Rheumatoid Arthritis

With several new biologic (b) disease-modifying antirheumatic drugs (DMARD) and targeted synthetic (ts) DMARD now available for the treatment of rheumatoid arthritis (RA), information regarding their comparative effectiveness would be of interest. Relatively few head-to-head trials have been published, however. Though "real-world" studies have been published to provide some information about comparative effectiveness, Deakin and colleagues used a target trial emulation framework to apply clinical trial methods to real-world data. Using the Australian OPAL registry of bDMARD/tsDMARD-naive patients, they developed a randomized controlled trial protocol of tofacitinib vs adalimumab using an intention-to-treat analysis. Under this framework, there was small reduction of disease activity with tofacitinib vs adalimumab at 3 months and no difference at 9 months. While this framework is conceptually interesting, it may be more meaningful used in side-by-side comparison to a real-world analysis of the same data to evaluate pitfalls and biases in both; otherwise, its utility as a stand-alone analysis of observational data is not fully clear.

Østergaard and colleagues also performed a head-to-head study of several different therapies to address the question of optimal treatment strategies for patients with early RA. Patients with moderate to severe disease activity were randomly assigned to treatment with methotrexate combined with (1) oral glucocorticoid or sulfasalazine, hydroxychloroquine, and intra-articular steroid injections, (2) certolizumab, (3) abatacept, or (4) tocilizumab. Disease activity and radiographic changes were evaluated at 48 weeks. In this study of over 800 patients, treatment with abatacept or certolizumab was associated with improved Clinical Disease Activity Index (CDAI) remission rates compared with the active conventional therapy (group 1), but tocilizumab was not. The overall differences between bDMARD treatment groups were small and thus may not reflect significant differences in effectiveness. Instead, this study challenges the notion of initiating conventional synthetic DMARD (csDMARD) therapy in patients with early RA and stepping up to bDMARD, as initial bDMARD therapy may be of benefit in patients with more active early RA.

Alongside the question of the effectiveness of bMARD and tsDMARD in real-world settings, the appropriate role for long-term low-dose prednisone in the treatment of RA remains unknown. A recent study by Güler-Yüksel and colleagues examined the effects of 5 mg prednisolone daily in addition to standard therapy in patients over 65 years of age with active RA. Due to the potential complications of weight gain and glucose intolerance with long-term glucocorticoids, in addition to low-bone-density issues, their use has generally not been viewed favorably. In this multicenter trial, 449 patients were randomly assigned to receive prednisolone vs placebo in addition to their usual medications over 2 years. Notably, patients in the prednisolone group had an average of 0.9 kg weight gain compared with placebo with 0.4 kg weight loss over 2 years. By the end of 2 years, 29% of patients in the prednisolone group had a weight gain of > 2 kg compared with 18% of patients in the placebo group. Only 57 patients in all underwent body composition analysis, and, interestingly, those in the prednisolone group had small increases in lean body mass compared with fat mass, though these patients were not necessarily representative. The authors suggest, though the study does not prove, that low-dose prednisolone can be protective against sarcopenia, which is associated with older age and "rheumatoid cachexia." The study also did not examine the interaction of glucocorticoid use with diet and exercise. While it is reassuring that patients in this study did not experience major weight gain, it does not appear to be a generalizable finding at this point.

With several new biologic (b) disease-modifying antirheumatic drugs (DMARD) and targeted synthetic (ts) DMARD now available for the treatment of rheumatoid arthritis (RA), information regarding their comparative effectiveness would be of interest. Relatively few head-to-head trials have been published, however. Though "real-world" studies have been published to provide some information about comparative effectiveness, Deakin and colleagues used a target trial emulation framework to apply clinical trial methods to real-world data. Using the Australian OPAL registry of bDMARD/tsDMARD-naive patients, they developed a randomized controlled trial protocol of tofacitinib vs adalimumab using an intention-to-treat analysis. Under this framework, there was small reduction of disease activity with tofacitinib vs adalimumab at 3 months and no difference at 9 months. While this framework is conceptually interesting, it may be more meaningful used in side-by-side comparison to a real-world analysis of the same data to evaluate pitfalls and biases in both; otherwise, its utility as a stand-alone analysis of observational data is not fully clear.

Østergaard and colleagues also performed a head-to-head study of several different therapies to address the question of optimal treatment strategies for patients with early RA. Patients with moderate to severe disease activity were randomly assigned to treatment with methotrexate combined with (1) oral glucocorticoid or sulfasalazine, hydroxychloroquine, and intra-articular steroid injections, (2) certolizumab, (3) abatacept, or (4) tocilizumab. Disease activity and radiographic changes were evaluated at 48 weeks. In this study of over 800 patients, treatment with abatacept or certolizumab was associated with improved Clinical Disease Activity Index (CDAI) remission rates compared with the active conventional therapy (group 1), but tocilizumab was not. The overall differences between bDMARD treatment groups were small and thus may not reflect significant differences in effectiveness. Instead, this study challenges the notion of initiating conventional synthetic DMARD (csDMARD) therapy in patients with early RA and stepping up to bDMARD, as initial bDMARD therapy may be of benefit in patients with more active early RA.

Alongside the question of the effectiveness of bMARD and tsDMARD in real-world settings, the appropriate role for long-term low-dose prednisone in the treatment of RA remains unknown. A recent study by Güler-Yüksel and colleagues examined the effects of 5 mg prednisolone daily in addition to standard therapy in patients over 65 years of age with active RA. Due to the potential complications of weight gain and glucose intolerance with long-term glucocorticoids, in addition to low-bone-density issues, their use has generally not been viewed favorably. In this multicenter trial, 449 patients were randomly assigned to receive prednisolone vs placebo in addition to their usual medications over 2 years. Notably, patients in the prednisolone group had an average of 0.9 kg weight gain compared with placebo with 0.4 kg weight loss over 2 years. By the end of 2 years, 29% of patients in the prednisolone group had a weight gain of > 2 kg compared with 18% of patients in the placebo group. Only 57 patients in all underwent body composition analysis, and, interestingly, those in the prednisolone group had small increases in lean body mass compared with fat mass, though these patients were not necessarily representative. The authors suggest, though the study does not prove, that low-dose prednisolone can be protective against sarcopenia, which is associated with older age and "rheumatoid cachexia." The study also did not examine the interaction of glucocorticoid use with diet and exercise. While it is reassuring that patients in this study did not experience major weight gain, it does not appear to be a generalizable finding at this point.

With several new biologic (b) disease-modifying antirheumatic drugs (DMARD) and targeted synthetic (ts) DMARD now available for the treatment of rheumatoid arthritis (RA), information regarding their comparative effectiveness would be of interest. Relatively few head-to-head trials have been published, however. Though "real-world" studies have been published to provide some information about comparative effectiveness, Deakin and colleagues used a target trial emulation framework to apply clinical trial methods to real-world data. Using the Australian OPAL registry of bDMARD/tsDMARD-naive patients, they developed a randomized controlled trial protocol of tofacitinib vs adalimumab using an intention-to-treat analysis. Under this framework, there was small reduction of disease activity with tofacitinib vs adalimumab at 3 months and no difference at 9 months. While this framework is conceptually interesting, it may be more meaningful used in side-by-side comparison to a real-world analysis of the same data to evaluate pitfalls and biases in both; otherwise, its utility as a stand-alone analysis of observational data is not fully clear.

Østergaard and colleagues also performed a head-to-head study of several different therapies to address the question of optimal treatment strategies for patients with early RA. Patients with moderate to severe disease activity were randomly assigned to treatment with methotrexate combined with (1) oral glucocorticoid or sulfasalazine, hydroxychloroquine, and intra-articular steroid injections, (2) certolizumab, (3) abatacept, or (4) tocilizumab. Disease activity and radiographic changes were evaluated at 48 weeks. In this study of over 800 patients, treatment with abatacept or certolizumab was associated with improved Clinical Disease Activity Index (CDAI) remission rates compared with the active conventional therapy (group 1), but tocilizumab was not. The overall differences between bDMARD treatment groups were small and thus may not reflect significant differences in effectiveness. Instead, this study challenges the notion of initiating conventional synthetic DMARD (csDMARD) therapy in patients with early RA and stepping up to bDMARD, as initial bDMARD therapy may be of benefit in patients with more active early RA.

