least one joint. They excluded patients with concomitant rheumatic disease, gout, psoriasis, positive rheumatoid factor or anti-cyclic citrullinated peptides, or elevated inflammatory markers (erythrocyte sedimentation rate or C-reactive protein), as well as those with contraindication to methotrexate or MRI.

The trials’ 97 participants were assigned 1:1 to MTX or placebo using block randomization. The MTX group started on oral MTX 10 mg weekly for the first 4 weeks, followed by 20 mg weekly for the remainder of the study. Participants took folic acid 5 mg once a day to reduce risk of MTX-related side effects.

The mean age of the participants was 61 years, with 70% female. Baseline characteristics were generally well-balanced, except for higher mean BMI in the MTX group. At 6 months, the MTX group had a greater reduction in mean VAS pain than the placebo group (–15.2 mm vs. –7.7 mm; adjusted between-group difference, –9.9 mm). The minimally clinically important difference for OA trials is a 15-mm change (out of 100) in VAS pain.

The MTX group also had greater reduction in mean Australian Canadian OA Hand Index (AUSCAN) score for pain and stiffness at 6 months, compared with placebo, but there were no differences in other secondary outcomes (mean AUSCAN, Functional Index for Hand Osteoarthritis, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, or grip strength).

MTX was well-tolerated with no serious adverse events related to treatment; only 5 of 50 participants in the MTX group and 4 of 47 in the placebo group discontinued study medication. Incidence of adverse events was similar in the two groups throughout the trial, including mild leukopenia, elevated liver enzymes, mild reduction of hemoglobin, and raised creatinine. None of the laboratory abnormalities required change in medication dosage or affected ability to continue in the study. 
 

Qualifications and considerations for MTX use

Commenting on the study, OA researcher Amanda E. Nelson, MD, MSCR, associate professor of medicine at the University of North Carolina at Chapel Hill’s Thurston Arthritis Research Center, said that its overall design was “excellent,” including appropriate masking, controls, randomization, and power and sample size calculations, contributing to “the trial’s relatively positive, although still modest, results.” Dr. Nelson was not involved with the METHODS study.

Dr. Nelson

Several factors may have contributed to the study’s success, including the broader mechanism of action of methotrexate and higher dose used, Ida K. Haugen, MD, PhD, senior researcher at Diakonhjemmet Hospital’s Center for Treatment of Rheumatic and Musculoskeletal Diseases in Oslo, Norway, told this news organization.

She noted that the MTX 20 mg/week dosage is similar to what is used in treatment of RA and may be key to better targeting inflammation.

Nicolas Tourrenc

“Furthermore, the study included individuals with hand OA and synovitis by MRI, and thus may have found the right patient population in comparison to prior studies,” Dr. Haugen said.

Dr. Cicuttini agreed, noting that “previous trials [of MTX] did not target the inflammatory phenotype of hand osteoarthritis that would be expected to respond.” In the previous randomized controlled trial of MTX in hand OA, only 29 of a total 1024 joints had synovitis, she explained. “Their inclusion criteria were individuals with severe erosive hand osteoarthritis, suggesting that this later-stage disease is less likely to respond.”

Dr. Cicuttini said that she saw no specific issues in regard to potential use of MTX in the OA population in the clinic. “The data we have, together with the large experience we have with using methotrexate and the fact that treatments for hand OA are not very effective, means that it would be reasonable to offer this to patients with hand OA and inflammation,” she said. “The level of evidence for an effect of methotrexate would need to be discussed with the patient. The discussion around the use of methotrexate would then need to proceed in the same way we discuss the use of methotrexate with patients when used for other inflammatory joint diseases, and the decision is then made with the patient.”

In contrast, Dr. Nelson expressed some concerns regarding the immediate use of MTX for this population. “Many individuals with hand OA have multiple medical comorbidities and polypharmacy, which are important when considering additional treatments, particularly those with modest benefit and potential adverse effects over the long term,” she said. “I do not think this single study provides enough evidence to suggest that all such patients should be treated with methotrexate, and more data, particularly about long-term use and optimal risk stratification, is needed.” 

While MTX use in refractory inflammatory hand OA is not yet recommended in international guidelines, Dr. Haugen believes this study supports use of MTX in this patient population. Given that MRI and ultrasound may not always be available to identify synovitis, Dr. Nelson and Dr. Haugen suggested identifying patients who may benefit through careful history and clinical examination for evidence of swollen joints. In addition, Dr. Cicuttini explained that she would not necessarily use MTX in patients with erosive OA radiographically because it may be a later stage of disease that is less likely to respond.

