Rheumatoid Arthritis

A blood test that uses a patient’s unique genetic signature has shown some ability to predict nonresponse to tumor necrosis factor inhibitors as treatment for rheumatoid arthritis, an observational clinical study has found, but the test’s predictive accuracy was well below 100%.

The test is the blood-based molecular signature response classifier (MSRC) that uses RNA sequencing data based on 23 different biomarkers: 19 RNA transcripts and 4 clinical features. The clinical features are body mass index, gender, patient global assessment, and anticyclic citrullinated protein (anti-CCP) status.

The NETWORK-004 study, published in Rheumatology and Therapy, was able to stratify patients who were likely to respond inadequately to TNFi therapy and could provide patient-specific information to guide therapy choice in RA patients regardless of whether they’ve already been on TNFi therapy. The study evaluated the MSRC test in 504 patients, 391 of whom were treatment naive.
 

Avoiding ‘fail first’ approach

The idea behind the test is to circumvent the “fail first” approach in finding the right therapy for RA in an individual patient. While the test costs $4,995, Alif Saleh, chief executive officer of Scipher Medicine, which markets the test under the name PrismRA, said in a press release that it has the potential to reduce costs by $19,000 or more per patient per year by avoiding treatments that don’t work. A previous study, which Scipher funded, reported that the test resulted in savings of $7,379 in per-patient costs of ineffective therapy. The same study reported a 25% decrease in costs for ineffective treatments for Medicare-eligible patients.

The price of RA drugs, particularly anti-TNF agents, is hefty and rising. GoodRx has reported that the price of RA drugs increased 92% from 2014 to 2019, and the prices for anti-TNF agents such as etanercept and adalimumab more than doubled in that period. Adalimumab can cost upwards of $84,000 per year while etanercept has a list price of around $72,000 a year. The pharmacy benefit manager WellDyne started covering the test MSRC in February.

Nehad Soloman, MD, a rheumatologist and internist at Midwestern University Arizona College of Osteopathic Medicine in Glendale and a compensated NETWORK-004 investigator, said the MSRC test would be indicated for confirmed RA patients for whom rheumatologists are considering biologic agents, particularly TNFi drugs. “You wouldn’t do it on an RA patient who’s been on several different medications because it doesn’t serve a purpose at that point,” he said.

The potential cost savings may not be the only reason to use the test, Dr. Soloman said. “You don’t want to be dabbling with the wrong drug if there’s another path you can try and save society some money as well as the time and energy it takes to monitor the patients – as well as the patient’s pain,” he said.
 

How the MSRC test works

The MSRC test detects a signal that’s associated with a high or very high likelihood of inadequate response to TNFi therapies and indicates that the patient is unlikely to achieve low disease activity or remission with TNFi therapies. Response is defined as achieving ACR50 – meaning 50% improvement in American College of Rheumatology response criteria – at 6 months.

Test results are reported on a continuous 1-25 scale, explained Slava Akmaev, PhD, chief technology officer and head of therapeutics at Scipher. “The higher the score, the more likely the patient will have an inadequate response to TNFi therapies and be unable to reach low disease activity; the lower the score, the less likely the patient will have an inadequate response to TNFi therapies,” he said. However, Dr. Akmaev noted that a low score does not ensure a positive response to TNFi therapies.

The MSRC test differs from the multibiomarker disease activity blood test (MBDA; marketed as Vectra by Myriad Genetics) in the number of biomarkers it measures: 19 RNA transcripts vs. 12 serum protein biomarkers in MBDA. The MBDA test is also intended to provide a quantitative, objective measurement of RA disease activity rather than to predict nonresponse to TNFi or other biologics. A number of studies have validated the MBDA test for predicting disease control in RA patients, but not necessarily response to TNFi therapy.

The “high” category threshold of the MSRC test corresponds to an approximate 90% chance of inadequate response to TNFi therapy, or a 10% chance of responding. The “very high” category threshold corresponds to an approximate 95% chance of inadequate response to TNFi therapy, Dr. Akmaev said.

NETWORK-004 used area under the curve (AUC) to measure the accuracy of the MSRC test. An AUC of 1 represents 100% accuracy. Overall, the MSRC had an AUC of 0.64, or 64% accuracy of predicting patients unlikely to respond to TNFi therapy and to achieve ACR50 at 6 months, with an odds ratio of 4.1 (95% confidence interval, 2.0-8.3; P = .0001).

The predictive accuracy went up to 74% with ORs of 3.4-8.8 for additional endpoints at 3 and 6 months (P < .01). Among patients who had already been on TNFi therapy, the predictive accuracy was 83% and associated with ORs of 3.3-26.6 based on ACR, 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), and Clinical Disease Activity Index (CDAI) metrics.

The investigators also performed an in-cohort cross-validation of the MSRC using baseline blood samples of 245 treatment-naive patients from the CERTAIN study, which yielded a 66% predictive accuracy for the ACR50 outcome at 6 months. Using the 19 RNA transcripts from the test, but not the clinical factors, the predictive accuracy was 62.5%. Using ACR70, CDAI, and DAS28 as measures for 6-month response, the cross-validation analysis of all 23 MSRC features yielded predictive accuracy of 64%-67%.

The study found significant differences in model scores between patients who did and did not have the molecular signal of nonresponse, and the proportion of patients who achieved low disease activity or remission at 6 months based on CDAI and DAS28-CRP measures was greater among those who lacked a molecular signature of nonresponse.

“Those who lack this signature can proceed with TNFi therapy and possibly achieve an increased response rate relative to the unstratified population,” wrote lead study author Stanley B. Cohen, MD, and colleagues.

Daniel E. Furst, MD, emeritus professor at the University of California, Los Angeles, described the design of the NETWORK-004 study as “excellent,” but said that it didn’t overcome potential issues with the MSRC test itself. “The results unfortunately are great for group data but not for individuals, with a predictive area under the curve of 60% to 80%, it really is not that useful,” he said. “Let’s say you’re a patient who’s not doing well, and I do a test and it’s positive; that still means that 20% of the time you will respond.”

He also noted that he coauthored a paper that used decreases in DAS28 to predict nonresponse to certolizumab pegol plus methotrexate with 95% probability in the first 12 weeks of treatment. “That’s closer to what we need,” Dr. Furst said.

However, the MSRC test is a promising sign of where testing for predicting RA therapy is headed, he said. “We are steadily working toward genetic signatures that really are predictive on an individual basis,” Dr. Furst said. “It’s coming; it’s just not here yet.”

Dr. Furst had no relevant financial relationships to disclose. Dr. Soloman is a paid investigator and consultant to Scipher Medicine.
 

A blood test that uses a patient’s unique genetic signature has shown some ability to predict nonresponse to tumor necrosis factor inhibitors as treatment for rheumatoid arthritis, an observational clinical study has found, but the test’s predictive accuracy was well below 100%.

The test is the blood-based molecular signature response classifier (MSRC) that uses RNA sequencing data based on 23 different biomarkers: 19 RNA transcripts and 4 clinical features. The clinical features are body mass index, gender, patient global assessment, and anticyclic citrullinated protein (anti-CCP) status.

The NETWORK-004 study, published in Rheumatology and Therapy, was able to stratify patients who were likely to respond inadequately to TNFi therapy and could provide patient-specific information to guide therapy choice in RA patients regardless of whether they’ve already been on TNFi therapy. The study evaluated the MSRC test in 504 patients, 391 of whom were treatment naive.
 