Alongside the question of the effectiveness of bMARD and tsDMARD in real-world settings, the appropriate role for long-term low-dose prednisone in the treatment of RA remains unknown. A recent study by Güler-Yüksel and colleagues examined the effects of 5 mg prednisolone daily in addition to standard therapy in patients over 65 years of age with active RA. Due to the potential complications of weight gain and glucose intolerance with long-term glucocorticoids, in addition to low-bone-density issues, their use has generally not been viewed favorably. In this multicenter trial, 449 patients were randomly assigned to receive prednisolone vs placebo in addition to their usual medications over 2 years. Notably, patients in the prednisolone group had an average of 0.9 kg weight gain compared with placebo with 0.4 kg weight loss over 2 years. By the end of 2 years, 29% of patients in the prednisolone group had a weight gain of > 2 kg compared with 18% of patients in the placebo group. Only 57 patients in all underwent body composition analysis, and, interestingly, those in the prednisolone group had small increases in lean body mass compared with fat mass, though these patients were not necessarily representative. The authors suggest, though the study does not prove, that low-dose prednisolone can be protective against sarcopenia, which is associated with older age and "rheumatoid cachexia." The study also did not examine the interaction of glucocorticoid use with diet and exercise. While it is reassuring that patients in this study did not experience major weight gain, it does not appear to be a generalizable finding at this point.

A new model can predict which patients are more likely to experience side effects from long-term methotrexate (MTX) use, research suggests. Patients with a lower risk profile may benefit from less frequent testing, the authors hypothesize.

Most recommendations advise that patients initiating MTX therapy should get blood testing every 2-4 weeks to monitor for full blood count, liver function, urea electrolytes, and creatinine. After 6 months taking MTX, monitoring can be tapered to every 3 months. But Abhishek Abhishek, MD, PhD, professor of rheumatology and honorary consultant rheumatologist at Nottingham (England) University Hospitals NHS Trust and colleagues argue that abnormal results after the initial 6 months of treatment are “infrequent,” and patients may benefit from fewer tests throughout the year.

ftwitty/E+/Getty Images

“Unnecessary blood tests waste patients’ time and health care resources, including the time of general practitioners and phlebotomists,” Dr. Abhishek and associates write. “It would be beneficial to predict the risk of clinically significant abnormal blood test results during long-term methotrexate treatment to inform the frequency of testing for individuals.”
 

Stratifying risk

In the study, published in the BMJ, researchers used the UK’s Clinical Practice Research Datalink (CPRD) to identify the electronic medical records of over 37,000 adult patients with an immune-mediated inflammatory disease who were prescribed MTX during 2007-2019. All included patients were prescribed MTX for at least 6 months. The main outcome was discontinuation of methotrexate because of abnormal blood test results. Around 62% of patients had rheumatoid arthritis and 22% had psoriasis or psoriatic arthritis.

Using these anonymized data, the group developed a risk stratification model using 11 clinical predictors. “The factors that went in the model are simple things that most patients can self-report or doctors can get from their patient’s medical records,” Dr. Abhishek told this news organization, including methotrexate dose, age, sex, and comorbidities. Dr. Abhishek emphasized that the model should be used only in patients who have continued taking MTX for at least 6 months and have already undergone more frequent initial testing.

The strongest individual predictors were diabetes (hazard ratio, 1.25), chronic kidney disease stage 3 (HR, 2.01), and previous cytopenia or raised liver enzyme levels during the first 6 months of MTX therapy (HR, 2.97). However, Dr. Abhishek emphasized that the individual factors were less important, noting that the model sums the risks to predict outcomes more accurately. Most patients (68.4%) were sorted into the low-risk cohort, with a less than 10% estimated risk of discontinuing MTX over the next 5 years. About one-fifth (20.9%) were categorized as moderate risk (10%-20% estimated risk over 5 years), and 10.7% were high risk, with a greater than 20% estimated risk of discontinuing the drug over 5 years.

The authors argue that low-risk patients could receive less frequent testing – perhaps every 6 months or annually, while moderate-risk patients would continue to be tested every 3 months. High-risk patients could potentially be tested with even greater frequently.
 

More research needed

The research involved “incredibly sophisticated statistical analysis,” said Daniel E. Furst, MD, professor emeritus of medicine at the University of California, Los Angeles, who was not involved with the study. However, the data do not yet support altering blood testing frequency based on this model.

“The hypothesis that not all patients have to be examined so frequently is a very reasonable hypothesis,” Dr. Furst said in an interview, and additional research is needed to corroborate it. The model also needs to be validated in patient populations outside of the United Kingdom, he added.

Dr. Abhishek agreed that validating the model in other patient populations is an important next step. “When we develop a tool [using] a one-nation data set, we want other researchers to then validate it in other countries’ data sets to make sure there is nothing odd about patients in the U.K. that makes the tool work well here but not in [the] U.S., Europe, or Asia, for example,” he said. Doing so should be relatively easy, he said, as the model is publicly available, and the information required is routinely collected during clinic visits.

To understand if less frequent testing might be appropriate for some patients, researchers would need to look at data registries like the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS) registry or CorEvitas registries “where the testing is done in a very regular way over the long haul,” Dr. Furst said. Analyzing these datasets, researchers could determine the testing intervals that would be most efficient for low- and high-risk patients.
 

A word of caution

While less frequent testing for long-term MTX therapy could likely have benefits, there is still some risk involved, cautioned Prabha Ranganathan, MD, professor of medicine at Washington University in St. Louis.

“Although most methotrexate toxicity occurs within the first 6 months of starting treatment, rare idiosyncratic toxicity can occur that does not correlate with the dose, duration, or method of how methotrexate is administered,” she wrote in an accompanying editorial. “Most rheumatologists can identify a handful of patients who receive methotrexate in their practice who develop sudden leukopenia or thrombocytopenia or transaminitis that is severe enough to warrant drug discontinuation.” While tools like this prediction model can be useful, clinicians need to consider each patient individually and use shared decision-making when monitoring for MTX toxicity, she advised.

“As in most of areas of medicine, the one-size-fits-all approach does not work for methotrexate users,” she noted.

This study was funded by the U.K. National Institute for Health and Care Research and Health Technology Assessment. Dr. Abhishek has received institutional research grants from AstraZeneca and Oxford Immunotech and personal fees from UpToDate, Springer, Cadila Pharmaceuticals, NGM Bio, Limbic, and Inflazome. Dr. Furst and Dr. Ranganathan report no relevant financial relationships.

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

A new model can predict which patients are more likely to experience side effects from long-term methotrexate (MTX) use, research suggests. Patients with a lower risk profile may benefit from less frequent testing, the authors hypothesize.

Most recommendations advise that patients initiating MTX therapy should get blood testing every 2-4 weeks to monitor for full blood count, liver function, urea electrolytes, and creatinine. After 6 months taking MTX, monitoring can be tapered to every 3 months. But Abhishek Abhishek, MD, PhD, professor of rheumatology and honorary consultant rheumatologist at Nottingham (England) University Hospitals NHS Trust and colleagues argue that abnormal results after the initial 6 months of treatment are “infrequent,” and patients may benefit from fewer tests throughout the year.

ftwitty/E+/Getty Images

“Unnecessary blood tests waste patients’ time and health care resources, including the time of general practitioners and phlebotomists,” Dr. Abhishek and associates write. “It would be beneficial to predict the risk of clinically significant abnormal blood test results during long-term methotrexate treatment to inform the frequency of testing for individuals.”
 

Stratifying risk

In the study, published in the BMJ, researchers used the UK’s Clinical Practice Research Datalink (CPRD) to identify the electronic medical records of over 37,000 adult patients with an immune-mediated inflammatory disease who were prescribed MTX during 2007-2019. All included patients were prescribed MTX for at least 6 months. The main outcome was discontinuation of methotrexate because of abnormal blood test results. Around 62% of patients had rheumatoid arthritis and 22% had psoriasis or psoriatic arthritis.

Using these anonymized data, the group developed a risk stratification model using 11 clinical predictors. “The factors that went in the model are simple things that most patients can self-report or doctors can get from their patient’s medical records,” Dr. Abhishek told this news organization, including methotrexate dose, age, sex, and comorbidities. Dr. Abhishek emphasized that the model should be used only in patients who have continued taking MTX for at least 6 months and have already undergone more frequent initial testing.

