Rheumatoid Arthritis

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Patients with undifferentiated arthritis (UA) that is defined according to contemporary criteria don’t appear to have the same excess mortality that is associated with rheumatoid arthritis, despite links between the two conditions.

UA has long been considered an earlier phase of RA, so similar management strategies are often used based on the assumption that outcomes and elevated mortality risk were similar between the two, but new findings reported in a research letter published in Annals of the Rheumatic Diseases challenge that assumption.

The change in the definition of UA that accompanied the introduction of new RA criteria in 2010 meant that some of the patients who previously met the criteria for UA now were classified as having RA, and “the remaining contemporary UA population (not fulfilling the 1987/2010 RA criteria) is largely autoantibody negative, presents with monoarthritis or oligoarthritis, and progresses less frequently to RA,” PhD candidate Marloes Verstappen of Leiden (Netherlands) University Medical Center, and coauthors wrote.

As the first large study on excess mortality in patients meeting contemporary criteria for UA, the authors said it suggests that the change in criteria for UA has served to increase the differences in mortality between it and RA.

“Further research and discussions are needed as to whether the management of contemporary UA should be similar to or different from that of RA,” they wrote.

The researchers conducted a longitudinal cohort study of 860 patients who met the conventional criteria for UA – they did not meet the 1987 RA criteria or other diagnosis – at baseline and 561 who met contemporary criteria for UA based on the fact that they did not meet the 1987 or 2010 RA criteria. There were also 762 patients who were diagnosed with RA according to the 1987 criteria, and 828 diagnosed according to the 2010 criteria. All of these patients were diagnosed between 1993 and 2008 and their median follow-up times ranged from 16.0 to 17.3 years, with a minimum of 10 years of follow-up.

The study found that, while there was a trend toward excess mortality in the conventional UA group (standardized mortality ratio, 1.11; 95% confidence interval, 0.96-1.27), there was no significant excess mortality in the contemporary UA patients (SMR, 1.05; 95% CI, 0.87-1.26).

In comparison, patients in both the 1987 RA criteria group and the 2010 criteria group showed significantly higher mortality. Among patients with anti–citrullinated protein antibody–positive disease, even early treatment with disease-modifying antirheumatic drugs and treat-to-target strategies didn’t reduce the excess mortality.

The study did find some suggestion of excess mortality among patients with contemporary UA and who were anti–citrullinated protein antibody positive, but the number of patients was small.

“Only a few percent of patients presenting with contemporary UA are autoantibody positive; these patients may be considered at increased risk to progress to RA,” the authors wrote.

The data also suggested that disease-modifying antirheumatic drugs didn’t alter excess mortality among patients with contemporary UA.

The study was supported by the Dutch Arthritis Foundation and the European Research Council. No conflicts of interest were declared.

Patients with undifferentiated arthritis (UA) that is defined according to contemporary criteria don’t appear to have the same excess mortality that is associated with rheumatoid arthritis, despite links between the two conditions.

UA has long been considered an earlier phase of RA, so similar management strategies are often used based on the assumption that outcomes and elevated mortality risk were similar between the two, but new findings reported in a research letter published in Annals of the Rheumatic Diseases challenge that assumption.

The change in the definition of UA that accompanied the introduction of new RA criteria in 2010 meant that some of the patients who previously met the criteria for UA now were classified as having RA, and “the remaining contemporary UA population (not fulfilling the 1987/2010 RA criteria) is largely autoantibody negative, presents with monoarthritis or oligoarthritis, and progresses less frequently to RA,” PhD candidate Marloes Verstappen of Leiden (Netherlands) University Medical Center, and coauthors wrote.

As the first large study on excess mortality in patients meeting contemporary criteria for UA, the authors said it suggests that the change in criteria for UA has served to increase the differences in mortality between it and RA.

“Further research and discussions are needed as to whether the management of contemporary UA should be similar to or different from that of RA,” they wrote.