Avoiding ‘fail first’ approach

The idea behind the test is to circumvent the “fail first” approach in finding the right therapy for RA in an individual patient. While the test costs $4,995, Alif Saleh, chief executive officer of Scipher Medicine, which markets the test under the name PrismRA, said in a press release that it has the potential to reduce costs by $19,000 or more per patient per year by avoiding treatments that don’t work. A previous study, which Scipher funded, reported that the test resulted in savings of $7,379 in per-patient costs of ineffective therapy. The same study reported a 25% decrease in costs for ineffective treatments for Medicare-eligible patients.

The price of RA drugs, particularly anti-TNF agents, is hefty and rising. GoodRx has reported that the price of RA drugs increased 92% from 2014 to 2019, and the prices for anti-TNF agents such as etanercept and adalimumab more than doubled in that period. Adalimumab can cost upwards of $84,000 per year while etanercept has a list price of around $72,000 a year. The pharmacy benefit manager WellDyne started covering the test MSRC in February.

Nehad Soloman, MD, a rheumatologist and internist at Midwestern University Arizona College of Osteopathic Medicine in Glendale and a compensated NETWORK-004 investigator, said the MSRC test would be indicated for confirmed RA patients for whom rheumatologists are considering biologic agents, particularly TNFi drugs. “You wouldn’t do it on an RA patient who’s been on several different medications because it doesn’t serve a purpose at that point,” he said.

The potential cost savings may not be the only reason to use the test, Dr. Soloman said. “You don’t want to be dabbling with the wrong drug if there’s another path you can try and save society some money as well as the time and energy it takes to monitor the patients – as well as the patient’s pain,” he said.
 

How the MSRC test works

The MSRC test detects a signal that’s associated with a high or very high likelihood of inadequate response to TNFi therapies and indicates that the patient is unlikely to achieve low disease activity or remission with TNFi therapies. Response is defined as achieving ACR50 – meaning 50% improvement in American College of Rheumatology response criteria – at 6 months.

Test results are reported on a continuous 1-25 scale, explained Slava Akmaev, PhD, chief technology officer and head of therapeutics at Scipher. “The higher the score, the more likely the patient will have an inadequate response to TNFi therapies and be unable to reach low disease activity; the lower the score, the less likely the patient will have an inadequate response to TNFi therapies,” he said. However, Dr. Akmaev noted that a low score does not ensure a positive response to TNFi therapies.

The MSRC test differs from the multibiomarker disease activity blood test (MBDA; marketed as Vectra by Myriad Genetics) in the number of biomarkers it measures: 19 RNA transcripts vs. 12 serum protein biomarkers in MBDA. The MBDA test is also intended to provide a quantitative, objective measurement of RA disease activity rather than to predict nonresponse to TNFi or other biologics. A number of studies have validated the MBDA test for predicting disease control in RA patients, but not necessarily response to TNFi therapy.

The “high” category threshold of the MSRC test corresponds to an approximate 90% chance of inadequate response to TNFi therapy, or a 10% chance of responding. The “very high” category threshold corresponds to an approximate 95% chance of inadequate response to TNFi therapy, Dr. Akmaev said.

NETWORK-004 used area under the curve (AUC) to measure the accuracy of the MSRC test. An AUC of 1 represents 100% accuracy. Overall, the MSRC had an AUC of 0.64, or 64% accuracy of predicting patients unlikely to respond to TNFi therapy and to achieve ACR50 at 6 months, with an odds ratio of 4.1 (95% confidence interval, 2.0-8.3; P = .0001).

The predictive accuracy went up to 74% with ORs of 3.4-8.8 for additional endpoints at 3 and 6 months (P < .01). Among patients who had already been on TNFi therapy, the predictive accuracy was 83% and associated with ORs of 3.3-26.6 based on ACR, 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), and Clinical Disease Activity Index (CDAI) metrics.

The investigators also performed an in-cohort cross-validation of the MSRC using baseline blood samples of 245 treatment-naive patients from the CERTAIN study, which yielded a 66% predictive accuracy for the ACR50 outcome at 6 months. Using the 19 RNA transcripts from the test, but not the clinical factors, the predictive accuracy was 62.5%. Using ACR70, CDAI, and DAS28 as measures for 6-month response, the cross-validation analysis of all 23 MSRC features yielded predictive accuracy of 64%-67%.

The study found significant differences in model scores between patients who did and did not have the molecular signal of nonresponse, and the proportion of patients who achieved low disease activity or remission at 6 months based on CDAI and DAS28-CRP measures was greater among those who lacked a molecular signature of nonresponse.

“Those who lack this signature can proceed with TNFi therapy and possibly achieve an increased response rate relative to the unstratified population,” wrote lead study author Stanley B. Cohen, MD, and colleagues.

Daniel E. Furst, MD, emeritus professor at the University of California, Los Angeles, described the design of the NETWORK-004 study as “excellent,” but said that it didn’t overcome potential issues with the MSRC test itself. “The results unfortunately are great for group data but not for individuals, with a predictive area under the curve of 60% to 80%, it really is not that useful,” he said. “Let’s say you’re a patient who’s not doing well, and I do a test and it’s positive; that still means that 20% of the time you will respond.”

He also noted that he coauthored a paper that used decreases in DAS28 to predict nonresponse to certolizumab pegol plus methotrexate with 95% probability in the first 12 weeks of treatment. “That’s closer to what we need,” Dr. Furst said.

However, the MSRC test is a promising sign of where testing for predicting RA therapy is headed, he said. “We are steadily working toward genetic signatures that really are predictive on an individual basis,” Dr. Furst said. “It’s coming; it’s just not here yet.”

Dr. Furst had no relevant financial relationships to disclose. Dr. Soloman is a paid investigator and consultant to Scipher Medicine.
 

A blood test that uses a patient’s unique genetic signature has shown some ability to predict nonresponse to tumor necrosis factor inhibitors as treatment for rheumatoid arthritis, an observational clinical study has found, but the test’s predictive accuracy was well below 100%.

The test is the blood-based molecular signature response classifier (MSRC) that uses RNA sequencing data based on 23 different biomarkers: 19 RNA transcripts and 4 clinical features. The clinical features are body mass index, gender, patient global assessment, and anticyclic citrullinated protein (anti-CCP) status.

The NETWORK-004 study, published in Rheumatology and Therapy, was able to stratify patients who were likely to respond inadequately to TNFi therapy and could provide patient-specific information to guide therapy choice in RA patients regardless of whether they’ve already been on TNFi therapy. The study evaluated the MSRC test in 504 patients, 391 of whom were treatment naive.
 

Avoiding ‘fail first’ approach

The idea behind the test is to circumvent the “fail first” approach in finding the right therapy for RA in an individual patient. While the test costs $4,995, Alif Saleh, chief executive officer of Scipher Medicine, which markets the test under the name PrismRA, said in a press release that it has the potential to reduce costs by $19,000 or more per patient per year by avoiding treatments that don’t work. A previous study, which Scipher funded, reported that the test resulted in savings of $7,379 in per-patient costs of ineffective therapy. The same study reported a 25% decrease in costs for ineffective treatments for Medicare-eligible patients.

The price of RA drugs, particularly anti-TNF agents, is hefty and rising. GoodRx has reported that the price of RA drugs increased 92% from 2014 to 2019, and the prices for anti-TNF agents such as etanercept and adalimumab more than doubled in that period. Adalimumab can cost upwards of $84,000 per year while etanercept has a list price of around $72,000 a year. The pharmacy benefit manager WellDyne started covering the test MSRC in February.

Nehad Soloman, MD, a rheumatologist and internist at Midwestern University Arizona College of Osteopathic Medicine in Glendale and a compensated NETWORK-004 investigator, said the MSRC test would be indicated for confirmed RA patients for whom rheumatologists are considering biologic agents, particularly TNFi drugs. “You wouldn’t do it on an RA patient who’s been on several different medications because it doesn’t serve a purpose at that point,” he said.