The strongest individual predictors were diabetes (hazard ratio, 1.25), chronic kidney disease stage 3 (HR, 2.01), and previous cytopenia or raised liver enzyme levels during the first 6 months of MTX therapy (HR, 2.97). However, Dr. Abhishek emphasized that the individual factors were less important, noting that the model sums the risks to predict outcomes more accurately. Most patients (68.4%) were sorted into the low-risk cohort, with a less than 10% estimated risk of discontinuing MTX over the next 5 years. About one-fifth (20.9%) were categorized as moderate risk (10%-20% estimated risk over 5 years), and 10.7% were high risk, with a greater than 20% estimated risk of discontinuing the drug over 5 years.

The authors argue that low-risk patients could receive less frequent testing – perhaps every 6 months or annually, while moderate-risk patients would continue to be tested every 3 months. High-risk patients could potentially be tested with even greater frequently.
 

More research needed

The research involved “incredibly sophisticated statistical analysis,” said Daniel E. Furst, MD, professor emeritus of medicine at the University of California, Los Angeles, who was not involved with the study. However, the data do not yet support altering blood testing frequency based on this model.

“The hypothesis that not all patients have to be examined so frequently is a very reasonable hypothesis,” Dr. Furst said in an interview, and additional research is needed to corroborate it. The model also needs to be validated in patient populations outside of the United Kingdom, he added.

Dr. Abhishek agreed that validating the model in other patient populations is an important next step. “When we develop a tool [using] a one-nation data set, we want other researchers to then validate it in other countries’ data sets to make sure there is nothing odd about patients in the U.K. that makes the tool work well here but not in [the] U.S., Europe, or Asia, for example,” he said. Doing so should be relatively easy, he said, as the model is publicly available, and the information required is routinely collected during clinic visits.

To understand if less frequent testing might be appropriate for some patients, researchers would need to look at data registries like the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS) registry or CorEvitas registries “where the testing is done in a very regular way over the long haul,” Dr. Furst said. Analyzing these datasets, researchers could determine the testing intervals that would be most efficient for low- and high-risk patients.
 

A word of caution

While less frequent testing for long-term MTX therapy could likely have benefits, there is still some risk involved, cautioned Prabha Ranganathan, MD, professor of medicine at Washington University in St. Louis.

“Although most methotrexate toxicity occurs within the first 6 months of starting treatment, rare idiosyncratic toxicity can occur that does not correlate with the dose, duration, or method of how methotrexate is administered,” she wrote in an accompanying editorial. “Most rheumatologists can identify a handful of patients who receive methotrexate in their practice who develop sudden leukopenia or thrombocytopenia or transaminitis that is severe enough to warrant drug discontinuation.” While tools like this prediction model can be useful, clinicians need to consider each patient individually and use shared decision-making when monitoring for MTX toxicity, she advised.

“As in most of areas of medicine, the one-size-fits-all approach does not work for methotrexate users,” she noted.

This study was funded by the U.K. National Institute for Health and Care Research and Health Technology Assessment. Dr. Abhishek has received institutional research grants from AstraZeneca and Oxford Immunotech and personal fees from UpToDate, Springer, Cadila Pharmaceuticals, NGM Bio, Limbic, and Inflazome. Dr. Furst and Dr. Ranganathan report no relevant financial relationships.

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

A new model can predict which patients are more likely to experience side effects from long-term methotrexate (MTX) use, research suggests. Patients with a lower risk profile may benefit from less frequent testing, the authors hypothesize.

Most recommendations advise that patients initiating MTX therapy should get blood testing every 2-4 weeks to monitor for full blood count, liver function, urea electrolytes, and creatinine. After 6 months taking MTX, monitoring can be tapered to every 3 months. But Abhishek Abhishek, MD, PhD, professor of rheumatology and honorary consultant rheumatologist at Nottingham (England) University Hospitals NHS Trust and colleagues argue that abnormal results after the initial 6 months of treatment are “infrequent,” and patients may benefit from fewer tests throughout the year.

ftwitty/E+/Getty Images

“Unnecessary blood tests waste patients’ time and health care resources, including the time of general practitioners and phlebotomists,” Dr. Abhishek and associates write. “It would be beneficial to predict the risk of clinically significant abnormal blood test results during long-term methotrexate treatment to inform the frequency of testing for individuals.”
 

Stratifying risk

In the study, published in the BMJ, researchers used the UK’s Clinical Practice Research Datalink (CPRD) to identify the electronic medical records of over 37,000 adult patients with an immune-mediated inflammatory disease who were prescribed MTX during 2007-2019. All included patients were prescribed MTX for at least 6 months. The main outcome was discontinuation of methotrexate because of abnormal blood test results. Around 62% of patients had rheumatoid arthritis and 22% had psoriasis or psoriatic arthritis.

Using these anonymized data, the group developed a risk stratification model using 11 clinical predictors. “The factors that went in the model are simple things that most patients can self-report or doctors can get from their patient’s medical records,” Dr. Abhishek told this news organization, including methotrexate dose, age, sex, and comorbidities. Dr. Abhishek emphasized that the model should be used only in patients who have continued taking MTX for at least 6 months and have already undergone more frequent initial testing.

The strongest individual predictors were diabetes (hazard ratio, 1.25), chronic kidney disease stage 3 (HR, 2.01), and previous cytopenia or raised liver enzyme levels during the first 6 months of MTX therapy (HR, 2.97). However, Dr. Abhishek emphasized that the individual factors were less important, noting that the model sums the risks to predict outcomes more accurately. Most patients (68.4%) were sorted into the low-risk cohort, with a less than 10% estimated risk of discontinuing MTX over the next 5 years. About one-fifth (20.9%) were categorized as moderate risk (10%-20% estimated risk over 5 years), and 10.7% were high risk, with a greater than 20% estimated risk of discontinuing the drug over 5 years.

The authors argue that low-risk patients could receive less frequent testing – perhaps every 6 months or annually, while moderate-risk patients would continue to be tested every 3 months. High-risk patients could potentially be tested with even greater frequently.
 

More research needed

The research involved “incredibly sophisticated statistical analysis,” said Daniel E. Furst, MD, professor emeritus of medicine at the University of California, Los Angeles, who was not involved with the study. However, the data do not yet support altering blood testing frequency based on this model.

“The hypothesis that not all patients have to be examined so frequently is a very reasonable hypothesis,” Dr. Furst said in an interview, and additional research is needed to corroborate it. The model also needs to be validated in patient populations outside of the United Kingdom, he added.

Dr. Abhishek agreed that validating the model in other patient populations is an important next step. “When we develop a tool [using] a one-nation data set, we want other researchers to then validate it in other countries’ data sets to make sure there is nothing odd about patients in the U.K. that makes the tool work well here but not in [the] U.S., Europe, or Asia, for example,” he said. Doing so should be relatively easy, he said, as the model is publicly available, and the information required is routinely collected during clinic visits.

To understand if less frequent testing might be appropriate for some patients, researchers would need to look at data registries like the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS) registry or CorEvitas registries “where the testing is done in a very regular way over the long haul,” Dr. Furst said. Analyzing these datasets, researchers could determine the testing intervals that would be most efficient for low- and high-risk patients.
 

A word of caution

While less frequent testing for long-term MTX therapy could likely have benefits, there is still some risk involved, cautioned Prabha Ranganathan, MD, professor of medicine at Washington University in St. Louis.

“Although most methotrexate toxicity occurs within the first 6 months of starting treatment, rare idiosyncratic toxicity can occur that does not correlate with the dose, duration, or method of how methotrexate is administered,” she wrote in an accompanying editorial. “Most rheumatologists can identify a handful of patients who receive methotrexate in their practice who develop sudden leukopenia or thrombocytopenia or transaminitis that is severe enough to warrant drug discontinuation.” While tools like this prediction model can be useful, clinicians need to consider each patient individually and use shared decision-making when monitoring for MTX toxicity, she advised.

“As in most of areas of medicine, the one-size-fits-all approach does not work for methotrexate users,” she noted.

This study was funded by the U.K. National Institute for Health and Care Research and Health Technology Assessment. Dr. Abhishek has received institutional research grants from AstraZeneca and Oxford Immunotech and personal fees from UpToDate, Springer, Cadila Pharmaceuticals, NGM Bio, Limbic, and Inflazome. Dr. Furst and Dr. Ranganathan report no relevant financial relationships.