The researchers conducted a longitudinal cohort study of 860 patients who met the conventional criteria for UA – they did not meet the 1987 RA criteria or other diagnosis – at baseline and 561 who met contemporary criteria for UA based on the fact that they did not meet the 1987 or 2010 RA criteria. There were also 762 patients who were diagnosed with RA according to the 1987 criteria, and 828 diagnosed according to the 2010 criteria. All of these patients were diagnosed between 1993 and 2008 and their median follow-up times ranged from 16.0 to 17.3 years, with a minimum of 10 years of follow-up.

The study found that, while there was a trend toward excess mortality in the conventional UA group (standardized mortality ratio, 1.11; 95% confidence interval, 0.96-1.27), there was no significant excess mortality in the contemporary UA patients (SMR, 1.05; 95% CI, 0.87-1.26).

In comparison, patients in both the 1987 RA criteria group and the 2010 criteria group showed significantly higher mortality. Among patients with anti–citrullinated protein antibody–positive disease, even early treatment with disease-modifying antirheumatic drugs and treat-to-target strategies didn’t reduce the excess mortality.

The study did find some suggestion of excess mortality among patients with contemporary UA and who were anti–citrullinated protein antibody positive, but the number of patients was small.

“Only a few percent of patients presenting with contemporary UA are autoantibody positive; these patients may be considered at increased risk to progress to RA,” the authors wrote.

The data also suggested that disease-modifying antirheumatic drugs didn’t alter excess mortality among patients with contemporary UA.

The study was supported by the Dutch Arthritis Foundation and the European Research Council. No conflicts of interest were declared.

Patients with undifferentiated arthritis (UA) that is defined according to contemporary criteria don’t appear to have the same excess mortality that is associated with rheumatoid arthritis, despite links between the two conditions.

UA has long been considered an earlier phase of RA, so similar management strategies are often used based on the assumption that outcomes and elevated mortality risk were similar between the two, but new findings reported in a research letter published in Annals of the Rheumatic Diseases challenge that assumption.

The change in the definition of UA that accompanied the introduction of new RA criteria in 2010 meant that some of the patients who previously met the criteria for UA now were classified as having RA, and “the remaining contemporary UA population (not fulfilling the 1987/2010 RA criteria) is largely autoantibody negative, presents with monoarthritis or oligoarthritis, and progresses less frequently to RA,” PhD candidate Marloes Verstappen of Leiden (Netherlands) University Medical Center, and coauthors wrote.

As the first large study on excess mortality in patients meeting contemporary criteria for UA, the authors said it suggests that the change in criteria for UA has served to increase the differences in mortality between it and RA.

“Further research and discussions are needed as to whether the management of contemporary UA should be similar to or different from that of RA,” they wrote.

The researchers conducted a longitudinal cohort study of 860 patients who met the conventional criteria for UA – they did not meet the 1987 RA criteria or other diagnosis – at baseline and 561 who met contemporary criteria for UA based on the fact that they did not meet the 1987 or 2010 RA criteria. There were also 762 patients who were diagnosed with RA according to the 1987 criteria, and 828 diagnosed according to the 2010 criteria. All of these patients were diagnosed between 1993 and 2008 and their median follow-up times ranged from 16.0 to 17.3 years, with a minimum of 10 years of follow-up.

The study found that, while there was a trend toward excess mortality in the conventional UA group (standardized mortality ratio, 1.11; 95% confidence interval, 0.96-1.27), there was no significant excess mortality in the contemporary UA patients (SMR, 1.05; 95% CI, 0.87-1.26).

In comparison, patients in both the 1987 RA criteria group and the 2010 criteria group showed significantly higher mortality. Among patients with anti–citrullinated protein antibody–positive disease, even early treatment with disease-modifying antirheumatic drugs and treat-to-target strategies didn’t reduce the excess mortality.

The study did find some suggestion of excess mortality among patients with contemporary UA and who were anti–citrullinated protein antibody positive, but the number of patients was small.