The authors highlighted potential limitations of the METHODS trial. They initially planned to study whether MTX reduced pain and improved radiographic progression at 2 years, but since they paused the study for 7 months during the COVID-19 pandemic, they amended the trial protocol and focused on pain reduction at 6 months as the primary endpoint instead.

Tender and swollen joint counts were initially going to be included, but this was modified given the use of virtual telemedicine visits during the pandemic. Dr. Cicuttini said that further studies are underway to identify potential subpopulations who may benefit from immunosuppression, and others are needed to determine whether MTX reduces joint damage and slows disease progression in hand OA with inflammation.

Dr. Cicuttini said her research group is interested to see whether women who develop hand OA around the time of menopause (“menopausal OA”) are a group that could benefit. Dr. Haugen noted that she is involved in a study testing MTX in erosive hand OA (the MERINO trial). 

The study was funded by a project grant from the National Health and Medical Research Council of Australia. The authors reported no relevant financial relationships.
 

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

Patients with hand osteoarthritis (OA) and MRI-detected synovitis who took methotrexate (MTX) 20 mg weekly over a 6-month period had a significant and potentially clinically meaningful reduction in pain and stiffness over those who received placebo in the first randomized controlled trial of its kind to show positive results with the drug.

Patients who were randomly assigned to MTX took 10 mg orally for the first 4 weeks then increased to 20 mg for the rest of the trial, with differences in the primary outcome of pain measured by visual analog scale (VAS) first becoming significant over placebo at 3 months.

Senior author of the METHODS study (Methotrexate to Treat Hand Osteoarthritis with Synovitis), Flavia Cicuttini, PhD, MSc, head of the musculoskeletal unit at Monash University and head of rheumatology at Alfred Hospital, Melbourne, Australia, noted that the effect of MTX was higher than effect sizes that have been reported for NSAIDs on pain in hip or knee OA.

Astrid Gast/Thinkstock

The study was published online October 12 in The Lancet.

METHODS makes improvements on past studies

While OA is traditionally categorized as a noninflammatory process, it’s known that there are some patients who have a clinical phenotype characterized by joint swelling (synovitis) and others develop erosive disease. MTX is one of the most common therapies for inflammatory arthritis and standard of care for rheumatoid arthritis (RA) management. Previous studies of methotrexate showed lack of efficacy in hand OA but may have been because of the use of a low dose, poor power due to moderate sample size, and failure to target the specific inflammatory OA phenotype.

Dr. Cicuttini

In an interview, Dr. Cicuttini noted the selection of methotrexate for this trial was intentional. “We considered the evidence and decided to test methotrexate because we know it is effective in inflammatory arthritis, and its mode of action is broader than the more selective anti-TNF [tumor necrosis factor] agents,” which she noted have failed in prior hand OA trials. She also noted that the only previous randomized controlled trial of MTX tested a dose of 10 mg/week, rather than the 20 mg/week dose used in METHODS. 
 

Study details and results

METHODS was a randomized, double-blind, placebo-controlled trial at multiple sites within Australia. Patients were recruited from 2017 to 2022, with a temporary pause in 2020 during the COVID-19 pandemic because of safety concerns regarding MTX use. Participants included in this study were aged 40-75 years, had pain in hand joints for most days in the past 3 months, and a pain score of at least 40 mm on a 100-mm VAS in the past 7 days.

The participants’ hand OA fulfilled American College of Rheumatology criteria, radiographic osteoarthritis (Kellgren and Lawrence grade 2 or more) in at least one joint, and MRI-detected synovitis of grade 1 or more in at least one joint. They excluded patients with concomitant rheumatic disease, gout, psoriasis, positive rheumatoid factor or anti-cyclic citrullinated peptides, or elevated inflammatory markers (erythrocyte sedimentation rate or C-reactive protein), as well as those with contraindication to methotrexate or MRI.

The trials’ 97 participants were assigned 1:1 to MTX or placebo using block randomization. The MTX group started on oral MTX 10 mg weekly for the first 4 weeks, followed by 20 mg weekly for the remainder of the study. Participants took folic acid 5 mg once a day to reduce risk of MTX-related side effects.

The mean age of the participants was 61 years, with 70% female. Baseline characteristics were generally well-balanced, except for higher mean BMI in the MTX group. At 6 months, the MTX group had a greater reduction in mean VAS pain than the placebo group (–15.2 mm vs. –7.7 mm; adjusted between-group difference, –9.9 mm). The minimally clinically important difference for OA trials is a 15-mm change (out of 100) in VAS pain.