The potential cost savings may not be the only reason to use the test, Dr. Soloman said. “You don’t want to be dabbling with the wrong drug if there’s another path you can try and save society some money as well as the time and energy it takes to monitor the patients – as well as the patient’s pain,” he said.
 

How the MSRC test works

The MSRC test detects a signal that’s associated with a high or very high likelihood of inadequate response to TNFi therapies and indicates that the patient is unlikely to achieve low disease activity or remission with TNFi therapies. Response is defined as achieving ACR50 – meaning 50% improvement in American College of Rheumatology response criteria – at 6 months.

Test results are reported on a continuous 1-25 scale, explained Slava Akmaev, PhD, chief technology officer and head of therapeutics at Scipher. “The higher the score, the more likely the patient will have an inadequate response to TNFi therapies and be unable to reach low disease activity; the lower the score, the less likely the patient will have an inadequate response to TNFi therapies,” he said. However, Dr. Akmaev noted that a low score does not ensure a positive response to TNFi therapies.

The MSRC test differs from the multibiomarker disease activity blood test (MBDA; marketed as Vectra by Myriad Genetics) in the number of biomarkers it measures: 19 RNA transcripts vs. 12 serum protein biomarkers in MBDA. The MBDA test is also intended to provide a quantitative, objective measurement of RA disease activity rather than to predict nonresponse to TNFi or other biologics. A number of studies have validated the MBDA test for predicting disease control in RA patients, but not necessarily response to TNFi therapy.

The “high” category threshold of the MSRC test corresponds to an approximate 90% chance of inadequate response to TNFi therapy, or a 10% chance of responding. The “very high” category threshold corresponds to an approximate 95% chance of inadequate response to TNFi therapy, Dr. Akmaev said.

NETWORK-004 used area under the curve (AUC) to measure the accuracy of the MSRC test. An AUC of 1 represents 100% accuracy. Overall, the MSRC had an AUC of 0.64, or 64% accuracy of predicting patients unlikely to respond to TNFi therapy and to achieve ACR50 at 6 months, with an odds ratio of 4.1 (95% confidence interval, 2.0-8.3; P = .0001).

The predictive accuracy went up to 74% with ORs of 3.4-8.8 for additional endpoints at 3 and 6 months (P < .01). Among patients who had already been on TNFi therapy, the predictive accuracy was 83% and associated with ORs of 3.3-26.6 based on ACR, 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), and Clinical Disease Activity Index (CDAI) metrics.

The investigators also performed an in-cohort cross-validation of the MSRC using baseline blood samples of 245 treatment-naive patients from the CERTAIN study, which yielded a 66% predictive accuracy for the ACR50 outcome at 6 months. Using the 19 RNA transcripts from the test, but not the clinical factors, the predictive accuracy was 62.5%. Using ACR70, CDAI, and DAS28 as measures for 6-month response, the cross-validation analysis of all 23 MSRC features yielded predictive accuracy of 64%-67%.

The study found significant differences in model scores between patients who did and did not have the molecular signal of nonresponse, and the proportion of patients who achieved low disease activity or remission at 6 months based on CDAI and DAS28-CRP measures was greater among those who lacked a molecular signature of nonresponse.

“Those who lack this signature can proceed with TNFi therapy and possibly achieve an increased response rate relative to the unstratified population,” wrote lead study author Stanley B. Cohen, MD, and colleagues.

Daniel E. Furst, MD, emeritus professor at the University of California, Los Angeles, described the design of the NETWORK-004 study as “excellent,” but said that it didn’t overcome potential issues with the MSRC test itself. “The results unfortunately are great for group data but not for individuals, with a predictive area under the curve of 60% to 80%, it really is not that useful,” he said. “Let’s say you’re a patient who’s not doing well, and I do a test and it’s positive; that still means that 20% of the time you will respond.”

He also noted that he coauthored a paper that used decreases in DAS28 to predict nonresponse to certolizumab pegol plus methotrexate with 95% probability in the first 12 weeks of treatment. “That’s closer to what we need,” Dr. Furst said.

However, the MSRC test is a promising sign of where testing for predicting RA therapy is headed, he said. “We are steadily working toward genetic signatures that really are predictive on an individual basis,” Dr. Furst said. “It’s coming; it’s just not here yet.”

Dr. Furst had no relevant financial relationships to disclose. Dr. Soloman is a paid investigator and consultant to Scipher Medicine.
 

People beginning treatment with the immunosuppressive drugs tocilizumab (Actemra) or tofacitinib (Xeljanz) are infrequently screened for hepatitis B virus (HBV) infection, according to a new study of patients with rheumatic diseases who are starting one of the two treatments.

“Perhaps not unexpectedly, these screening patterns conform more with recommendations from the American College of Rheumatology, which do not explicitly stipulate universal HBV screening,” wrote lead author Amir M. Mohareb, MD, of Massachusetts General Hospital in Boston. The study was published in The Journal of Rheumatology.

To determine the frequency of HBV screening among this specific population, the researchers conducted a retrospective, cross-sectional study of patients 18 years or older within the Mass General Brigham health system in the Boston area who initiated either of the two drugs before Dec. 31, 2018. Tocilizumab was approved by the Food and Drug Administration on Jan. 11, 2010, and tofacitinib was approved on Nov. 6, 2012.

The final study population included 678 patients on tocilizumab and 391 patients on tofacitinib. The mean age of the patients in each group was 61 years for tocilizumab and 60 years for tofacitinib. A large majority were female (78% of the tocilizumab group, 88% of the tofacitinib group) and 84% of patients in both groups were white. Their primary diagnosis was rheumatoid arthritis (53% of the tocilizumab group, 77% of the tofacitinib group), and most of them – 57% of patients on tocilizumab and 72% of patients on tofacitinib – had a history of being on both conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs).

HBV screening patterns were classified into three categories: complete (all three of the HBV surface antigen [HBsAg], total core antibody [anti-HBcAb], and surface antibody [HBsAb] tests); partial (any one to two tests); and none. Of the 678 patients on tocilizumab, 194 (29%) underwent complete screening, 307 (45%) underwent partial screening, and 177 (26%) had no screening. Of the 391 patients on tofacitinib, 94 (24%) underwent complete screening, 195 (50%) underwent partial screening, and 102 (26%) had none.

Inappropriate testing – defined as either HBV e-antigen (HBeAg), anti-HBcAb IgM, or HBV DNA without a positive HBsAg or total anti-HBcAb – occurred in 22% of patients on tocilizumab and 23% of patients on tofacitinib. After multivariable analysis, the authors found that Whites were less likely to undergo complete screening (odds ratio, 0.74; 95% confidence interval, 0.57-0.95) compared to non-Whites. Previous use of immunosuppressive agents such as conventional synthetic DMARDs (OR, 1.05; 95% CI, 0.72-1.55) and biologic DMARDs with or without prior csDMARDs (OR, 0.73; 95% CI, 0.48-1.12) was not associated with a likelihood of complete appropriate screening.

“These data add to the evidence indicating that clinicians are not completing pretreatment screening for latent infections prior to patients starting high-risk immunosuppressant drugs,” Gabriela Schmajuk, MD, of the University of California, San Francisco, said in an interview. “It can be dangerous, since a fraction of these patients may reactivate latent infections with HBV that can result in liver failure or death.

“On the bright side,” she added, “we have antivirals that can be given as prophylaxis against reactivation of latent HBV if patients do test positive.”