“Only a few percent of patients presenting with contemporary UA are autoantibody positive; these patients may be considered at increased risk to progress to RA,” the authors wrote.

The data also suggested that disease-modifying antirheumatic drugs didn’t alter excess mortality among patients with contemporary UA.

The study was supported by the Dutch Arthritis Foundation and the European Research Council. No conflicts of interest were declared.

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

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

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

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

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

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

The recent ORAL Surveillance trial has raised concerns about the safety of tofacitinib (and potentially other JAK inhibitors) in the treatment of rheumatoid arthritis.¹ JAK inhibitors are known to increase cholesterol levels; however, this was not previously known to increase cardiovascular risk. The ORAL Surveillance trial was an open-label randomized non-inferiority trial comparing 5mg or 10 mg tofacitinib twice daily with tumor necrosis factor (TNF) inhibitor use. Both adverse cardiac events and cancer were increased in the tofacitinib groups (with hazard ratios of 1.33 and 1.48, respectively). The study did not include a control group and so the impact of RA itself on cardiac events and cancer is not known. However, the apparent risk was greatest in patients over the age of 65, suggesting caution should be used in treating older patients with RA with JAK inhibitors. Interestingly, the STAR-RA study, an observational cohort study, looked at claims data from several sources to try to replicate trial results as well as provide real-world evidence on the topic of cardiovascular risk associated with tofacitinib use.² The authors were able to replicate the inclusion/exclusion criteria from the ORAL Surveillance trial and found that the results were similar. However, on “relaxing” inclusion and exclusion criteria, ie, the “real-world evidence” cohort, there was no difference in incidence of cardiovascular outcomes between tofacitinib and TNF-inhibitor groups. Specifically, patients in the real-world cohort who had no cardiovascular risk factors or prior events were not found to have an increased cardiovascular risk with tofacitinib use, a reassuring finding supporting careful attention to cardiovascular risk in patients with RA when evaluating treatment options.

One consideration in the use of rituximab for treatment of RA is the possibility of changing or lowering subsequent or maintenance doses. Past studies have suggested that halving the dose of rituximab to a single 1000 mg infusion was tolerated by RA patients. The REDO trial, published in 2019, looked at even lower doses: 500 mg and 200 mg. The study did not establish non-inferiority of lower doses at 6 months in a per-protocol analysis, only in intention-to-treat. An extension study of REDO presented at the ACR Convergence in 2021 looked at a subset of those patients for up to 4 years and did find non-inferiority in terms of disease activity. Wientjes et al³ present further analysis of the REDO trial with 140 RA patients at 6 months, looking at the association of rituximab dosage with B cell counts as well as the predictive value of different patient characteristics in terms of response to lower dosages. Interestingly, serum drug levels and B cell counts at 3 and 6 months did not predict response to rituximab, nor did patient characteristics, such as age, smoking, disease, duration, or seropositivity for RF and CCP. Though the authors suggest that this implies even lower doses may be effective, it is not clear, and a similar analysis of the extension trial would be of interest. 

Use of methotrexate as a first-line DMARD for RA is cost-effective but often limited by patient fears or intolerance due to adverse events (AE). This observational cohort study by Sherbini et al⁴ evaluates not only the prevalence of AE, but also baseline factors that may predict the development of AE. Over 1,000 patients with early RA initiating methotrexate were included in analysis. More than 75% reported at least one AE in 12 months, with gastrointestinal AE, such as nausea, being most prevalent (42%); 18% developed elevated liver enzyme tests (defined as a single reading above the upper limit of normal). Few strong predictors of AE were identified, though women were overall more likely than men to report AE. Reassuringly, combination conventional synthetic DMARD therapy did not generally lead to more reported AE. Given the few predictive findings from this study, analysis of a comparator group or comparison of AE at different starting and maintenance doses of methotrexate would be of interest.