The MTX group also had greater reduction in mean Australian Canadian OA Hand Index (AUSCAN) score for pain and stiffness at 6 months, compared with placebo, but there were no differences in other secondary outcomes (mean AUSCAN, Functional Index for Hand Osteoarthritis, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, or grip strength).

MTX was well-tolerated with no serious adverse events related to treatment; only 5 of 50 participants in the MTX group and 4 of 47 in the placebo group discontinued study medication. Incidence of adverse events was similar in the two groups throughout the trial, including mild leukopenia, elevated liver enzymes, mild reduction of hemoglobin, and raised creatinine. None of the laboratory abnormalities required change in medication dosage or affected ability to continue in the study. 
 

Qualifications and considerations for MTX use

Commenting on the study, OA researcher Amanda E. Nelson, MD, MSCR, associate professor of medicine at the University of North Carolina at Chapel Hill’s Thurston Arthritis Research Center, said that its overall design was “excellent,” including appropriate masking, controls, randomization, and power and sample size calculations, contributing to “the trial’s relatively positive, although still modest, results.” Dr. Nelson was not involved with the METHODS study.

Dr. Nelson

Several factors may have contributed to the study’s success, including the broader mechanism of action of methotrexate and higher dose used, Ida K. Haugen, MD, PhD, senior researcher at Diakonhjemmet Hospital’s Center for Treatment of Rheumatic and Musculoskeletal Diseases in Oslo, Norway, told this news organization.

She noted that the MTX 20 mg/week dosage is similar to what is used in treatment of RA and may be key to better targeting inflammation.

Nicolas Tourrenc

“Furthermore, the study included individuals with hand OA and synovitis by MRI, and thus may have found the right patient population in comparison to prior studies,” Dr. Haugen said.

Dr. Cicuttini agreed, noting that “previous trials [of MTX] did not target the inflammatory phenotype of hand osteoarthritis that would be expected to respond.” In the previous randomized controlled trial of MTX in hand OA, only 29 of a total 1024 joints had synovitis, she explained. “Their inclusion criteria were individuals with severe erosive hand osteoarthritis, suggesting that this later-stage disease is less likely to respond.”

Dr. Cicuttini said that she saw no specific issues in regard to potential use of MTX in the OA population in the clinic. “The data we have, together with the large experience we have with using methotrexate and the fact that treatments for hand OA are not very effective, means that it would be reasonable to offer this to patients with hand OA and inflammation,” she said. “The level of evidence for an effect of methotrexate would need to be discussed with the patient. The discussion around the use of methotrexate would then need to proceed in the same way we discuss the use of methotrexate with patients when used for other inflammatory joint diseases, and the decision is then made with the patient.”

In contrast, Dr. Nelson expressed some concerns regarding the immediate use of MTX for this population. “Many individuals with hand OA have multiple medical comorbidities and polypharmacy, which are important when considering additional treatments, particularly those with modest benefit and potential adverse effects over the long term,” she said. “I do not think this single study provides enough evidence to suggest that all such patients should be treated with methotrexate, and more data, particularly about long-term use and optimal risk stratification, is needed.” 

While MTX use in refractory inflammatory hand OA is not yet recommended in international guidelines, Dr. Haugen believes this study supports use of MTX in this patient population. Given that MRI and ultrasound may not always be available to identify synovitis, Dr. Nelson and Dr. Haugen suggested identifying patients who may benefit through careful history and clinical examination for evidence of swollen joints. In addition, Dr. Cicuttini explained that she would not necessarily use MTX in patients with erosive OA radiographically because it may be a later stage of disease that is less likely to respond.

The authors highlighted potential limitations of the METHODS trial. They initially planned to study whether MTX reduced pain and improved radiographic progression at 2 years, but since they paused the study for 7 months during the COVID-19 pandemic, they amended the trial protocol and focused on pain reduction at 6 months as the primary endpoint instead.

Tender and swollen joint counts were initially going to be included, but this was modified given the use of virtual telemedicine visits during the pandemic. Dr. Cicuttini said that further studies are underway to identify potential subpopulations who may benefit from immunosuppression, and others are needed to determine whether MTX reduces joint damage and slows disease progression in hand OA with inflammation.

Dr. Cicuttini said her research group is interested to see whether women who develop hand OA around the time of menopause (“menopausal OA”) are a group that could benefit. Dr. Haugen noted that she is involved in a study testing MTX in erosive hand OA (the MERINO trial). 