Dr. Schmajuk was previously the senior author of a similar study from the 2019 American College of Rheumatology annual meeting that found only a small percentage of patients who were new users of biologics or new synthetic DMARDs were screened for HBV or hepatitis C virus.

When asked if anything in the study stood out, she acknowledged being “somewhat surprised that patients with prior immunosuppression did not have higher rates of screening. One might expect that since those patients had more opportunities for screening – since they started new medications more times – they would have higher rates, but this did not appear to be the case.”

As a message to rheumatologists who may be starting their patients on any biologic or new synthetic DMARD, she reinforced that “we need universal HBV screening for patients starting these medications. Many clinicians are used to ordering a hepatitis B surface antigen test, but one key message is that we also need to be ordering hepatitis B core antibody tests. Patients with a positive core antibody are still at risk for reactivation.”

The authors noted their study’s limitations, including the data being retrospectively collected and some of the subjects potentially being screened in laboratories outside of the Mass General Brigham health system. In addition, they stated that their findings “may not be generalizable to nonrheumatologic settings or other immunomodulators,” although they added that studies of other patient populations have also uncovered “similarly low HBV screening frequencies.”

Several of the authors reported being supported by institutes within the National Institutes of Health. Beyond that, they declared no potential conflicts of interest.

People beginning treatment with the immunosuppressive drugs tocilizumab (Actemra) or tofacitinib (Xeljanz) are infrequently screened for hepatitis B virus (HBV) infection, according to a new study of patients with rheumatic diseases who are starting one of the two treatments.

“Perhaps not unexpectedly, these screening patterns conform more with recommendations from the American College of Rheumatology, which do not explicitly stipulate universal HBV screening,” wrote lead author Amir M. Mohareb, MD, of Massachusetts General Hospital in Boston. The study was published in The Journal of Rheumatology.

To determine the frequency of HBV screening among this specific population, the researchers conducted a retrospective, cross-sectional study of patients 18 years or older within the Mass General Brigham health system in the Boston area who initiated either of the two drugs before Dec. 31, 2018. Tocilizumab was approved by the Food and Drug Administration on Jan. 11, 2010, and tofacitinib was approved on Nov. 6, 2012.

The final study population included 678 patients on tocilizumab and 391 patients on tofacitinib. The mean age of the patients in each group was 61 years for tocilizumab and 60 years for tofacitinib. A large majority were female (78% of the tocilizumab group, 88% of the tofacitinib group) and 84% of patients in both groups were white. Their primary diagnosis was rheumatoid arthritis (53% of the tocilizumab group, 77% of the tofacitinib group), and most of them – 57% of patients on tocilizumab and 72% of patients on tofacitinib – had a history of being on both conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs).

HBV screening patterns were classified into three categories: complete (all three of the HBV surface antigen [HBsAg], total core antibody [anti-HBcAb], and surface antibody [HBsAb] tests); partial (any one to two tests); and none. Of the 678 patients on tocilizumab, 194 (29%) underwent complete screening, 307 (45%) underwent partial screening, and 177 (26%) had no screening. Of the 391 patients on tofacitinib, 94 (24%) underwent complete screening, 195 (50%) underwent partial screening, and 102 (26%) had none.

Inappropriate testing – defined as either HBV e-antigen (HBeAg), anti-HBcAb IgM, or HBV DNA without a positive HBsAg or total anti-HBcAb – occurred in 22% of patients on tocilizumab and 23% of patients on tofacitinib. After multivariable analysis, the authors found that Whites were less likely to undergo complete screening (odds ratio, 0.74; 95% confidence interval, 0.57-0.95) compared to non-Whites. Previous use of immunosuppressive agents such as conventional synthetic DMARDs (OR, 1.05; 95% CI, 0.72-1.55) and biologic DMARDs with or without prior csDMARDs (OR, 0.73; 95% CI, 0.48-1.12) was not associated with a likelihood of complete appropriate screening.

“These data add to the evidence indicating that clinicians are not completing pretreatment screening for latent infections prior to patients starting high-risk immunosuppressant drugs,” Gabriela Schmajuk, MD, of the University of California, San Francisco, said in an interview. “It can be dangerous, since a fraction of these patients may reactivate latent infections with HBV that can result in liver failure or death.

“On the bright side,” she added, “we have antivirals that can be given as prophylaxis against reactivation of latent HBV if patients do test positive.”

Dr. Schmajuk was previously the senior author of a similar study from the 2019 American College of Rheumatology annual meeting that found only a small percentage of patients who were new users of biologics or new synthetic DMARDs were screened for HBV or hepatitis C virus.

When asked if anything in the study stood out, she acknowledged being “somewhat surprised that patients with prior immunosuppression did not have higher rates of screening. One might expect that since those patients had more opportunities for screening – since they started new medications more times – they would have higher rates, but this did not appear to be the case.”

As a message to rheumatologists who may be starting their patients on any biologic or new synthetic DMARD, she reinforced that “we need universal HBV screening for patients starting these medications. Many clinicians are used to ordering a hepatitis B surface antigen test, but one key message is that we also need to be ordering hepatitis B core antibody tests. Patients with a positive core antibody are still at risk for reactivation.”

The authors noted their study’s limitations, including the data being retrospectively collected and some of the subjects potentially being screened in laboratories outside of the Mass General Brigham health system. In addition, they stated that their findings “may not be generalizable to nonrheumatologic settings or other immunomodulators,” although they added that studies of other patient populations have also uncovered “similarly low HBV screening frequencies.”

Several of the authors reported being supported by institutes within the National Institutes of Health. Beyond that, they declared no potential conflicts of interest.

People beginning treatment with the immunosuppressive drugs tocilizumab (Actemra) or tofacitinib (Xeljanz) are infrequently screened for hepatitis B virus (HBV) infection, according to a new study of patients with rheumatic diseases who are starting one of the two treatments.

“Perhaps not unexpectedly, these screening patterns conform more with recommendations from the American College of Rheumatology, which do not explicitly stipulate universal HBV screening,” wrote lead author Amir M. Mohareb, MD, of Massachusetts General Hospital in Boston. The study was published in The Journal of Rheumatology.

To determine the frequency of HBV screening among this specific population, the researchers conducted a retrospective, cross-sectional study of patients 18 years or older within the Mass General Brigham health system in the Boston area who initiated either of the two drugs before Dec. 31, 2018. Tocilizumab was approved by the Food and Drug Administration on Jan. 11, 2010, and tofacitinib was approved on Nov. 6, 2012.

The final study population included 678 patients on tocilizumab and 391 patients on tofacitinib. The mean age of the patients in each group was 61 years for tocilizumab and 60 years for tofacitinib. A large majority were female (78% of the tocilizumab group, 88% of the tofacitinib group) and 84% of patients in both groups were white. Their primary diagnosis was rheumatoid arthritis (53% of the tocilizumab group, 77% of the tofacitinib group), and most of them – 57% of patients on tocilizumab and 72% of patients on tofacitinib – had a history of being on both conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs).

HBV screening patterns were classified into three categories: complete (all three of the HBV surface antigen [HBsAg], total core antibody [anti-HBcAb], and surface antibody [HBsAb] tests); partial (any one to two tests); and none. Of the 678 patients on tocilizumab, 194 (29%) underwent complete screening, 307 (45%) underwent partial screening, and 177 (26%) had no screening. Of the 391 patients on tofacitinib, 94 (24%) underwent complete screening, 195 (50%) underwent partial screening, and 102 (26%) had none.