References

1.  Ytterberg SR et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-326 (Jan 27).
2. Khosrow-Khavar F et al. Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study. Ann Rheum Dis. 2022 (Jan 13).
3. Wientjes MHM et al. Drug levels, anti-drug antibodies and B-cell counts were not predictive of response in rheumatoid arthritis patients on (ultra-)low-dose rituximab. Rheumatology (Oxford). 2022 (Jan 12).
4. Sherbini AA et al. Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study. Rheumatology (Oxford). 2022 (Jan 25).

The recent ORAL Surveillance trial has raised concerns about the safety of tofacitinib (and potentially other JAK inhibitors) in the treatment of rheumatoid arthritis.¹ JAK inhibitors are known to increase cholesterol levels; however, this was not previously known to increase cardiovascular risk. The ORAL Surveillance trial was an open-label randomized non-inferiority trial comparing 5mg or 10 mg tofacitinib twice daily with tumor necrosis factor (TNF) inhibitor use. Both adverse cardiac events and cancer were increased in the tofacitinib groups (with hazard ratios of 1.33 and 1.48, respectively). The study did not include a control group and so the impact of RA itself on cardiac events and cancer is not known. However, the apparent risk was greatest in patients over the age of 65, suggesting caution should be used in treating older patients with RA with JAK inhibitors. Interestingly, the STAR-RA study, an observational cohort study, looked at claims data from several sources to try to replicate trial results as well as provide real-world evidence on the topic of cardiovascular risk associated with tofacitinib use.² The authors were able to replicate the inclusion/exclusion criteria from the ORAL Surveillance trial and found that the results were similar. However, on “relaxing” inclusion and exclusion criteria, ie, the “real-world evidence” cohort, there was no difference in incidence of cardiovascular outcomes between tofacitinib and TNF-inhibitor groups. Specifically, patients in the real-world cohort who had no cardiovascular risk factors or prior events were not found to have an increased cardiovascular risk with tofacitinib use, a reassuring finding supporting careful attention to cardiovascular risk in patients with RA when evaluating treatment options.

One consideration in the use of rituximab for treatment of RA is the possibility of changing or lowering subsequent or maintenance doses. Past studies have suggested that halving the dose of rituximab to a single 1000 mg infusion was tolerated by RA patients. The REDO trial, published in 2019, looked at even lower doses: 500 mg and 200 mg. The study did not establish non-inferiority of lower doses at 6 months in a per-protocol analysis, only in intention-to-treat. An extension study of REDO presented at the ACR Convergence in 2021 looked at a subset of those patients for up to 4 years and did find non-inferiority in terms of disease activity. Wientjes et al³ present further analysis of the REDO trial with 140 RA patients at 6 months, looking at the association of rituximab dosage with B cell counts as well as the predictive value of different patient characteristics in terms of response to lower dosages. Interestingly, serum drug levels and B cell counts at 3 and 6 months did not predict response to rituximab, nor did patient characteristics, such as age, smoking, disease, duration, or seropositivity for RF and CCP. Though the authors suggest that this implies even lower doses may be effective, it is not clear, and a similar analysis of the extension trial would be of interest. 

Use of methotrexate as a first-line DMARD for RA is cost-effective but often limited by patient fears or intolerance due to adverse events (AE). This observational cohort study by Sherbini et al⁴ evaluates not only the prevalence of AE, but also baseline factors that may predict the development of AE. Over 1,000 patients with early RA initiating methotrexate were included in analysis. More than 75% reported at least one AE in 12 months, with gastrointestinal AE, such as nausea, being most prevalent (42%); 18% developed elevated liver enzyme tests (defined as a single reading above the upper limit of normal). Few strong predictors of AE were identified, though women were overall more likely than men to report AE. Reassuringly, combination conventional synthetic DMARD therapy did not generally lead to more reported AE. Given the few predictive findings from this study, analysis of a comparator group or comparison of AE at different starting and maintenance doses of methotrexate would be of interest.