The study was funded by a project grant from the National Health and Medical Research Council of Australia. The authors reported no relevant financial relationships.
 

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

Key clinical point: Methotrexate remains the anchor untargeted conventional treatment for rheumatoid arthritis (RA); however, several alternatives are now available in case of suboptimal outcomes or unacceptable adverse events with methotrexate.

Major finding: Methotrexate reduced the imputed tender joint count (TJCi) by 5.18 joints (95% credible interval [CrI] 4.07-6.28 joints) compared with placebo. Cyclophosphamide fared better than methotrexate in terms of TJCi reduction (6.08 joints; 95% CrI 0.44-11.66 joints), but glucocorticoids (−2.54 joints; 95% CrI −5.16 to 0.08 joints) and the remaining drugs showed similar or lower reductions in the TJCi.

Study details: Findings are from a network meta-analysis of 29 interventions investigated in 132 randomized clinical trials including 13,260 patients with RA who were randomly assigned to receive conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids, placebo, or a pharmacologic non-disease-modifying comparator.

Disclosures: This study was funded by grants from the Danish Regions Medicine Fund and other sources. The authors declared no conflicts of interest.

Source: Guski LS et al. Monotreatment with conventional antirheumatic drugs or glucocorticoids in rheumatoid arthritis: A network meta-analysis. JAMA Netw Open. 2023;6(10):e2335950 (Oct 6). doi: 10.1001/jamanetworkopen.2023.35950

Key clinical point: Methotrexate remains the anchor untargeted conventional treatment for rheumatoid arthritis (RA); however, several alternatives are now available in case of suboptimal outcomes or unacceptable adverse events with methotrexate.

Major finding: Methotrexate reduced the imputed tender joint count (TJCi) by 5.18 joints (95% credible interval [CrI] 4.07-6.28 joints) compared with placebo. Cyclophosphamide fared better than methotrexate in terms of TJCi reduction (6.08 joints; 95% CrI 0.44-11.66 joints), but glucocorticoids (−2.54 joints; 95% CrI −5.16 to 0.08 joints) and the remaining drugs showed similar or lower reductions in the TJCi.

Study details: Findings are from a network meta-analysis of 29 interventions investigated in 132 randomized clinical trials including 13,260 patients with RA who were randomly assigned to receive conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids, placebo, or a pharmacologic non-disease-modifying comparator.

Disclosures: This study was funded by grants from the Danish Regions Medicine Fund and other sources. The authors declared no conflicts of interest.

Source: Guski LS et al. Monotreatment with conventional antirheumatic drugs or glucocorticoids in rheumatoid arthritis: A network meta-analysis. JAMA Netw Open. 2023;6(10):e2335950 (Oct 6). doi: 10.1001/jamanetworkopen.2023.35950

Key clinical point: Methotrexate remains the anchor untargeted conventional treatment for rheumatoid arthritis (RA); however, several alternatives are now available in case of suboptimal outcomes or unacceptable adverse events with methotrexate.

Major finding: Methotrexate reduced the imputed tender joint count (TJCi) by 5.18 joints (95% credible interval [CrI] 4.07-6.28 joints) compared with placebo. Cyclophosphamide fared better than methotrexate in terms of TJCi reduction (6.08 joints; 95% CrI 0.44-11.66 joints), but glucocorticoids (−2.54 joints; 95% CrI −5.16 to 0.08 joints) and the remaining drugs showed similar or lower reductions in the TJCi.

Study details: Findings are from a network meta-analysis of 29 interventions investigated in 132 randomized clinical trials including 13,260 patients with RA who were randomly assigned to receive conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids, placebo, or a pharmacologic non-disease-modifying comparator.

Disclosures: This study was funded by grants from the Danish Regions Medicine Fund and other sources. The authors declared no conflicts of interest.

Source: Guski LS et al. Monotreatment with conventional antirheumatic drugs or glucocorticoids in rheumatoid arthritis: A network meta-analysis. JAMA Netw Open. 2023;6(10):e2335950 (Oct 6). doi: 10.1001/jamanetworkopen.2023.35950

Key clinical point: The risk for cardiovascular events was similar with Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA), although the risk may be slightly higher in elderly patients.

Major finding: JAKi vs bDMARD were not associated with a significantly different risk for cardiovascular events (adjusted incidence rate ratio [aIRR] 1.01; P  =  .965), but with a trend for a higher cardiovascular risk among patients > 65 years old (aIRR 1.24; 95% CI 0.80-1.91) and a lower risk among patients < 65 years old (aIRR 0.70; 95% CI 0.39-1.28).