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

Noninvasive auricular vagus nerve stimulation (VNS) is no more effective than placebo at controlling symptoms of rheumatoid arthritis, according to a new study. But experts emphasize that these results do not mean trials of different forms of VNS will have the same fate.

VNS offers a potential additional therapy for autoimmune disease beyond disease-modifying antirheumatic drugs, explained first author Matthew Baker, MD, clinical chief, division of immunology and rheumatology, Stanford (Calif.) University, and colleagues.

“The principle of VNS is based upon the inflammatory reflex, which describes a primitive connection between the nervous system and immune system,” the authors write. Signals sent down the vagus nerve to the splenic nerve stimulate immune cells in the spleen, which ultimately results in blocking production of inflammatory cytokines such as tumor necrosis factor. “It is hypothesized that this reduction in systemic inflammation can be harnessed for the treatment of diseases such as RA,” they continue, and smaller studies suggest this treatment could benefit patients.

In a previous 12-week, open-label trial, 17 patients with RA who were implanted with a VNS device on the left cervical vagus nerve saw improvement in RA symptoms, as well as a decrease in TNF production. Noninvasive devices that stimulate the auricular branch of the vagus nerve have also shown some promise. A sham-controlled study of 18 patients with systemic lupus erythematosus (SLE) found that patients who received transcutaneous auricular VNS reported reduced musculoskeletal pain over just 4 days. An open-label study of 30 patients with RA showed clinically significant reductions in disease activity score of 28 joints with C-reactive protein (DAS28-CRP) and clinical improvement in American College of Rheumatology responses over 12 weeks. Additional trials have also demonstrated this positive effect of noninvasive VNS on RA symptoms, but all studies conducted thus far have been relatively small or uncontrolled, Dr. Baker said.
 

Results of latest trial

In this new trial, published online in Arthritis & Rheumatology, researchers enrolled 113 patients with active RA who had inadequate responses or intolerance to conventional synthetic DMARDs and were naïve to biologic or targeted synthetic DMARDs. All patients were given an auricular vagus nerve stimulator via a custom-molded earpiece that was controlled by a smartphone app. Patients wore the device for 15 minutes each day. When worn and turned on, the device generated electrical signals delivered transcutaneously to the cymba concha, a region of the ear connected to the auricular branch of the vagus nerve. This stimulation is imperceptible to patients, Dr. Baker explained. “For the sham arm, we simply did not turn the device on at all,” he said. A subject in the sham arm would use the same device on a 15-minute timer, but no stimulation was given.

After 12 weeks, researchers found no statistically significant difference between the treatment and sham arms in achieving 20% improvement in ACR response criteria or mean change in DAS28-CRP. A total of 17 patients, including 12 in the treatment arm, reported adverse events during the study, and all events were categorized as mild to moderate.

While the research team was “obviously disappointed” about the results, Dr. Baker said, negative findings in trials also are important. “The real value of our study is pointing out the need for large controlled, sham-controlled studies,” he said, especially for potential treatments with a lot of enthusiasm behind them.
 

Results don’t seal the fate of other VNS approaches

“As a properly controlled trial, the results are impressively negative,” writes Roy Fleischmann, MD, clinical professor of medicine, University of Texas Southwestern Medical Center, and codirector, Metroplex Clinical Research Center, both in Dallas, in an editorial about the study. Many of the previous studies looking at this therapy in RA were open label, which could bias the results, he argued. The biggest question, he noted, is if other blinded, sham-controlled trials looking at VNS devices will show similar results.

By itself, this finding does not imply that other VNS devices will be unsuccessful, argued Jonathan Kay, MD, the Timothy S. and Elaine L. Peterson chair in rheumatology, and professor of medicine and population and quantitative health sciences, UMass Chan Medical School and UMass Memorial Medical Center, both in Worcester, Mass. He is also an investigator for the RESET-RA trial, a randomized, sham-controlled trial that will assess the safety and efficacy of an implantable VNS device in an estimated 250 patients with RA. He was not involved with Dr. Baker’s work.

“Auricular VNS is delivered more distally than cervical or splenic nerve stimulation,” Dr. Kay said, and the potential effect of these other forms of VNS may have different outcomes.

Cynthia Aranow, MD, rheumatologist and director of the Clinical Autoimmunity Center of Excellence at Feinstein Institutes for Medical Research, Manhasset, New York, agreed with Dr. Kay, noting that direct VNS stimulation via implantable device and transcutaneous stimulation through the skin are not comparable. She also is unaffiliated with the study.

“This group conducted a well-designed, sham-controlled study of a reasonable number of patients and over a reasonable period of time and observed no significant differences between those participants receiving true and those participants receiving sham stimulation,” she wrote in an email. “However, it’s important to point out that the stimulation settings used in this study were kHz (kilohertz) which is 1,000 times greater than the settings used in multiple other studies in which transauricular VNS has been shown to be clinically effective, including studies in long COVID, tinnitus, SLE, cluster headaches, erosive hand osteoarthritis, pediatric kidney disease, among others,” she said.

The role for VNS treatment, whether direct stimulation via implantable device or transcutaneous, in autoimmune and inflammatory diseases “remains to be determined by future studies,” she said.

The study was funded by Nesos. Dr. Baker received personal fees from Nesos during the study. Dr. Kay has received consulting fees from AbbVie, Boehringer Ingelheim, Celltrion Healthcare, and several other pharmaceutical companies. Dr. Aranow reports no relevant financial relationships.

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

Noninvasive auricular vagus nerve stimulation (VNS) is no more effective than placebo at controlling symptoms of rheumatoid arthritis, according to a new study. But experts emphasize that these results do not mean trials of different forms of VNS will have the same fate.

VNS offers a potential additional therapy for autoimmune disease beyond disease-modifying antirheumatic drugs, explained first author Matthew Baker, MD, clinical chief, division of immunology and rheumatology, Stanford (Calif.) University, and colleagues.

“The principle of VNS is based upon the inflammatory reflex, which describes a primitive connection between the nervous system and immune system,” the authors write. Signals sent down the vagus nerve to the splenic nerve stimulate immune cells in the spleen, which ultimately results in blocking production of inflammatory cytokines such as tumor necrosis factor. “It is hypothesized that this reduction in systemic inflammation can be harnessed for the treatment of diseases such as RA,” they continue, and smaller studies suggest this treatment could benefit patients.

In a previous 12-week, open-label trial, 17 patients with RA who were implanted with a VNS device on the left cervical vagus nerve saw improvement in RA symptoms, as well as a decrease in TNF production. Noninvasive devices that stimulate the auricular branch of the vagus nerve have also shown some promise. A sham-controlled study of 18 patients with systemic lupus erythematosus (SLE) found that patients who received transcutaneous auricular VNS reported reduced musculoskeletal pain over just 4 days. An open-label study of 30 patients with RA showed clinically significant reductions in disease activity score of 28 joints with C-reactive protein (DAS28-CRP) and clinical improvement in American College of Rheumatology responses over 12 weeks. Additional trials have also demonstrated this positive effect of noninvasive VNS on RA symptoms, but all studies conducted thus far have been relatively small or uncontrolled, Dr. Baker said.
 

Results of latest trial

In this new trial, published online in Arthritis & Rheumatology, researchers enrolled 113 patients with active RA who had inadequate responses or intolerance to conventional synthetic DMARDs and were naïve to biologic or targeted synthetic DMARDs. All patients were given an auricular vagus nerve stimulator via a custom-molded earpiece that was controlled by a smartphone app. Patients wore the device for 15 minutes each day. When worn and turned on, the device generated electrical signals delivered transcutaneously to the cymba concha, a region of the ear connected to the auricular branch of the vagus nerve. This stimulation is imperceptible to patients, Dr. Baker explained. “For the sham arm, we simply did not turn the device on at all,” he said. A subject in the sham arm would use the same device on a 15-minute timer, but no stimulation was given.

After 12 weeks, researchers found no statistically significant difference between the treatment and sham arms in achieving 20% improvement in ACR response criteria or mean change in DAS28-CRP. A total of 17 patients, including 12 in the treatment arm, reported adverse events during the study, and all events were categorized as mild to moderate.