References

1.  Ytterberg SR et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-326 (Jan 27).
2. Khosrow-Khavar F et al. Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study. Ann Rheum Dis. 2022 (Jan 13).
3. Wientjes MHM et al. Drug levels, anti-drug antibodies and B-cell counts were not predictive of response in rheumatoid arthritis patients on (ultra-)low-dose rituximab. Rheumatology (Oxford). 2022 (Jan 12).
4. Sherbini AA et al. Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study. Rheumatology (Oxford). 2022 (Jan 25).

The recent ORAL Surveillance trial has raised concerns about the safety of tofacitinib (and potentially other JAK inhibitors) in the treatment of rheumatoid arthritis.¹ JAK inhibitors are known to increase cholesterol levels; however, this was not previously known to increase cardiovascular risk. The ORAL Surveillance trial was an open-label randomized non-inferiority trial comparing 5mg or 10 mg tofacitinib twice daily with tumor necrosis factor (TNF) inhibitor use. Both adverse cardiac events and cancer were increased in the tofacitinib groups (with hazard ratios of 1.33 and 1.48, respectively). The study did not include a control group and so the impact of RA itself on cardiac events and cancer is not known. However, the apparent risk was greatest in patients over the age of 65, suggesting caution should be used in treating older patients with RA with JAK inhibitors. Interestingly, the STAR-RA study, an observational cohort study, looked at claims data from several sources to try to replicate trial results as well as provide real-world evidence on the topic of cardiovascular risk associated with tofacitinib use.² The authors were able to replicate the inclusion/exclusion criteria from the ORAL Surveillance trial and found that the results were similar. However, on “relaxing” inclusion and exclusion criteria, ie, the “real-world evidence” cohort, there was no difference in incidence of cardiovascular outcomes between tofacitinib and TNF-inhibitor groups. Specifically, patients in the real-world cohort who had no cardiovascular risk factors or prior events were not found to have an increased cardiovascular risk with tofacitinib use, a reassuring finding supporting careful attention to cardiovascular risk in patients with RA when evaluating treatment options.

One consideration in the use of rituximab for treatment of RA is the possibility of changing or lowering subsequent or maintenance doses. Past studies have suggested that halving the dose of rituximab to a single 1000 mg infusion was tolerated by RA patients. The REDO trial, published in 2019, looked at even lower doses: 500 mg and 200 mg. The study did not establish non-inferiority of lower doses at 6 months in a per-protocol analysis, only in intention-to-treat. An extension study of REDO presented at the ACR Convergence in 2021 looked at a subset of those patients for up to 4 years and did find non-inferiority in terms of disease activity. Wientjes et al³ present further analysis of the REDO trial with 140 RA patients at 6 months, looking at the association of rituximab dosage with B cell counts as well as the predictive value of different patient characteristics in terms of response to lower dosages. Interestingly, serum drug levels and B cell counts at 3 and 6 months did not predict response to rituximab, nor did patient characteristics, such as age, smoking, disease, duration, or seropositivity for RF and CCP. Though the authors suggest that this implies even lower doses may be effective, it is not clear, and a similar analysis of the extension trial would be of interest. 

Use of methotrexate as a first-line DMARD for RA is cost-effective but often limited by patient fears or intolerance due to adverse events (AE). This observational cohort study by Sherbini et al⁴ evaluates not only the prevalence of AE, but also baseline factors that may predict the development of AE. Over 1,000 patients with early RA initiating methotrexate were included in analysis. More than 75% reported at least one AE in 12 months, with gastrointestinal AE, such as nausea, being most prevalent (42%); 18% developed elevated liver enzyme tests (defined as a single reading above the upper limit of normal). Few strong predictors of AE were identified, though women were overall more likely than men to report AE. Reassuringly, combination conventional synthetic DMARD therapy did not generally lead to more reported AE. Given the few predictive findings from this study, analysis of a comparator group or comparison of AE at different starting and maintenance doses of methotrexate would be of interest.