Study details: Findings are from a retrospective inception cohort study including 15,191 patients with RA from the IQVIA’s Real-World Data Longitudinal Prescription database who had started a new bDMARD or JAKi.

Disclosures: This study was supported by an unrestricted educational grant from Pfizer BV. Two authors declared receiving past grants to the institution from various sources, including Pfizer. The other authors declared no conflicts of interest.

Source: Popa CD et al. Therapy with JAK inhibitors or bDMARDs and the risk of cardiovascular events in the Dutch rheumatoid arthritis population. Rheumatology (Oxford). 2023 (Oct 5). doi: 10.1093/rheumatology/kead531

Key clinical point: The risk for cardiovascular events was similar with Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA), although the risk may be slightly higher in elderly patients.

Major finding: JAKi vs bDMARD were not associated with a significantly different risk for cardiovascular events (adjusted incidence rate ratio [aIRR] 1.01; P  =  .965), but with a trend for a higher cardiovascular risk among patients > 65 years old (aIRR 1.24; 95% CI 0.80-1.91) and a lower risk among patients < 65 years old (aIRR 0.70; 95% CI 0.39-1.28).

Study details: Findings are from a retrospective inception cohort study including 15,191 patients with RA from the IQVIA’s Real-World Data Longitudinal Prescription database who had started a new bDMARD or JAKi.

Disclosures: This study was supported by an unrestricted educational grant from Pfizer BV. Two authors declared receiving past grants to the institution from various sources, including Pfizer. The other authors declared no conflicts of interest.

Source: Popa CD et al. Therapy with JAK inhibitors or bDMARDs and the risk of cardiovascular events in the Dutch rheumatoid arthritis population. Rheumatology (Oxford). 2023 (Oct 5). doi: 10.1093/rheumatology/kead531

Key clinical point: The risk for cardiovascular events was similar with Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA), although the risk may be slightly higher in elderly patients.

Major finding: JAKi vs bDMARD were not associated with a significantly different risk for cardiovascular events (adjusted incidence rate ratio [aIRR] 1.01; P  =  .965), but with a trend for a higher cardiovascular risk among patients > 65 years old (aIRR 1.24; 95% CI 0.80-1.91) and a lower risk among patients < 65 years old (aIRR 0.70; 95% CI 0.39-1.28).

Study details: Findings are from a retrospective inception cohort study including 15,191 patients with RA from the IQVIA’s Real-World Data Longitudinal Prescription database who had started a new bDMARD or JAKi.

Disclosures: This study was supported by an unrestricted educational grant from Pfizer BV. Two authors declared receiving past grants to the institution from various sources, including Pfizer. The other authors declared no conflicts of interest.

Source: Popa CD et al. Therapy with JAK inhibitors or bDMARDs and the risk of cardiovascular events in the Dutch rheumatoid arthritis population. Rheumatology (Oxford). 2023 (Oct 5). doi: 10.1093/rheumatology/kead531

Key clinical point: Patients with difficult-to-treat (D2T) rheumatoid arthritis (RA) had a higher disease activity despite treatment with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) and demonstrated higher withdrawal rates due to inefficacy.

Major finding: Patients with vs without D2T RA had a higher Simplified Disease Activity Index (SDAI; P  =  .003) and higher withdrawal rates for b/tsDMARD due to inefficacy (P < .001). Higher SDAI (adjusted odds ratio [aOR] 1.06; P  =  .014), longer disease duration (aOR 1.06; P < .001), and lower prior use of methotrexate (aOR 0.44; P  =  .008), sulfasalazine (aOR 0.59; P  =  .003), and leflunomide (aOR 0.67; P  =  .013) were associated with D2T RA.

Study details: Findings are from a retrospective study including 2321 patients with RA from the Korean College of Rheumatology Biologics Registry who initiated or switched to b/tsDMARD, of which 271 patients had D2T RA.

Disclosures: This study was supported by a grant from the Yuhan Corporation, Seoul. The authors declared no conflicts of interest.

Source: Jung J-Y et al. Unveiling difficult-to-treat rheumatoid arthritis: Long-term impact of biologic or targeted synthetic DMARDs from the KOBIO registry. Arthritis Res Ther. 2023;25:174 (Sep 19). doi: 10.1186/s13075-023-03165-w

Key clinical point: Patients with difficult-to-treat (D2T) rheumatoid arthritis (RA) had a higher disease activity despite treatment with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) and demonstrated higher withdrawal rates due to inefficacy.