While the research team was “obviously disappointed” about the results, Dr. Baker said, negative findings in trials also are important. “The real value of our study is pointing out the need for large controlled, sham-controlled studies,” he said, especially for potential treatments with a lot of enthusiasm behind them.
 

Results don’t seal the fate of other VNS approaches

“As a properly controlled trial, the results are impressively negative,” writes Roy Fleischmann, MD, clinical professor of medicine, University of Texas Southwestern Medical Center, and codirector, Metroplex Clinical Research Center, both in Dallas, in an editorial about the study. Many of the previous studies looking at this therapy in RA were open label, which could bias the results, he argued. The biggest question, he noted, is if other blinded, sham-controlled trials looking at VNS devices will show similar results.

By itself, this finding does not imply that other VNS devices will be unsuccessful, argued Jonathan Kay, MD, the Timothy S. and Elaine L. Peterson chair in rheumatology, and professor of medicine and population and quantitative health sciences, UMass Chan Medical School and UMass Memorial Medical Center, both in Worcester, Mass. He is also an investigator for the RESET-RA trial, a randomized, sham-controlled trial that will assess the safety and efficacy of an implantable VNS device in an estimated 250 patients with RA. He was not involved with Dr. Baker’s work.

“Auricular VNS is delivered more distally than cervical or splenic nerve stimulation,” Dr. Kay said, and the potential effect of these other forms of VNS may have different outcomes.

Cynthia Aranow, MD, rheumatologist and director of the Clinical Autoimmunity Center of Excellence at Feinstein Institutes for Medical Research, Manhasset, New York, agreed with Dr. Kay, noting that direct VNS stimulation via implantable device and transcutaneous stimulation through the skin are not comparable. She also is unaffiliated with the study.

“This group conducted a well-designed, sham-controlled study of a reasonable number of patients and over a reasonable period of time and observed no significant differences between those participants receiving true and those participants receiving sham stimulation,” she wrote in an email. “However, it’s important to point out that the stimulation settings used in this study were kHz (kilohertz) which is 1,000 times greater than the settings used in multiple other studies in which transauricular VNS has been shown to be clinically effective, including studies in long COVID, tinnitus, SLE, cluster headaches, erosive hand osteoarthritis, pediatric kidney disease, among others,” she said.

The role for VNS treatment, whether direct stimulation via implantable device or transcutaneous, in autoimmune and inflammatory diseases “remains to be determined by future studies,” she said.

The study was funded by Nesos. Dr. Baker received personal fees from Nesos during the study. Dr. Kay has received consulting fees from AbbVie, Boehringer Ingelheim, Celltrion Healthcare, and several other pharmaceutical companies. Dr. Aranow reports no relevant financial relationships.

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

Noninvasive auricular vagus nerve stimulation (VNS) is no more effective than placebo at controlling symptoms of rheumatoid arthritis, according to a new study. But experts emphasize that these results do not mean trials of different forms of VNS will have the same fate.

VNS offers a potential additional therapy for autoimmune disease beyond disease-modifying antirheumatic drugs, explained first author Matthew Baker, MD, clinical chief, division of immunology and rheumatology, Stanford (Calif.) University, and colleagues.

“The principle of VNS is based upon the inflammatory reflex, which describes a primitive connection between the nervous system and immune system,” the authors write. Signals sent down the vagus nerve to the splenic nerve stimulate immune cells in the spleen, which ultimately results in blocking production of inflammatory cytokines such as tumor necrosis factor. “It is hypothesized that this reduction in systemic inflammation can be harnessed for the treatment of diseases such as RA,” they continue, and smaller studies suggest this treatment could benefit patients.

In a previous 12-week, open-label trial, 17 patients with RA who were implanted with a VNS device on the left cervical vagus nerve saw improvement in RA symptoms, as well as a decrease in TNF production. Noninvasive devices that stimulate the auricular branch of the vagus nerve have also shown some promise. A sham-controlled study of 18 patients with systemic lupus erythematosus (SLE) found that patients who received transcutaneous auricular VNS reported reduced musculoskeletal pain over just 4 days. An open-label study of 30 patients with RA showed clinically significant reductions in disease activity score of 28 joints with C-reactive protein (DAS28-CRP) and clinical improvement in American College of Rheumatology responses over 12 weeks. Additional trials have also demonstrated this positive effect of noninvasive VNS on RA symptoms, but all studies conducted thus far have been relatively small or uncontrolled, Dr. Baker said.
 

Results of latest trial

In this new trial, published online in Arthritis & Rheumatology, researchers enrolled 113 patients with active RA who had inadequate responses or intolerance to conventional synthetic DMARDs and were naïve to biologic or targeted synthetic DMARDs. All patients were given an auricular vagus nerve stimulator via a custom-molded earpiece that was controlled by a smartphone app. Patients wore the device for 15 minutes each day. When worn and turned on, the device generated electrical signals delivered transcutaneously to the cymba concha, a region of the ear connected to the auricular branch of the vagus nerve. This stimulation is imperceptible to patients, Dr. Baker explained. “For the sham arm, we simply did not turn the device on at all,” he said. A subject in the sham arm would use the same device on a 15-minute timer, but no stimulation was given.

After 12 weeks, researchers found no statistically significant difference between the treatment and sham arms in achieving 20% improvement in ACR response criteria or mean change in DAS28-CRP. A total of 17 patients, including 12 in the treatment arm, reported adverse events during the study, and all events were categorized as mild to moderate.

While the research team was “obviously disappointed” about the results, Dr. Baker said, negative findings in trials also are important. “The real value of our study is pointing out the need for large controlled, sham-controlled studies,” he said, especially for potential treatments with a lot of enthusiasm behind them.
 

Results don’t seal the fate of other VNS approaches

“As a properly controlled trial, the results are impressively negative,” writes Roy Fleischmann, MD, clinical professor of medicine, University of Texas Southwestern Medical Center, and codirector, Metroplex Clinical Research Center, both in Dallas, in an editorial about the study. Many of the previous studies looking at this therapy in RA were open label, which could bias the results, he argued. The biggest question, he noted, is if other blinded, sham-controlled trials looking at VNS devices will show similar results.

By itself, this finding does not imply that other VNS devices will be unsuccessful, argued Jonathan Kay, MD, the Timothy S. and Elaine L. Peterson chair in rheumatology, and professor of medicine and population and quantitative health sciences, UMass Chan Medical School and UMass Memorial Medical Center, both in Worcester, Mass. He is also an investigator for the RESET-RA trial, a randomized, sham-controlled trial that will assess the safety and efficacy of an implantable VNS device in an estimated 250 patients with RA. He was not involved with Dr. Baker’s work.

“Auricular VNS is delivered more distally than cervical or splenic nerve stimulation,” Dr. Kay said, and the potential effect of these other forms of VNS may have different outcomes.

Cynthia Aranow, MD, rheumatologist and director of the Clinical Autoimmunity Center of Excellence at Feinstein Institutes for Medical Research, Manhasset, New York, agreed with Dr. Kay, noting that direct VNS stimulation via implantable device and transcutaneous stimulation through the skin are not comparable. She also is unaffiliated with the study.

“This group conducted a well-designed, sham-controlled study of a reasonable number of patients and over a reasonable period of time and observed no significant differences between those participants receiving true and those participants receiving sham stimulation,” she wrote in an email. “However, it’s important to point out that the stimulation settings used in this study were kHz (kilohertz) which is 1,000 times greater than the settings used in multiple other studies in which transauricular VNS has been shown to be clinically effective, including studies in long COVID, tinnitus, SLE, cluster headaches, erosive hand osteoarthritis, pediatric kidney disease, among others,” she said.

The role for VNS treatment, whether direct stimulation via implantable device or transcutaneous, in autoimmune and inflammatory diseases “remains to be determined by future studies,” she said.

The study was funded by Nesos. Dr. Baker received personal fees from Nesos during the study. Dr. Kay has received consulting fees from AbbVie, Boehringer Ingelheim, Celltrion Healthcare, and several other pharmaceutical companies. Dr. Aranow reports no relevant financial relationships.

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

Key clinical point: Risk for interstitial lung disease (ILD) was higher among patients with rheumatoid arthritis (RA) who were older, had longer disease duration, were male, were positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), and had higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels.