References

1.  Ytterberg SR et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-326 (Jan 27).
2. Khosrow-Khavar F et al. Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study. Ann Rheum Dis. 2022 (Jan 13).
3. Wientjes MHM et al. Drug levels, anti-drug antibodies and B-cell counts were not predictive of response in rheumatoid arthritis patients on (ultra-)low-dose rituximab. Rheumatology (Oxford). 2022 (Jan 12).
4. Sherbini AA et al. Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study. Rheumatology (Oxford). 2022 (Jan 25).

Key clinical point: In patients with rheumatoid arthritis (RA), baricitinib showed better treatment responses than tumor necrosis factor (TNF) inhibitors, whereas treatment response for tofacitinib was not significantly different vs. baricitinib or biological disease-modifying antirheumatic drugs (bDMARD).

Major finding: At 1 year, TNFi vs. baricitinib showed lower European Alliance of Associations for Rheumatology (difference −4.3%; 95% CI −8.7% to 0.1%), Health Assessment Questionnaire-Disability Index improvement (difference −9.9%; 95% CI −14.4% to −5.4%), and Clinical Disease Activity Index remission (difference −6%; 95% CI −9.8% to −2.2%). Tofacitinib showed similar treatment responses vs. bDMARDs or baricitinib.

Study details: This was a nationwide cohort study involving patients with RA who initiated baricitinib (n = 1,420), tofacitinib (n = 316), abatacept (n = 1,050), interleukin-6 inhibitors (n = 849), rituximab (n = 1,101), or TNF inhibitors (n = 6,036).

Disclosures: This work was supported by the Swedish Research Council and others. J Askling, K Chatzidionysiou, and C Turesson reported receiving research grants and consulting and speaker fees from various sources. A Kastbom reported being employed by Sanofi.

Source: Barbulescu A et al. Rheumatology (Oxford). 2022 (Feb 3). Doi: 10.1093/rheumatology/keac068

Key clinical point: In patients with rheumatoid arthritis (RA), baricitinib showed better treatment responses than tumor necrosis factor (TNF) inhibitors, whereas treatment response for tofacitinib was not significantly different vs. baricitinib or biological disease-modifying antirheumatic drugs (bDMARD).

Major finding: At 1 year, TNFi vs. baricitinib showed lower European Alliance of Associations for Rheumatology (difference −4.3%; 95% CI −8.7% to 0.1%), Health Assessment Questionnaire-Disability Index improvement (difference −9.9%; 95% CI −14.4% to −5.4%), and Clinical Disease Activity Index remission (difference −6%; 95% CI −9.8% to −2.2%). Tofacitinib showed similar treatment responses vs. bDMARDs or baricitinib.

Study details: This was a nationwide cohort study involving patients with RA who initiated baricitinib (n = 1,420), tofacitinib (n = 316), abatacept (n = 1,050), interleukin-6 inhibitors (n = 849), rituximab (n = 1,101), or TNF inhibitors (n = 6,036).

Disclosures: This work was supported by the Swedish Research Council and others. J Askling, K Chatzidionysiou, and C Turesson reported receiving research grants and consulting and speaker fees from various sources. A Kastbom reported being employed by Sanofi.

Source: Barbulescu A et al. Rheumatology (Oxford). 2022 (Feb 3). Doi: 10.1093/rheumatology/keac068

Key clinical point: In patients with rheumatoid arthritis (RA), baricitinib showed better treatment responses than tumor necrosis factor (TNF) inhibitors, whereas treatment response for tofacitinib was not significantly different vs. baricitinib or biological disease-modifying antirheumatic drugs (bDMARD).

Major finding: At 1 year, TNFi vs. baricitinib showed lower European Alliance of Associations for Rheumatology (difference −4.3%; 95% CI −8.7% to 0.1%), Health Assessment Questionnaire-Disability Index improvement (difference −9.9%; 95% CI −14.4% to −5.4%), and Clinical Disease Activity Index remission (difference −6%; 95% CI −9.8% to −2.2%). Tofacitinib showed similar treatment responses vs. bDMARDs or baricitinib.