Major finding: Patients with vs without D2T RA had a higher Simplified Disease Activity Index (SDAI; P  =  .003) and higher withdrawal rates for b/tsDMARD due to inefficacy (P < .001). Higher SDAI (adjusted odds ratio [aOR] 1.06; P  =  .014), longer disease duration (aOR 1.06; P < .001), and lower prior use of methotrexate (aOR 0.44; P  =  .008), sulfasalazine (aOR 0.59; P  =  .003), and leflunomide (aOR 0.67; P  =  .013) were associated with D2T RA.

Study details: Findings are from a retrospective study including 2321 patients with RA from the Korean College of Rheumatology Biologics Registry who initiated or switched to b/tsDMARD, of which 271 patients had D2T RA.

Disclosures: This study was supported by a grant from the Yuhan Corporation, Seoul. The authors declared no conflicts of interest.

Source: Jung J-Y et al. Unveiling difficult-to-treat rheumatoid arthritis: Long-term impact of biologic or targeted synthetic DMARDs from the KOBIO registry. Arthritis Res Ther. 2023;25:174 (Sep 19). doi: 10.1186/s13075-023-03165-w

Key clinical point: Patients with difficult-to-treat (D2T) rheumatoid arthritis (RA) had a higher disease activity despite treatment with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) and demonstrated higher withdrawal rates due to inefficacy.

Major finding: Patients with vs without D2T RA had a higher Simplified Disease Activity Index (SDAI; P  =  .003) and higher withdrawal rates for b/tsDMARD due to inefficacy (P < .001). Higher SDAI (adjusted odds ratio [aOR] 1.06; P  =  .014), longer disease duration (aOR 1.06; P < .001), and lower prior use of methotrexate (aOR 0.44; P  =  .008), sulfasalazine (aOR 0.59; P  =  .003), and leflunomide (aOR 0.67; P  =  .013) were associated with D2T RA.

Study details: Findings are from a retrospective study including 2321 patients with RA from the Korean College of Rheumatology Biologics Registry who initiated or switched to b/tsDMARD, of which 271 patients had D2T RA.

Disclosures: This study was supported by a grant from the Yuhan Corporation, Seoul. The authors declared no conflicts of interest.

Source: Jung J-Y et al. Unveiling difficult-to-treat rheumatoid arthritis: Long-term impact of biologic or targeted synthetic DMARDs from the KOBIO registry. Arthritis Res Ther. 2023;25:174 (Sep 19). doi: 10.1186/s13075-023-03165-w

Key clinical point: Methotrexate-naive patients with rheumatoid arthritis (RA) showed varied joint-specific clinical responses to tofacitinib and methotrexate monotherapies, with those receiving methotrexate demonstrating more radiographic progression in the foot joints despite improved clinical response.

Major finding: At 12 months, tofacitinib vs methotrexate improved the clinical response in most tender and swollen joints, except some foot joints. Methotrexate improved the clinical response in most foot joints; however, radiographic progression was significantly worse with methotrexate vs tofacitinib (P < .05).

Study details: Findings are from a post hoc analysis of the phase 3 ORAL Start trial including 956 methotrexate-naive patients with RA who were randomly assigned to receive monotherapy with 5 mg (n = 373) or 10 mg (n = 397) tofacitinib or methotrexate (n = 186).

Disclosures: This study was sponsored by Pfizer, Inc. Four authors declared being current or former employees or shareholders of Pfizer or Syneos Health. Some authors declared receiving grants, honoraria, or research funding or having other ties with various sources, including Pfizer.

Source: Ciurea A et al. Joint-level responses to tofacitinib and methotrexate: A post hoc analysis of data from ORAL Start. Arthritis Res Ther. 2023;25:185 (Sep 29). doi: 10.1186/s13075-023-03144-1

Key clinical point: Methotrexate-naive patients with rheumatoid arthritis (RA) showed varied joint-specific clinical responses to tofacitinib and methotrexate monotherapies, with those receiving methotrexate demonstrating more radiographic progression in the foot joints despite improved clinical response.

Major finding: At 12 months, tofacitinib vs methotrexate improved the clinical response in most tender and swollen joints, except some foot joints. Methotrexate improved the clinical response in most foot joints; however, radiographic progression was significantly worse with methotrexate vs tofacitinib (P < .05).

Study details: Findings are from a post hoc analysis of the phase 3 ORAL Start trial including 956 methotrexate-naive patients with RA who were randomly assigned to receive monotherapy with 5 mg (n = 373) or 10 mg (n = 397) tofacitinib or methotrexate (n = 186).