Inappropriate testing – defined as either HBV e-antigen (HBeAg), anti-HBcAb IgM, or HBV DNA without a positive HBsAg or total anti-HBcAb – occurred in 22% of patients on tocilizumab and 23% of patients on tofacitinib. After multivariable analysis, the authors found that Whites were less likely to undergo complete screening (odds ratio, 0.74; 95% confidence interval, 0.57-0.95) compared to non-Whites. Previous use of immunosuppressive agents such as conventional synthetic DMARDs (OR, 1.05; 95% CI, 0.72-1.55) and biologic DMARDs with or without prior csDMARDs (OR, 0.73; 95% CI, 0.48-1.12) was not associated with a likelihood of complete appropriate screening.

“These data add to the evidence indicating that clinicians are not completing pretreatment screening for latent infections prior to patients starting high-risk immunosuppressant drugs,” Gabriela Schmajuk, MD, of the University of California, San Francisco, said in an interview. “It can be dangerous, since a fraction of these patients may reactivate latent infections with HBV that can result in liver failure or death.

“On the bright side,” she added, “we have antivirals that can be given as prophylaxis against reactivation of latent HBV if patients do test positive.”

Dr. Schmajuk was previously the senior author of a similar study from the 2019 American College of Rheumatology annual meeting that found only a small percentage of patients who were new users of biologics or new synthetic DMARDs were screened for HBV or hepatitis C virus.

When asked if anything in the study stood out, she acknowledged being “somewhat surprised that patients with prior immunosuppression did not have higher rates of screening. One might expect that since those patients had more opportunities for screening – since they started new medications more times – they would have higher rates, but this did not appear to be the case.”

As a message to rheumatologists who may be starting their patients on any biologic or new synthetic DMARD, she reinforced that “we need universal HBV screening for patients starting these medications. Many clinicians are used to ordering a hepatitis B surface antigen test, but one key message is that we also need to be ordering hepatitis B core antibody tests. Patients with a positive core antibody are still at risk for reactivation.”

The authors noted their study’s limitations, including the data being retrospectively collected and some of the subjects potentially being screened in laboratories outside of the Mass General Brigham health system. In addition, they stated that their findings “may not be generalizable to nonrheumatologic settings or other immunomodulators,” although they added that studies of other patient populations have also uncovered “similarly low HBV screening frequencies.”

Several of the authors reported being supported by institutes within the National Institutes of Health. Beyond that, they declared no potential conflicts of interest.

Key clinical point: The risk for dementia in patients with rheumatoid arthritis (RA) appears to be decreasing over time even when compared with non-RA referents.

Major finding: The 10-year cumulative incidence of ADRD for incident RA in the 1980s, 1990s and 2000s was 12.7%, 7.2% and 6.2%, respectively. Overall risk for ADRD was higher among patients with RA vs non-RA referents (HR, 1.37; 95% CI, 1.04-1.81), but this gap narrowed over time, with ADRD risk being higher in patients diagnosed with RA vs referents in the 1990s (HR, 1.72; 95% CI, 1.09-2.70) but not in the 2000s (HR, 0.86; 95% CI, 0.51-1.45).

Study details: The data come from a retrospective, population-based cohort study involving 897 patients with RA diagnosed between 1980 and 2009 and matched with 885 non-RA referents.

Disclosures: This study was supported by grants from the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Disease and National Institute of Aging. No conflicts of interest were reported.

Source: Kronzer VL et al. Semin Arthritis Rheum. 2021 Jun 15. doi: 10.1016/j.semarthrit.2021.06.003.

Key clinical point: The risk for dementia in patients with rheumatoid arthritis (RA) appears to be decreasing over time even when compared with non-RA referents.

Major finding: The 10-year cumulative incidence of ADRD for incident RA in the 1980s, 1990s and 2000s was 12.7%, 7.2% and 6.2%, respectively. Overall risk for ADRD was higher among patients with RA vs non-RA referents (HR, 1.37; 95% CI, 1.04-1.81), but this gap narrowed over time, with ADRD risk being higher in patients diagnosed with RA vs referents in the 1990s (HR, 1.72; 95% CI, 1.09-2.70) but not in the 2000s (HR, 0.86; 95% CI, 0.51-1.45).

Study details: The data come from a retrospective, population-based cohort study involving 897 patients with RA diagnosed between 1980 and 2009 and matched with 885 non-RA referents.

Disclosures: This study was supported by grants from the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Disease and National Institute of Aging. No conflicts of interest were reported.

Source: Kronzer VL et al. Semin Arthritis Rheum. 2021 Jun 15. doi: 10.1016/j.semarthrit.2021.06.003.

Key clinical point: The risk for dementia in patients with rheumatoid arthritis (RA) appears to be decreasing over time even when compared with non-RA referents.

Major finding: The 10-year cumulative incidence of ADRD for incident RA in the 1980s, 1990s and 2000s was 12.7%, 7.2% and 6.2%, respectively. Overall risk for ADRD was higher among patients with RA vs non-RA referents (HR, 1.37; 95% CI, 1.04-1.81), but this gap narrowed over time, with ADRD risk being higher in patients diagnosed with RA vs referents in the 1990s (HR, 1.72; 95% CI, 1.09-2.70) but not in the 2000s (HR, 0.86; 95% CI, 0.51-1.45).

Study details: The data come from a retrospective, population-based cohort study involving 897 patients with RA diagnosed between 1980 and 2009 and matched with 885 non-RA referents.

Disclosures: This study was supported by grants from the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Disease and National Institute of Aging. No conflicts of interest were reported.

Source: Kronzer VL et al. Semin Arthritis Rheum. 2021 Jun 15. doi: 10.1016/j.semarthrit.2021.06.003.

Key clinical point: Among patients with rheumatoid arthritis (RA), traditional risk factors for cardiovascular disease (CVD) mostly predicted atherosclerotic CVD (ASCVD), except for obesity, which was a risk factor for unprovoked venous thromboembolism (VTE).

Major finding: Obesity was associated with increased VTE risk (adjusted hazard ratio [aHR], 1.47; 95% confidence interval [CI], 1.14-1.89) and reduced ASCVD risk (aHR, 0.56; 95% CI, 0.48-0.66). Other traditional CVD risk factors such as diabetes (aHR, 1.39; 95% CI, 1.20-1.62), hypertension (aHR, 1.21; 95% CI, 1.07-1.39), and chronic kidney disease (aHR, 1.31; 95% CI, 1.10-1.66) predicted higher ASCVD risk.

Study details: The data come from an analysis of 31,366 patients with RA from a US-wide longitudinal observational registry, who did not have any prior CVD at baseline and active cancer throughout follow-up.

Disclosures: No sources of funding were reported. K Michaud reported receiving grant support from the Rheumatology Research Foundation. No competing interests were declared.

Source: Ozen G et al. RMD Open. 2021 Jun 30. doi: 10.1136/rmdopen-2021-001618.

Key clinical point: Among patients with rheumatoid arthritis (RA), traditional risk factors for cardiovascular disease (CVD) mostly predicted atherosclerotic CVD (ASCVD), except for obesity, which was a risk factor for unprovoked venous thromboembolism (VTE).

Major finding: Obesity was associated with increased VTE risk (adjusted hazard ratio [aHR], 1.47; 95% confidence interval [CI], 1.14-1.89) and reduced ASCVD risk (aHR, 0.56; 95% CI, 0.48-0.66). Other traditional CVD risk factors such as diabetes (aHR, 1.39; 95% CI, 1.20-1.62), hypertension (aHR, 1.21; 95% CI, 1.07-1.39), and chronic kidney disease (aHR, 1.31; 95% CI, 1.10-1.66) predicted higher ASCVD risk.