Study details: This was a nationwide cohort study involving patients with RA who initiated baricitinib (n = 1,420), tofacitinib (n = 316), abatacept (n = 1,050), interleukin-6 inhibitors (n = 849), rituximab (n = 1,101), or TNF inhibitors (n = 6,036).

Disclosures: This work was supported by the Swedish Research Council and others. J Askling, K Chatzidionysiou, and C Turesson reported receiving research grants and consulting and speaker fees from various sources. A Kastbom reported being employed by Sanofi.

Source: Barbulescu A et al. Rheumatology (Oxford). 2022 (Feb 3). Doi: 10.1093/rheumatology/keac068

Key clinical point: Vitamin D concentration at birth was not associated with the risk of developing rheumatoid arthritis (RA) in early adulthood.

Major finding: The risk of developing RA in individuals aged 18-33.9 years was not significantly different among those in the highest vs. lowest vitamin D quintile (adjusted hazard ratio 1.21; 95% CI 0.90-1.63).

Study details: This was a registry-based case-cohort study involving 805 patients with RA with onset in early adulthood and 2,416 individuals from a random subcohort.

Disclosures: This research was supported by the Danish Rheumatism Association and others. The authors declared no conflicts of interest.

Source: Cardoso I et al. Nutrients. 2022;14(3):447 (Jan 20). Doi: 10.3390/nu14030447

Key clinical point: Vitamin D concentration at birth was not associated with the risk of developing rheumatoid arthritis (RA) in early adulthood.

Major finding: The risk of developing RA in individuals aged 18-33.9 years was not significantly different among those in the highest vs. lowest vitamin D quintile (adjusted hazard ratio 1.21; 95% CI 0.90-1.63).

Study details: This was a registry-based case-cohort study involving 805 patients with RA with onset in early adulthood and 2,416 individuals from a random subcohort.

Disclosures: This research was supported by the Danish Rheumatism Association and others. The authors declared no conflicts of interest.

Source: Cardoso I et al. Nutrients. 2022;14(3):447 (Jan 20). Doi: 10.3390/nu14030447

Key clinical point: Vitamin D concentration at birth was not associated with the risk of developing rheumatoid arthritis (RA) in early adulthood.

Major finding: The risk of developing RA in individuals aged 18-33.9 years was not significantly different among those in the highest vs. lowest vitamin D quintile (adjusted hazard ratio 1.21; 95% CI 0.90-1.63).

Study details: This was a registry-based case-cohort study involving 805 patients with RA with onset in early adulthood and 2,416 individuals from a random subcohort.

Disclosures: This research was supported by the Danish Rheumatism Association and others. The authors declared no conflicts of interest.

Source: Cardoso I et al. Nutrients. 2022;14(3):447 (Jan 20). Doi: 10.3390/nu14030447

Key clinical point: In patients with rheumatoid arthritis (RA), low cumulative disease activity was associated with an increased femoral neck bone mineral density (BMD), irrespective of established osteoporosis risk factors.

Major finding: Low cumulative disease activity as measured by Disease Activity Score in 28 Joints with erythrocyte sedimentation rate was independently associated with higher femoral neck BMD compared with moderate/high disease activity (β 0.071; P = .020).

Study details: The findings come from an observational cohort study involving 161 patients with RA.

Disclosures: This study was funded by the Rheumatology Research Foundation Scientist Development Award, National Institute of Aging, and others. The authors declared no conflicts of interest.

Source: Wysham KD et al. Semin Arthritis Rheum. 2022;53:151972 (Jan 31). Doi:  10.1016/j.semarthrit.2022.151972

Key clinical point: In patients with rheumatoid arthritis (RA), low cumulative disease activity was associated with an increased femoral neck bone mineral density (BMD), irrespective of established osteoporosis risk factors.

Major finding: Low cumulative disease activity as measured by Disease Activity Score in 28 Joints with erythrocyte sedimentation rate was independently associated with higher femoral neck BMD compared with moderate/high disease activity (β 0.071; P = .020).