Major finding: The factors associated with an increased risk for RA-ILD were older age (weighted mean difference [WMD] 5.77 years; P < .00001), longer RA duration (WMD 0.80 years; P = .02), male sex (pooled odds ratio [OR] 1.92; P < .00001), positive RF (OR 1.72; P < .00001), positive ACPA (OR 1.58; P < .00001), higher ESR level (WMD 7.41 mm/h; P = .005), and higher CRP level (WMD 4.98 mg/L; P = .02).

Study details: Findings are from a systematic review and meta-analysis of 15 retrospective cohort studies and seven observational studies including 1887 patients with RA-ILD and 8066 patients with RA without ILD.

Disclosures: The authors received no specific funding for this study and declared no conflicts of interest.

Source: Zhang M et al. Factors associated with interstitial lung disease in patients with rheumatoid arthritis: A systematic review and meta-analysis. PLoS One. 2023;18(6):e0286191 (Jun 23). Doi: 10.1371/journal.pone.0286191

Key clinical point: Risk for interstitial lung disease (ILD) was higher among patients with rheumatoid arthritis (RA) who were older, had longer disease duration, were male, were positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), and had higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels.

Major finding: The factors associated with an increased risk for RA-ILD were older age (weighted mean difference [WMD] 5.77 years; P < .00001), longer RA duration (WMD 0.80 years; P = .02), male sex (pooled odds ratio [OR] 1.92; P < .00001), positive RF (OR 1.72; P < .00001), positive ACPA (OR 1.58; P < .00001), higher ESR level (WMD 7.41 mm/h; P = .005), and higher CRP level (WMD 4.98 mg/L; P = .02).

Study details: Findings are from a systematic review and meta-analysis of 15 retrospective cohort studies and seven observational studies including 1887 patients with RA-ILD and 8066 patients with RA without ILD.

Disclosures: The authors received no specific funding for this study and declared no conflicts of interest.

Source: Zhang M et al. Factors associated with interstitial lung disease in patients with rheumatoid arthritis: A systematic review and meta-analysis. PLoS One. 2023;18(6):e0286191 (Jun 23). Doi: 10.1371/journal.pone.0286191

Key clinical point: Risk for interstitial lung disease (ILD) was higher among patients with rheumatoid arthritis (RA) who were older, had longer disease duration, were male, were positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), and had higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels.

Major finding: The factors associated with an increased risk for RA-ILD were older age (weighted mean difference [WMD] 5.77 years; P < .00001), longer RA duration (WMD 0.80 years; P = .02), male sex (pooled odds ratio [OR] 1.92; P < .00001), positive RF (OR 1.72; P < .00001), positive ACPA (OR 1.58; P < .00001), higher ESR level (WMD 7.41 mm/h; P = .005), and higher CRP level (WMD 4.98 mg/L; P = .02).

Study details: Findings are from a systematic review and meta-analysis of 15 retrospective cohort studies and seven observational studies including 1887 patients with RA-ILD and 8066 patients with RA without ILD.

Disclosures: The authors received no specific funding for this study and declared no conflicts of interest.

Source: Zhang M et al. Factors associated with interstitial lung disease in patients with rheumatoid arthritis: A systematic review and meta-analysis. PLoS One. 2023;18(6):e0286191 (Jun 23). Doi: 10.1371/journal.pone.0286191

Key clinical point: Interleukin-6 receptor inhibitors (IL-6Ri) effectively increased hemoglobin levels in patients with rheumatoid arthritis (RA) irrespective of their baseline levels, whereas Janus-kinase inhibitors (JAKi) improved hemoglobin levels in patients with RA and anemia and retained or decreased in those without anemia.

Major finding: From baseline to the 12-month follow-up, IL-6Ri increased hemoglobin levels in all patients with RA, irrespective of whether their baseline hemoglobin levels were low, intermediate, or high, and JAKi increased hemoglobin levels in those with RA and anemia, with levels remaining unaltered in those with intermediate hemoglobin levels and decreasing in those without anemia (all P < .001).

Study details: This study evaluated 2093 patients with RA from the ANSWER cohort who received biologic or targeted-synthetic disease-modifying antirheumatic drugs.

Disclosures: The ANSWER cohort study was supported by grants from 10 pharmaceutical companies, including AbbVie G.K., Asahi-Kasei Pharma, AYUMI Pharmaceutical Co., and others, and an information technology services company. Several authors declared receiving speaker fees, consulting fees, honoraria, or research grants from various sources.

Source: Nakayama Y et al. IL-6 inhibitors and JAK inhibitors as favourable treatment options for patients with anaemia and rheumatoid arthritis: ANSWER cohort study. Rheumatology (Oxford). 2023 (Jun 24). Doi: 10.1093/rheumatology/kead299

Key clinical point: Interleukin-6 receptor inhibitors (IL-6Ri) effectively increased hemoglobin levels in patients with rheumatoid arthritis (RA) irrespective of their baseline levels, whereas Janus-kinase inhibitors (JAKi) improved hemoglobin levels in patients with RA and anemia and retained or decreased in those without anemia.

Major finding: From baseline to the 12-month follow-up, IL-6Ri increased hemoglobin levels in all patients with RA, irrespective of whether their baseline hemoglobin levels were low, intermediate, or high, and JAKi increased hemoglobin levels in those with RA and anemia, with levels remaining unaltered in those with intermediate hemoglobin levels and decreasing in those without anemia (all P < .001).

Study details: This study evaluated 2093 patients with RA from the ANSWER cohort who received biologic or targeted-synthetic disease-modifying antirheumatic drugs.

Disclosures: The ANSWER cohort study was supported by grants from 10 pharmaceutical companies, including AbbVie G.K., Asahi-Kasei Pharma, AYUMI Pharmaceutical Co., and others, and an information technology services company. Several authors declared receiving speaker fees, consulting fees, honoraria, or research grants from various sources.

Source: Nakayama Y et al. IL-6 inhibitors and JAK inhibitors as favourable treatment options for patients with anaemia and rheumatoid arthritis: ANSWER cohort study. Rheumatology (Oxford). 2023 (Jun 24). Doi: 10.1093/rheumatology/kead299

Key clinical point: Interleukin-6 receptor inhibitors (IL-6Ri) effectively increased hemoglobin levels in patients with rheumatoid arthritis (RA) irrespective of their baseline levels, whereas Janus-kinase inhibitors (JAKi) improved hemoglobin levels in patients with RA and anemia and retained or decreased in those without anemia.

Major finding: From baseline to the 12-month follow-up, IL-6Ri increased hemoglobin levels in all patients with RA, irrespective of whether their baseline hemoglobin levels were low, intermediate, or high, and JAKi increased hemoglobin levels in those with RA and anemia, with levels remaining unaltered in those with intermediate hemoglobin levels and decreasing in those without anemia (all P < .001).

Study details: This study evaluated 2093 patients with RA from the ANSWER cohort who received biologic or targeted-synthetic disease-modifying antirheumatic drugs.

Disclosures: The ANSWER cohort study was supported by grants from 10 pharmaceutical companies, including AbbVie G.K., Asahi-Kasei Pharma, AYUMI Pharmaceutical Co., and others, and an information technology services company. Several authors declared receiving speaker fees, consulting fees, honoraria, or research grants from various sources.

Source: Nakayama Y et al. IL-6 inhibitors and JAK inhibitors as favourable treatment options for patients with anaemia and rheumatoid arthritis: ANSWER cohort study. Rheumatology (Oxford). 2023 (Jun 24). Doi: 10.1093/rheumatology/kead299

Key clinical point: Higher adherence to the Mediterranean diet may help reduce disease impact, disease activity, and functional disability in patients with rheumatoid arthritis (RA).

Major finding: Patients with high vs low adherence to the Mediterranean diet had significantly lower Disease Activity Score of 28 Joints calculated with C-reactive protein (median 2.29 vs 3.27; P = .038), Health Assessment Questionnaire score (median 0.56 vs 1.00; P = .027), and Rheumatoid Arthritis Impact of Disease questionnaire score (median 3.51 vs 5.65; P = .032).