Study details: The data come from an analysis of 31,366 patients with RA from a US-wide longitudinal observational registry, who did not have any prior CVD at baseline and active cancer throughout follow-up.

Disclosures: No sources of funding were reported. K Michaud reported receiving grant support from the Rheumatology Research Foundation. No competing interests were declared.

Source: Ozen G et al. RMD Open. 2021 Jun 30. doi: 10.1136/rmdopen-2021-001618.

Key clinical point: Among patients with rheumatoid arthritis (RA), traditional risk factors for cardiovascular disease (CVD) mostly predicted atherosclerotic CVD (ASCVD), except for obesity, which was a risk factor for unprovoked venous thromboembolism (VTE).

Major finding: Obesity was associated with increased VTE risk (adjusted hazard ratio [aHR], 1.47; 95% confidence interval [CI], 1.14-1.89) and reduced ASCVD risk (aHR, 0.56; 95% CI, 0.48-0.66). Other traditional CVD risk factors such as diabetes (aHR, 1.39; 95% CI, 1.20-1.62), hypertension (aHR, 1.21; 95% CI, 1.07-1.39), and chronic kidney disease (aHR, 1.31; 95% CI, 1.10-1.66) predicted higher ASCVD risk.

Study details: The data come from an analysis of 31,366 patients with RA from a US-wide longitudinal observational registry, who did not have any prior CVD at baseline and active cancer throughout follow-up.

Disclosures: No sources of funding were reported. K Michaud reported receiving grant support from the Rheumatology Research Foundation. No competing interests were declared.

Source: Ozen G et al. RMD Open. 2021 Jun 30. doi: 10.1136/rmdopen-2021-001618.

Key clinical point: Patients with rheumatoid arthritis (RA) receiving interleukin-6 inhibition (IL-6i) therapy with or without T-cell inhibitors had a significantly lower risk for type 2 diabetes mellitus (T2DM) vs those receiving tumor necrosis factor inhibitors (TNFi) or not receiving any biological disease-modifying antirheumatic drugs (bDMARDs).

Major finding: Compared with patients not receiving bDMARDs, those who received IL-6i and IL-6i+T-cell inhibitors had a significant 37% (hazard ratio [HR], 0.63; P = .021) and 34% (HR, 0.66; P = .019) lower risk for T2DM, respectively, whereas no significant difference was observed among patients receiving TNFi (HR, 0.99; P = .26) and T-cell inhibitors (HR, 0.96; P = .37).

Study details: This was a retrospective cohort study of 283,756 patients with RA categorized as bDMARD recipients (TNFi, n=34,873; IL-6i, n=1,884; T-cell inhibitors, n=5,935; and IL-6i+T-cell inhibitor abatacept, n=1,213) and non-bDMARD recipients (n=125,337).

Disclosures: This study was supported by Roche/Genentech. The principal author reported receiving grants, consultancy, and/or speaker fees from various sources. JH Best, S Gale, and K Sarsour reported being employees of Genentech.

Source: Paul SK et al. BMJ Open. 2021 Jun 16. doi: 10.1136/bmjopen-2020-042246.

Key clinical point: Patients with rheumatoid arthritis (RA) receiving interleukin-6 inhibition (IL-6i) therapy with or without T-cell inhibitors had a significantly lower risk for type 2 diabetes mellitus (T2DM) vs those receiving tumor necrosis factor inhibitors (TNFi) or not receiving any biological disease-modifying antirheumatic drugs (bDMARDs).

Major finding: Compared with patients not receiving bDMARDs, those who received IL-6i and IL-6i+T-cell inhibitors had a significant 37% (hazard ratio [HR], 0.63; P = .021) and 34% (HR, 0.66; P = .019) lower risk for T2DM, respectively, whereas no significant difference was observed among patients receiving TNFi (HR, 0.99; P = .26) and T-cell inhibitors (HR, 0.96; P = .37).

Study details: This was a retrospective cohort study of 283,756 patients with RA categorized as bDMARD recipients (TNFi, n=34,873; IL-6i, n=1,884; T-cell inhibitors, n=5,935; and IL-6i+T-cell inhibitor abatacept, n=1,213) and non-bDMARD recipients (n=125,337).

Disclosures: This study was supported by Roche/Genentech. The principal author reported receiving grants, consultancy, and/or speaker fees from various sources. JH Best, S Gale, and K Sarsour reported being employees of Genentech.

Source: Paul SK et al. BMJ Open. 2021 Jun 16. doi: 10.1136/bmjopen-2020-042246.

Key clinical point: Patients with rheumatoid arthritis (RA) receiving interleukin-6 inhibition (IL-6i) therapy with or without T-cell inhibitors had a significantly lower risk for type 2 diabetes mellitus (T2DM) vs those receiving tumor necrosis factor inhibitors (TNFi) or not receiving any biological disease-modifying antirheumatic drugs (bDMARDs).

Major finding: Compared with patients not receiving bDMARDs, those who received IL-6i and IL-6i+T-cell inhibitors had a significant 37% (hazard ratio [HR], 0.63; P = .021) and 34% (HR, 0.66; P = .019) lower risk for T2DM, respectively, whereas no significant difference was observed among patients receiving TNFi (HR, 0.99; P = .26) and T-cell inhibitors (HR, 0.96; P = .37).

Study details: This was a retrospective cohort study of 283,756 patients with RA categorized as bDMARD recipients (TNFi, n=34,873; IL-6i, n=1,884; T-cell inhibitors, n=5,935; and IL-6i+T-cell inhibitor abatacept, n=1,213) and non-bDMARD recipients (n=125,337).

Disclosures: This study was supported by Roche/Genentech. The principal author reported receiving grants, consultancy, and/or speaker fees from various sources. JH Best, S Gale, and K Sarsour reported being employees of Genentech.

Source: Paul SK et al. BMJ Open. 2021 Jun 16. doi: 10.1136/bmjopen-2020-042246.

Key clinical point: Despite limited radiological damage, rapid radiological progression (RRP) still occurred in about 1 of 5 patients in a real-world cohort of patients with rheumatoid arthritis (RA) treated to the target of remission. RRP was most strongly predicted by baseline erosive disease.

Major finding: Most radiological damage occurred in the first year of treatment vs subsequent 5 years of follow-up (median Sharp/van der Heijde score, 2.0 vs 3.0). Despite achieving low disease activity, almost 18.8% of the patients developed RRP within 6 months, and the number of patients with erosive disease increased from 16% at baseline to 58% at 6 years. The erosive disease was the strongest predictor of RRP (odds ratio, 8.8; P less than .001).

Study details: Findings are from the observational DREAM remission induction cohort involving 219 patients diagnosed with RA who had at least 1 radiograph of hands and feet at baseline and at least 1 additional pair of radiographs during 6 years of follow-up and were treated to the target of remission.

Disclosures: No external funding and/or potential conflicts of interest were reported.

Source: Versteeg GA et al. Scand J Rheumatol. 2021 Jun 21. doi: 10.1080/03009742.2021.1917161.

Key clinical point: Despite limited radiological damage, rapid radiological progression (RRP) still occurred in about 1 of 5 patients in a real-world cohort of patients with rheumatoid arthritis (RA) treated to the target of remission. RRP was most strongly predicted by baseline erosive disease.

Major finding: Most radiological damage occurred in the first year of treatment vs subsequent 5 years of follow-up (median Sharp/van der Heijde score, 2.0 vs 3.0). Despite achieving low disease activity, almost 18.8% of the patients developed RRP within 6 months, and the number of patients with erosive disease increased from 16% at baseline to 58% at 6 years. The erosive disease was the strongest predictor of RRP (odds ratio, 8.8; P less than .001).