Disclosures: This study was sponsored by Pfizer, Inc. Four authors declared being current or former employees or shareholders of Pfizer or Syneos Health. Some authors declared receiving grants, honoraria, or research funding or having other ties with various sources, including Pfizer.

Source: Ciurea A et al. Joint-level responses to tofacitinib and methotrexate: A post hoc analysis of data from ORAL Start. Arthritis Res Ther. 2023;25:185 (Sep 29). doi: 10.1186/s13075-023-03144-1

Key clinical point: Methotrexate-naive patients with rheumatoid arthritis (RA) showed varied joint-specific clinical responses to tofacitinib and methotrexate monotherapies, with those receiving methotrexate demonstrating more radiographic progression in the foot joints despite improved clinical response.

Major finding: At 12 months, tofacitinib vs methotrexate improved the clinical response in most tender and swollen joints, except some foot joints. Methotrexate improved the clinical response in most foot joints; however, radiographic progression was significantly worse with methotrexate vs tofacitinib (P < .05).

Study details: Findings are from a post hoc analysis of the phase 3 ORAL Start trial including 956 methotrexate-naive patients with RA who were randomly assigned to receive monotherapy with 5 mg (n = 373) or 10 mg (n = 397) tofacitinib or methotrexate (n = 186).

Disclosures: This study was sponsored by Pfizer, Inc. Four authors declared being current or former employees or shareholders of Pfizer or Syneos Health. Some authors declared receiving grants, honoraria, or research funding or having other ties with various sources, including Pfizer.

Source: Ciurea A et al. Joint-level responses to tofacitinib and methotrexate: A post hoc analysis of data from ORAL Start. Arthritis Res Ther. 2023;25:185 (Sep 29). doi: 10.1186/s13075-023-03144-1

Key clinical point: Younger age, higher disease activity, prevalent erosions, and monotherapy were significant risk factors for the development of new bone erosions in biologic disease-modifying antirheumatic drug (bDMARD)-treated patients with rheumatoid arthritis (RA).

Major finding: Risk of developing new bone erosions increased with younger age (adjusted odds ratio [aOR] 0.970; P < .001), higher Disease Activity Scores for 28 Joints-C-Reactive Protein (aOR per point increase 5.349; P < .001), presence of erosions at baseline (aOR 7.820; P < .001), and conventional DMARD-naive status (aOR 2.068; P  =  .033).

Study details: Findings are from a retrospective analysis of prospectively collected data of 578 patients with RA who started bDMARD treatment.

Disclosures: This study did not receive any funding. G Adami, D Gatti, and M Rossini declared receiving personal fees or serving as a consultant or speaker for various sources. The other authors declared no conflicts of interest.

Source: Adami G et al. Factors associated with radiographic progression in rheumatoid arthritis starting biological diseases modifying anti-rheumatic drugs (bDMARDs). Ther Adv Musculoskelet Dis. 2023;15:1759720X231174534 (Sep 28). doi: 10.1177/1759720X231174534

Key clinical point: Younger age, higher disease activity, prevalent erosions, and monotherapy were significant risk factors for the development of new bone erosions in biologic disease-modifying antirheumatic drug (bDMARD)-treated patients with rheumatoid arthritis (RA).

Major finding: Risk of developing new bone erosions increased with younger age (adjusted odds ratio [aOR] 0.970; P < .001), higher Disease Activity Scores for 28 Joints-C-Reactive Protein (aOR per point increase 5.349; P < .001), presence of erosions at baseline (aOR 7.820; P < .001), and conventional DMARD-naive status (aOR 2.068; P  =  .033).

Study details: Findings are from a retrospective analysis of prospectively collected data of 578 patients with RA who started bDMARD treatment.

Disclosures: This study did not receive any funding. G Adami, D Gatti, and M Rossini declared receiving personal fees or serving as a consultant or speaker for various sources. The other authors declared no conflicts of interest.

Source: Adami G et al. Factors associated with radiographic progression in rheumatoid arthritis starting biological diseases modifying anti-rheumatic drugs (bDMARDs). Ther Adv Musculoskelet Dis. 2023;15:1759720X231174534 (Sep 28). doi: 10.1177/1759720X231174534

Key clinical point: Younger age, higher disease activity, prevalent erosions, and monotherapy were significant risk factors for the development of new bone erosions in biologic disease-modifying antirheumatic drug (bDMARD)-treated patients with rheumatoid arthritis (RA).