Study details: Findings are from a cross-sectional observational study including 120 patients with RA.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Charneca S et al. The Mediterranean diet, and not dietary inflammatory index, is associated with rheumatoid arthritis disease activity, the impact of disease and functional disability. Eur J Nutr. 2023 (Jun 24). Doi: 10.1007/s00394-023-03196-8

Key clinical point: Higher adherence to the Mediterranean diet may help reduce disease impact, disease activity, and functional disability in patients with rheumatoid arthritis (RA).

Major finding: Patients with high vs low adherence to the Mediterranean diet had significantly lower Disease Activity Score of 28 Joints calculated with C-reactive protein (median 2.29 vs 3.27; P = .038), Health Assessment Questionnaire score (median 0.56 vs 1.00; P = .027), and Rheumatoid Arthritis Impact of Disease questionnaire score (median 3.51 vs 5.65; P = .032).

Study details: Findings are from a cross-sectional observational study including 120 patients with RA.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Charneca S et al. The Mediterranean diet, and not dietary inflammatory index, is associated with rheumatoid arthritis disease activity, the impact of disease and functional disability. Eur J Nutr. 2023 (Jun 24). Doi: 10.1007/s00394-023-03196-8

Key clinical point: Higher adherence to the Mediterranean diet may help reduce disease impact, disease activity, and functional disability in patients with rheumatoid arthritis (RA).

Major finding: Patients with high vs low adherence to the Mediterranean diet had significantly lower Disease Activity Score of 28 Joints calculated with C-reactive protein (median 2.29 vs 3.27; P = .038), Health Assessment Questionnaire score (median 0.56 vs 1.00; P = .027), and Rheumatoid Arthritis Impact of Disease questionnaire score (median 3.51 vs 5.65; P = .032).

Study details: Findings are from a cross-sectional observational study including 120 patients with RA.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Charneca S et al. The Mediterranean diet, and not dietary inflammatory index, is associated with rheumatoid arthritis disease activity, the impact of disease and functional disability. Eur J Nutr. 2023 (Jun 24). Doi: 10.1007/s00394-023-03196-8

Key clinical point: Concomitant interstitial lung disease (ILD) is a significant factor associated with failure to achieve clinical remission and an increased risk for unfavorable clinical events in patients with rheumatoid arthritis (RA).

Major finding: The presence of ILD was significantly associated with failure to achieve Disease Activity Score in 28 Joints remission (adjusted hazard ratio [aHR] 0.71; P = .002) and increased risk for death (aHR 3.24; P < .001), hospitalized infections (aHR 2.60; P < .001), major adverse cardiac events (aHR 3.40; P < .001), and lung cancer (aHR 16.0; P < .001).

Study details: This study analyzed the data of 1522 patients with RA (ILD group n = 287; non-ILD group n = 1235) from the observational IORRA cohort.

Disclosures: This study was supported by the Ministry of Health, Labour, and Welfare of Japan and other sources. Some authors declared serving as consultants for or receiving research grants, research funding, or lecture, speaker, or consulting fees from various sources.

Source: Sugano E et al. Impact of interstitial lung disease on clinical remission and unfavourable events of rheumatoid arthritis: Results from the IORRA cohort. Rheumatology (Oxford). 2023 (Jun 28). Doi: 10.1093/rheumatology/kead317

Key clinical point: Concomitant interstitial lung disease (ILD) is a significant factor associated with failure to achieve clinical remission and an increased risk for unfavorable clinical events in patients with rheumatoid arthritis (RA).

Major finding: The presence of ILD was significantly associated with failure to achieve Disease Activity Score in 28 Joints remission (adjusted hazard ratio [aHR] 0.71; P = .002) and increased risk for death (aHR 3.24; P < .001), hospitalized infections (aHR 2.60; P < .001), major adverse cardiac events (aHR 3.40; P < .001), and lung cancer (aHR 16.0; P < .001).

Study details: This study analyzed the data of 1522 patients with RA (ILD group n = 287; non-ILD group n = 1235) from the observational IORRA cohort.

Disclosures: This study was supported by the Ministry of Health, Labour, and Welfare of Japan and other sources. Some authors declared serving as consultants for or receiving research grants, research funding, or lecture, speaker, or consulting fees from various sources.

Source: Sugano E et al. Impact of interstitial lung disease on clinical remission and unfavourable events of rheumatoid arthritis: Results from the IORRA cohort. Rheumatology (Oxford). 2023 (Jun 28). Doi: 10.1093/rheumatology/kead317

Key clinical point: Concomitant interstitial lung disease (ILD) is a significant factor associated with failure to achieve clinical remission and an increased risk for unfavorable clinical events in patients with rheumatoid arthritis (RA).

Major finding: The presence of ILD was significantly associated with failure to achieve Disease Activity Score in 28 Joints remission (adjusted hazard ratio [aHR] 0.71; P = .002) and increased risk for death (aHR 3.24; P < .001), hospitalized infections (aHR 2.60; P < .001), major adverse cardiac events (aHR 3.40; P < .001), and lung cancer (aHR 16.0; P < .001).

Study details: This study analyzed the data of 1522 patients with RA (ILD group n = 287; non-ILD group n = 1235) from the observational IORRA cohort.

Disclosures: This study was supported by the Ministry of Health, Labour, and Welfare of Japan and other sources. Some authors declared serving as consultants for or receiving research grants, research funding, or lecture, speaker, or consulting fees from various sources.

Source: Sugano E et al. Impact of interstitial lung disease on clinical remission and unfavourable events of rheumatoid arthritis: Results from the IORRA cohort. Rheumatology (Oxford). 2023 (Jun 28). Doi: 10.1093/rheumatology/kead317

Key clinical point: Exposure to volatile organic compounds (VOC) significantly increased the risk for rheumatoid arthritis (RA), highlighting environmental pollutants as a risk factor for RA.

Major finding: Patients with RA had a significantly higher urine concentration of seven VOC than those without arthritis (all P < .05). The risk for RA was significantly higher among those in the highest vs lowest concentration quantile of AMCC (adjusted odds ratio [aOR] 2.173; 95% CI 1.021-4.627) and 3HPMA (aOR 2.663; 95% CI 1.288-5.508), with the parent compounds being N,N-Dimethylformamide and acrolein, respectively.

Study details: This cross-sectional study included 9536 participants with complete information on 15 urine VOC, of whom 618 participants had RA and 8918 did not have arthritis.

Disclosures: This study was supported by the Fundamental Research Funds for the Central Universities of Central South University, the National Natural Science Foundation of China, and other sources. The authors declared no conflicts of interest.

Source: Lei T et al. The exposure to volatile organic chemicals associates positively with rheumatoid arthritis: A cross-sectional study from the NHANES program. Front Immunol. 2023;14:1098683 (Jun 19). Doi: 10.3389/fimmu.2023.1098683

Key clinical point: Exposure to volatile organic compounds (VOC) significantly increased the risk for rheumatoid arthritis (RA), highlighting environmental pollutants as a risk factor for RA.

Major finding: Patients with RA had a significantly higher urine concentration of seven VOC than those without arthritis (all P < .05). The risk for RA was significantly higher among those in the highest vs lowest concentration quantile of AMCC (adjusted odds ratio [aOR] 2.173; 95% CI 1.021-4.627) and 3HPMA (aOR 2.663; 95% CI 1.288-5.508), with the parent compounds being N,N-Dimethylformamide and acrolein, respectively.

Study details: This cross-sectional study included 9536 participants with complete information on 15 urine VOC, of whom 618 participants had RA and 8918 did not have arthritis.

Disclosures: This study was supported by the Fundamental Research Funds for the Central Universities of Central South University, the National Natural Science Foundation of China, and other sources. The authors declared no conflicts of interest.

Source: Lei T et al. The exposure to volatile organic chemicals associates positively with rheumatoid arthritis: A cross-sectional study from the NHANES program. Front Immunol. 2023;14:1098683 (Jun 19). Doi: 10.3389/fimmu.2023.1098683

Key clinical point: Exposure to volatile organic compounds (VOC) significantly increased the risk for rheumatoid arthritis (RA), highlighting environmental pollutants as a risk factor for RA.

Major finding: Patients with RA had a significantly higher urine concentration of seven VOC than those without arthritis (all P < .05). The risk for RA was significantly higher among those in the highest vs lowest concentration quantile of AMCC (adjusted odds ratio [aOR] 2.173; 95% CI 1.021-4.627) and 3HPMA (aOR 2.663; 95% CI 1.288-5.508), with the parent compounds being N,N-Dimethylformamide and acrolein, respectively.