Study details: Findings are from the observational DREAM remission induction cohort involving 219 patients diagnosed with RA who had at least 1 radiograph of hands and feet at baseline and at least 1 additional pair of radiographs during 6 years of follow-up and were treated to the target of remission.

Disclosures: No external funding and/or potential conflicts of interest were reported.

Source: Versteeg GA et al. Scand J Rheumatol. 2021 Jun 21. doi: 10.1080/03009742.2021.1917161.

Key clinical point: Despite limited radiological damage, rapid radiological progression (RRP) still occurred in about 1 of 5 patients in a real-world cohort of patients with rheumatoid arthritis (RA) treated to the target of remission. RRP was most strongly predicted by baseline erosive disease.

Major finding: Most radiological damage occurred in the first year of treatment vs subsequent 5 years of follow-up (median Sharp/van der Heijde score, 2.0 vs 3.0). Despite achieving low disease activity, almost 18.8% of the patients developed RRP within 6 months, and the number of patients with erosive disease increased from 16% at baseline to 58% at 6 years. The erosive disease was the strongest predictor of RRP (odds ratio, 8.8; P less than .001).

Study details: Findings are from the observational DREAM remission induction cohort involving 219 patients diagnosed with RA who had at least 1 radiograph of hands and feet at baseline and at least 1 additional pair of radiographs during 6 years of follow-up and were treated to the target of remission.

Disclosures: No external funding and/or potential conflicts of interest were reported.

Source: Versteeg GA et al. Scand J Rheumatol. 2021 Jun 21. doi: 10.1080/03009742.2021.1917161.

Key clinical point: Sarcopenia and low muscle mass are common comorbidities among middle-aged and elderly patients with rheumatoid arthritis (RA). Corticosteroid therapy was positively and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were inversely associated with sarcopenia.

Major finding: Overall, the prevalence of low muscle mass and sarcopenia was 30.2% (95% confidence interval [CI], 24.2%-36.2%). The use of csDMARDs was inversely (odds ratio [OR], 0.70; P = .019) and corticosteroid was positively (OR, 1.46; 95% CI, 0.94-2.29) associated with sarcopenia. No association was observed between biological/targeted DMARDs and sarcopenia (OR, 0.83; P = .420).

Study details: Findings are from a meta-analysis of 16 observational studies involving 2,240 middle-aged and older adults with RA.

Disclosures: No specific funding was received for this study. All the authors declared no conflicts of interest.

Source: Dao T et al. Calcif Tissue Int. 2021 Jun 16. doi: 10.1007/s00223-021-00873-w.

Key clinical point: Sarcopenia and low muscle mass are common comorbidities among middle-aged and elderly patients with rheumatoid arthritis (RA). Corticosteroid therapy was positively and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were inversely associated with sarcopenia.

Major finding: Overall, the prevalence of low muscle mass and sarcopenia was 30.2% (95% confidence interval [CI], 24.2%-36.2%). The use of csDMARDs was inversely (odds ratio [OR], 0.70; P = .019) and corticosteroid was positively (OR, 1.46; 95% CI, 0.94-2.29) associated with sarcopenia. No association was observed between biological/targeted DMARDs and sarcopenia (OR, 0.83; P = .420).

Study details: Findings are from a meta-analysis of 16 observational studies involving 2,240 middle-aged and older adults with RA.

Disclosures: No specific funding was received for this study. All the authors declared no conflicts of interest.

Source: Dao T et al. Calcif Tissue Int. 2021 Jun 16. doi: 10.1007/s00223-021-00873-w.

Key clinical point: Sarcopenia and low muscle mass are common comorbidities among middle-aged and elderly patients with rheumatoid arthritis (RA). Corticosteroid therapy was positively and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were inversely associated with sarcopenia.

Major finding: Overall, the prevalence of low muscle mass and sarcopenia was 30.2% (95% confidence interval [CI], 24.2%-36.2%). The use of csDMARDs was inversely (odds ratio [OR], 0.70; P = .019) and corticosteroid was positively (OR, 1.46; 95% CI, 0.94-2.29) associated with sarcopenia. No association was observed between biological/targeted DMARDs and sarcopenia (OR, 0.83; P = .420).

Study details: Findings are from a meta-analysis of 16 observational studies involving 2,240 middle-aged and older adults with RA.

Disclosures: No specific funding was received for this study. All the authors declared no conflicts of interest.

Source: Dao T et al. Calcif Tissue Int. 2021 Jun 16. doi: 10.1007/s00223-021-00873-w.

Key clinical point: Almost one-third of patients with new-onset rheumatoid arthritis (RA) had long-lasting unacceptable pain. Patients with a less inflammatory disease at baseline, in the form of lower swollen joint count (SJC), were at an increased risk for unacceptable pain at 5 years.

Major finding: Almost 49.1% of patients had unacceptable pain at inclusion, which decreased to 30.1% during the first year and remained unchanged thereafter. At 5 years, lower SJC (adjusted odds ratio [aOR] per standard deviation, 0.61; P = .01) was a significant predictor of unacceptable pain.

Study details: The data come from an inception cohort of 232 patients with early RA with symptom duration of at least 12 months.

Disclosures: This work was supported by the Swedish Research Council, the Swedish Rheumatism Association, and Lund University. Some of the authors declared receiving grants, personal fees, and lecture/consulting fees from and/or being an employee of or working as a medical advisor for various sources.

Source: Eberhard A et al. Arthritis Res Ther. 2021 Jun 14. doi: 10.1186/s13075-021-02550-7.

Key clinical point: Almost one-third of patients with new-onset rheumatoid arthritis (RA) had long-lasting unacceptable pain. Patients with a less inflammatory disease at baseline, in the form of lower swollen joint count (SJC), were at an increased risk for unacceptable pain at 5 years.

Major finding: Almost 49.1% of patients had unacceptable pain at inclusion, which decreased to 30.1% during the first year and remained unchanged thereafter. At 5 years, lower SJC (adjusted odds ratio [aOR] per standard deviation, 0.61; P = .01) was a significant predictor of unacceptable pain.

Study details: The data come from an inception cohort of 232 patients with early RA with symptom duration of at least 12 months.

Disclosures: This work was supported by the Swedish Research Council, the Swedish Rheumatism Association, and Lund University. Some of the authors declared receiving grants, personal fees, and lecture/consulting fees from and/or being an employee of or working as a medical advisor for various sources.

Source: Eberhard A et al. Arthritis Res Ther. 2021 Jun 14. doi: 10.1186/s13075-021-02550-7.

Key clinical point: Almost one-third of patients with new-onset rheumatoid arthritis (RA) had long-lasting unacceptable pain. Patients with a less inflammatory disease at baseline, in the form of lower swollen joint count (SJC), were at an increased risk for unacceptable pain at 5 years.

Major finding: Almost 49.1% of patients had unacceptable pain at inclusion, which decreased to 30.1% during the first year and remained unchanged thereafter. At 5 years, lower SJC (adjusted odds ratio [aOR] per standard deviation, 0.61; P = .01) was a significant predictor of unacceptable pain.

Study details: The data come from an inception cohort of 232 patients with early RA with symptom duration of at least 12 months.

Disclosures: This work was supported by the Swedish Research Council, the Swedish Rheumatism Association, and Lund University. Some of the authors declared receiving grants, personal fees, and lecture/consulting fees from and/or being an employee of or working as a medical advisor for various sources.

Source: Eberhard A et al. Arthritis Res Ther. 2021 Jun 14. doi: 10.1186/s13075-021-02550-7.