Major finding: Risk of developing new bone erosions increased with younger age (adjusted odds ratio [aOR] 0.970; P < .001), higher Disease Activity Scores for 28 Joints-C-Reactive Protein (aOR per point increase 5.349; P < .001), presence of erosions at baseline (aOR 7.820; P < .001), and conventional DMARD-naive status (aOR 2.068; P  =  .033).

Study details: Findings are from a retrospective analysis of prospectively collected data of 578 patients with RA who started bDMARD treatment.

Disclosures: This study did not receive any funding. G Adami, D Gatti, and M Rossini declared receiving personal fees or serving as a consultant or speaker for various sources. The other authors declared no conflicts of interest.

Source: Adami G et al. Factors associated with radiographic progression in rheumatoid arthritis starting biological diseases modifying anti-rheumatic drugs (bDMARDs). Ther Adv Musculoskelet Dis. 2023;15:1759720X231174534 (Sep 28). doi: 10.1177/1759720X231174534

Key clinical point: Abatacept improved disease activity in patients with moderate-to-severe rheumatoid arthritis (RA), with those managed with treat-to-target (T2T) approach being more likely to achieve low disease activity (LDA) compared with routine care (RC).

Major finding: In each treatment group, abatacept treatment led to early and sustained improvement in disease activity (P < .0001). However, the odds of achieving Clinical Disease Activity Index LDA were significantly higher with T2T vs RC approach (odds ratio 1.33; P  =  .0263).

Study details: Findings are from the 12-month prospective, randomized Abatacept Best Care trial including 284 patients with moderate-to-severely active RA who initiated abatacept as first- or second-line biologic therapy and were randomly assigned to the T2T (n = 130) or RC (n = 154) group.

Disclosures: This study was managed by JSS Medical Research, and the trial was funded by Bristol Myers Squibb (BMS). Three authors declared being employees of or holding stock or stock options in BMS or JSS Medical Research. Several authors declared ties with various sources, including BMS.

Source: Bessette L et al. Effectiveness of a treat-to-target strategy in patients with moderate to severely active rheumatoid arthritis treated with abatacept. Arthritis Res Ther. 2023;25:183 (Sep 28). doi: 10.1186/s13075-023-03151-2

Key clinical point: Abatacept improved disease activity in patients with moderate-to-severe rheumatoid arthritis (RA), with those managed with treat-to-target (T2T) approach being more likely to achieve low disease activity (LDA) compared with routine care (RC).

Major finding: In each treatment group, abatacept treatment led to early and sustained improvement in disease activity (P < .0001). However, the odds of achieving Clinical Disease Activity Index LDA were significantly higher with T2T vs RC approach (odds ratio 1.33; P  =  .0263).

Study details: Findings are from the 12-month prospective, randomized Abatacept Best Care trial including 284 patients with moderate-to-severely active RA who initiated abatacept as first- or second-line biologic therapy and were randomly assigned to the T2T (n = 130) or RC (n = 154) group.

Disclosures: This study was managed by JSS Medical Research, and the trial was funded by Bristol Myers Squibb (BMS). Three authors declared being employees of or holding stock or stock options in BMS or JSS Medical Research. Several authors declared ties with various sources, including BMS.

Source: Bessette L et al. Effectiveness of a treat-to-target strategy in patients with moderate to severely active rheumatoid arthritis treated with abatacept. Arthritis Res Ther. 2023;25:183 (Sep 28). doi: 10.1186/s13075-023-03151-2

Key clinical point: Abatacept improved disease activity in patients with moderate-to-severe rheumatoid arthritis (RA), with those managed with treat-to-target (T2T) approach being more likely to achieve low disease activity (LDA) compared with routine care (RC).

Major finding: In each treatment group, abatacept treatment led to early and sustained improvement in disease activity (P < .0001). However, the odds of achieving Clinical Disease Activity Index LDA were significantly higher with T2T vs RC approach (odds ratio 1.33; P  =  .0263).

Study details: Findings are from the 12-month prospective, randomized Abatacept Best Care trial including 284 patients with moderate-to-severely active RA who initiated abatacept as first- or second-line biologic therapy and were randomly assigned to the T2T (n = 130) or RC (n = 154) group.

Disclosures: This study was managed by JSS Medical Research, and the trial was funded by Bristol Myers Squibb (BMS). Three authors declared being employees of or holding stock or stock options in BMS or JSS Medical Research. Several authors declared ties with various sources, including BMS.

Source: Bessette L et al. Effectiveness of a treat-to-target strategy in patients with moderate to severely active rheumatoid arthritis treated with abatacept. Arthritis Res Ther. 2023;25:183 (Sep 28). doi: 10.1186/s13075-023-03151-2