Study details: This cross-sectional study included 9536 participants with complete information on 15 urine VOC, of whom 618 participants had RA and 8918 did not have arthritis.

Disclosures: This study was supported by the Fundamental Research Funds for the Central Universities of Central South University, the National Natural Science Foundation of China, and other sources. The authors declared no conflicts of interest.

Source: Lei T et al. The exposure to volatile organic chemicals associates positively with rheumatoid arthritis: A cross-sectional study from the NHANES program. Front Immunol. 2023;14:1098683 (Jun 19). Doi: 10.3389/fimmu.2023.1098683

Key clinical point: In patients with established rheumatoid arthritis (RA) age ≥ 65 years, an add-on low-dose prednisolone administration for 2 years led to a marginal weight gain, which appeared mostly as a beneficial increase in lean mass.

Major finding: At 2 years, the body weight increased slightly with 5 mg/day prednisolone (mean change +0.9 kg; 95% CI 0.3-1.6 kg), whereas there was a non-significant decrease with placebo (between-treatment difference 1.3 kg; P < .01). The change in body weight with prednisolone was mostly due to increased lean mass rather than fat mass and was not significantly related to disease activity.

Study details: This substudy of the phase 4 GLORIA trial included 449 patients aged ≥65 years with active RA who were randomly assigned to receive placebo (n = 225) or 5 mg/day prednisolone (n = 224) along with standard care for 2 years.

Disclosures: The GLORIA study was funded by the European Union’s Horizon 2020 research and innovation program. M Boers and MR Kok declared ties with various sources. The other authors declared no competing interests.

Source: Güler-Yüksel M et al. Changes in body weight and body composition in patients with active rheumatoid arthritis aged 65+ treated with 2-year low-dose add-on prednisolone in the randomised double-blind placebo-controlled GLORIA trial. RMD Open. 2023;9:e002905 (Jun 22). Doi: 10.1136/rmdopen-2022-002905

Key clinical point: In patients with established rheumatoid arthritis (RA) age ≥ 65 years, an add-on low-dose prednisolone administration for 2 years led to a marginal weight gain, which appeared mostly as a beneficial increase in lean mass.

Major finding: At 2 years, the body weight increased slightly with 5 mg/day prednisolone (mean change +0.9 kg; 95% CI 0.3-1.6 kg), whereas there was a non-significant decrease with placebo (between-treatment difference 1.3 kg; P < .01). The change in body weight with prednisolone was mostly due to increased lean mass rather than fat mass and was not significantly related to disease activity.

Study details: This substudy of the phase 4 GLORIA trial included 449 patients aged ≥65 years with active RA who were randomly assigned to receive placebo (n = 225) or 5 mg/day prednisolone (n = 224) along with standard care for 2 years.

Disclosures: The GLORIA study was funded by the European Union’s Horizon 2020 research and innovation program. M Boers and MR Kok declared ties with various sources. The other authors declared no competing interests.

Source: Güler-Yüksel M et al. Changes in body weight and body composition in patients with active rheumatoid arthritis aged 65+ treated with 2-year low-dose add-on prednisolone in the randomised double-blind placebo-controlled GLORIA trial. RMD Open. 2023;9:e002905 (Jun 22). Doi: 10.1136/rmdopen-2022-002905

Key clinical point: In patients with established rheumatoid arthritis (RA) age ≥ 65 years, an add-on low-dose prednisolone administration for 2 years led to a marginal weight gain, which appeared mostly as a beneficial increase in lean mass.

Major finding: At 2 years, the body weight increased slightly with 5 mg/day prednisolone (mean change +0.9 kg; 95% CI 0.3-1.6 kg), whereas there was a non-significant decrease with placebo (between-treatment difference 1.3 kg; P < .01). The change in body weight with prednisolone was mostly due to increased lean mass rather than fat mass and was not significantly related to disease activity.

Study details: This substudy of the phase 4 GLORIA trial included 449 patients aged ≥65 years with active RA who were randomly assigned to receive placebo (n = 225) or 5 mg/day prednisolone (n = 224) along with standard care for 2 years.

Disclosures: The GLORIA study was funded by the European Union’s Horizon 2020 research and innovation program. M Boers and MR Kok declared ties with various sources. The other authors declared no competing interests.

Source: Güler-Yüksel M et al. Changes in body weight and body composition in patients with active rheumatoid arthritis aged 65+ treated with 2-year low-dose add-on prednisolone in the randomised double-blind placebo-controlled GLORIA trial. RMD Open. 2023;9:e002905 (Jun 22). Doi: 10.1136/rmdopen-2022-002905

Key clinical point: A substantial proportion of patients with early rheumatoid arthritis (RA) had unacceptably high levels of pain with or without low inflammation at 2 years after diagnosis, with joint tenderness at the 3-month follow-up predicting long-term pain despite low inflammation.

Major finding: Nearly one third of patients with early RA had unacceptable pain levels after 2 years of follow-up, with almost 80% of them also having low inflammation. At the 3-month follow-up, the difference between tender and swollen joint counts predicted the 2-year risk for unacceptable pain (odds ratio [OR] 2.00; P < .05) and unacceptable pain with low inflammation (OR 2.02; P < .05).

Study details: Findings are from a retrospective study including 275 patients with early RA.

Disclosures: This study was supported by The Swedish Research Council, The Swedish Rheumatism Association, and Lund University. Some authors declared working as a medical solution lead in rheumatology or receiving consulting fees, speaking fees, and unrestricted grant from various sources. Three authors declared no conflicts of interest.

Source: Eberhard A et al. Joint tenderness at 3 months follow-up better predicts long-term pain than baseline characteristics in early rheumatoid arthritis patients. Rheumatology (Oxford). 2023 (Jun 14). Doi: 10.1093/rheumatology/kead278

Key clinical point: A substantial proportion of patients with early rheumatoid arthritis (RA) had unacceptably high levels of pain with or without low inflammation at 2 years after diagnosis, with joint tenderness at the 3-month follow-up predicting long-term pain despite low inflammation.

Major finding: Nearly one third of patients with early RA had unacceptable pain levels after 2 years of follow-up, with almost 80% of them also having low inflammation. At the 3-month follow-up, the difference between tender and swollen joint counts predicted the 2-year risk for unacceptable pain (odds ratio [OR] 2.00; P < .05) and unacceptable pain with low inflammation (OR 2.02; P < .05).

Study details: Findings are from a retrospective study including 275 patients with early RA.

Disclosures: This study was supported by The Swedish Research Council, The Swedish Rheumatism Association, and Lund University. Some authors declared working as a medical solution lead in rheumatology or receiving consulting fees, speaking fees, and unrestricted grant from various sources. Three authors declared no conflicts of interest.

Source: Eberhard A et al. Joint tenderness at 3 months follow-up better predicts long-term pain than baseline characteristics in early rheumatoid arthritis patients. Rheumatology (Oxford). 2023 (Jun 14). Doi: 10.1093/rheumatology/kead278

Key clinical point: A substantial proportion of patients with early rheumatoid arthritis (RA) had unacceptably high levels of pain with or without low inflammation at 2 years after diagnosis, with joint tenderness at the 3-month follow-up predicting long-term pain despite low inflammation.

Major finding: Nearly one third of patients with early RA had unacceptable pain levels after 2 years of follow-up, with almost 80% of them also having low inflammation. At the 3-month follow-up, the difference between tender and swollen joint counts predicted the 2-year risk for unacceptable pain (odds ratio [OR] 2.00; P < .05) and unacceptable pain with low inflammation (OR 2.02; P < .05).

Study details: Findings are from a retrospective study including 275 patients with early RA.

Disclosures: This study was supported by The Swedish Research Council, The Swedish Rheumatism Association, and Lund University. Some authors declared working as a medical solution lead in rheumatology or receiving consulting fees, speaking fees, and unrestricted grant from various sources. Three authors declared no conflicts of interest.

Source: Eberhard A et al. Joint tenderness at 3 months follow-up better predicts long-term pain than baseline characteristics in early rheumatoid arthritis patients. Rheumatology (Oxford). 2023 (Jun 14). Doi: 10.1093/rheumatology/kead278