Key clinical point: The long-term safety profile of sarilumab was consistent with prior clinical studies and postmarketing reports in patients with rheumatoid arthritis (RA) refractory to tumor necrosis factor inhibitors (TNFi).

Major finding: Incidence rates of adverse events (AEs) and serious AEs were 160.4 and 10.2 per 100 patient-years (PY), respectively, with 132 discontinuations (8.1/100 PY). The rate of serious infections was 3.9 per 100 PY. Grade 3/4 neutropenia was observed in 14% of patients and normalized on treatment in 65% of patients. Clinical efficacy was sustained throughout the 5-year follow-up.

Study details: Findings are from the open-label extension (OLE), EXTEND study, which included 454 patients with TNFi-refractory RA who completed the phase 3 TARGET study. In the OLE, patients received sarilumab 200 mg twice per week plus conventional synthetic disease-modifying antirheumatic drugs.

Disclosures: This work was supported by Sanofi (Cambridge, MA, USA) and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY, USA). Some of the authors reported receiving research grants and/or consulting fees from various sources. Some authors declared being an employee of and/or holding stocks/stock options at Sanofi or Regeneron Pharmaceuticals, Inc.

Source: Fleischmann R et al. Rheumatology (Oxford). 2021 Jun 24. doi: 10.1093/rheumatology/keab355.

Key clinical point: The long-term safety profile of sarilumab was consistent with prior clinical studies and postmarketing reports in patients with rheumatoid arthritis (RA) refractory to tumor necrosis factor inhibitors (TNFi).

Major finding: Incidence rates of adverse events (AEs) and serious AEs were 160.4 and 10.2 per 100 patient-years (PY), respectively, with 132 discontinuations (8.1/100 PY). The rate of serious infections was 3.9 per 100 PY. Grade 3/4 neutropenia was observed in 14% of patients and normalized on treatment in 65% of patients. Clinical efficacy was sustained throughout the 5-year follow-up.

Study details: Findings are from the open-label extension (OLE), EXTEND study, which included 454 patients with TNFi-refractory RA who completed the phase 3 TARGET study. In the OLE, patients received sarilumab 200 mg twice per week plus conventional synthetic disease-modifying antirheumatic drugs.

Disclosures: This work was supported by Sanofi (Cambridge, MA, USA) and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY, USA). Some of the authors reported receiving research grants and/or consulting fees from various sources. Some authors declared being an employee of and/or holding stocks/stock options at Sanofi or Regeneron Pharmaceuticals, Inc.

Source: Fleischmann R et al. Rheumatology (Oxford). 2021 Jun 24. doi: 10.1093/rheumatology/keab355.

Key clinical point: The long-term safety profile of sarilumab was consistent with prior clinical studies and postmarketing reports in patients with rheumatoid arthritis (RA) refractory to tumor necrosis factor inhibitors (TNFi).

Major finding: Incidence rates of adverse events (AEs) and serious AEs were 160.4 and 10.2 per 100 patient-years (PY), respectively, with 132 discontinuations (8.1/100 PY). The rate of serious infections was 3.9 per 100 PY. Grade 3/4 neutropenia was observed in 14% of patients and normalized on treatment in 65% of patients. Clinical efficacy was sustained throughout the 5-year follow-up.

Study details: Findings are from the open-label extension (OLE), EXTEND study, which included 454 patients with TNFi-refractory RA who completed the phase 3 TARGET study. In the OLE, patients received sarilumab 200 mg twice per week plus conventional synthetic disease-modifying antirheumatic drugs.

Disclosures: This work was supported by Sanofi (Cambridge, MA, USA) and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY, USA). Some of the authors reported receiving research grants and/or consulting fees from various sources. Some authors declared being an employee of and/or holding stocks/stock options at Sanofi or Regeneron Pharmaceuticals, Inc.

Source: Fleischmann R et al. Rheumatology (Oxford). 2021 Jun 24. doi: 10.1093/rheumatology/keab355.

Key clinical point: Systemic glucocorticoids (GCs) were effective at reducing pain in patients with active rheumatoid arthritis (RA), with the effect being greatest within 3 months of initiation, whereas it appeared to be less effective beyond 6 months.

Major finding: Treatment with systemic GCs significantly decreased spontaneous pain (standardized mean differences [MD], −0.67; 95% confidence interval [CI], −0.84 to −0.50), with the effect being greatest at 3 months or lesser (MD, −14.55 mm; 95% CI, −20.40 to −8.69) and appeared to be less effective at more than 3 to 6 months (MD, −7.82 mm; 95% CI, −12.27 to -3.38) and beyond 6 months (MD, −6.52 mm; 95% CI, −13.28 to 0.24).

Study details: Findings are from a systematic review and meta-analysis of 33 randomized controlled trials including 2,658 patients with RA.

Disclosures: The study received no specific funding. D McWilliams, DA Walsh, and NG Shanker reported receiving grant support and consultancy fees from various sources like Pfizer Ltd., Eli Lilly, UCB, AbbVie, GSK, and Cambridge Nutraceuticals.

Source: McWilliams DF et al. Rheumatology (Oxford). 2021 Jul 2. doi: 10.1093/rheumatology/keab503.

Key clinical point: Systemic glucocorticoids (GCs) were effective at reducing pain in patients with active rheumatoid arthritis (RA), with the effect being greatest within 3 months of initiation, whereas it appeared to be less effective beyond 6 months.

Major finding: Treatment with systemic GCs significantly decreased spontaneous pain (standardized mean differences [MD], −0.67; 95% confidence interval [CI], −0.84 to −0.50), with the effect being greatest at 3 months or lesser (MD, −14.55 mm; 95% CI, −20.40 to −8.69) and appeared to be less effective at more than 3 to 6 months (MD, −7.82 mm; 95% CI, −12.27 to -3.38) and beyond 6 months (MD, −6.52 mm; 95% CI, −13.28 to 0.24).

Study details: Findings are from a systematic review and meta-analysis of 33 randomized controlled trials including 2,658 patients with RA.

Disclosures: The study received no specific funding. D McWilliams, DA Walsh, and NG Shanker reported receiving grant support and consultancy fees from various sources like Pfizer Ltd., Eli Lilly, UCB, AbbVie, GSK, and Cambridge Nutraceuticals.

Source: McWilliams DF et al. Rheumatology (Oxford). 2021 Jul 2. doi: 10.1093/rheumatology/keab503.

Key clinical point: Systemic glucocorticoids (GCs) were effective at reducing pain in patients with active rheumatoid arthritis (RA), with the effect being greatest within 3 months of initiation, whereas it appeared to be less effective beyond 6 months.

Major finding: Treatment with systemic GCs significantly decreased spontaneous pain (standardized mean differences [MD], −0.67; 95% confidence interval [CI], −0.84 to −0.50), with the effect being greatest at 3 months or lesser (MD, −14.55 mm; 95% CI, −20.40 to −8.69) and appeared to be less effective at more than 3 to 6 months (MD, −7.82 mm; 95% CI, −12.27 to -3.38) and beyond 6 months (MD, −6.52 mm; 95% CI, −13.28 to 0.24).

Study details: Findings are from a systematic review and meta-analysis of 33 randomized controlled trials including 2,658 patients with RA.

Disclosures: The study received no specific funding. D McWilliams, DA Walsh, and NG Shanker reported receiving grant support and consultancy fees from various sources like Pfizer Ltd., Eli Lilly, UCB, AbbVie, GSK, and Cambridge Nutraceuticals.

Source: McWilliams DF et al. Rheumatology (Oxford). 2021 Jul 2. doi: 10.1093/rheumatology/keab503.