Study details: The findings come from an observational cohort study involving 161 patients with RA.

Disclosures: This study was funded by the Rheumatology Research Foundation Scientist Development Award, National Institute of Aging, and others. The authors declared no conflicts of interest.

Source: Wysham KD et al. Semin Arthritis Rheum. 2022;53:151972 (Jan 31). Doi:  10.1016/j.semarthrit.2022.151972

Key clinical point: In patients with rheumatoid arthritis (RA), low cumulative disease activity was associated with an increased femoral neck bone mineral density (BMD), irrespective of established osteoporosis risk factors.

Major finding: Low cumulative disease activity as measured by Disease Activity Score in 28 Joints with erythrocyte sedimentation rate was independently associated with higher femoral neck BMD compared with moderate/high disease activity (β 0.071; P = .020).

Study details: The findings come from an observational cohort study involving 161 patients with RA.

Disclosures: This study was funded by the Rheumatology Research Foundation Scientist Development Award, National Institute of Aging, and others. The authors declared no conflicts of interest.

Source: Wysham KD et al. Semin Arthritis Rheum. 2022;53:151972 (Jan 31). Doi:  10.1016/j.semarthrit.2022.151972

Key clinical point: The use of disease-modifying antirheumatic drugs (DMARD) or corticosteroids did not affect the risk for Parkinson's disease (PD) in patients with rheumatoid arthritis (RA), except for chloroquine/hydroxychloroquine, which may be potentially associated with a reduced PD risk.

Major finding: At 3 years, the use of DMARDs or corticosteroids was not associated with the risk for PD, except for chloroquine/hydroxychloroquine, which was associated with a decreased risk  (adjusted odds ratio 0.74; 95% CI 0.56-0.97).

Study details: The findings come from the nested nationwide, case-control study including 315 cases with RA diagnosed at least 3 years before the diagnosis of PD. Cases were matched to 1,571 control participants without PD but with RA.

Disclosures: The study was funded by the Michael J. Fox Foundation for Parkinson's Research. The authors declared no conflicts of interest.

Source: Paakinaho A et al. Neurology. 2022 (Jan 21). Doi: 10.1212/WNL.0000000000013303

Key clinical point: The use of disease-modifying antirheumatic drugs (DMARD) or corticosteroids did not affect the risk for Parkinson's disease (PD) in patients with rheumatoid arthritis (RA), except for chloroquine/hydroxychloroquine, which may be potentially associated with a reduced PD risk.

Major finding: At 3 years, the use of DMARDs or corticosteroids was not associated with the risk for PD, except for chloroquine/hydroxychloroquine, which was associated with a decreased risk  (adjusted odds ratio 0.74; 95% CI 0.56-0.97).

Study details: The findings come from the nested nationwide, case-control study including 315 cases with RA diagnosed at least 3 years before the diagnosis of PD. Cases were matched to 1,571 control participants without PD but with RA.

Disclosures: The study was funded by the Michael J. Fox Foundation for Parkinson's Research. The authors declared no conflicts of interest.

Source: Paakinaho A et al. Neurology. 2022 (Jan 21). Doi: 10.1212/WNL.0000000000013303

Key clinical point: The use of disease-modifying antirheumatic drugs (DMARD) or corticosteroids did not affect the risk for Parkinson's disease (PD) in patients with rheumatoid arthritis (RA), except for chloroquine/hydroxychloroquine, which may be potentially associated with a reduced PD risk.

Major finding: At 3 years, the use of DMARDs or corticosteroids was not associated with the risk for PD, except for chloroquine/hydroxychloroquine, which was associated with a decreased risk  (adjusted odds ratio 0.74; 95% CI 0.56-0.97).

Study details: The findings come from the nested nationwide, case-control study including 315 cases with RA diagnosed at least 3 years before the diagnosis of PD. Cases were matched to 1,571 control participants without PD but with RA.

Disclosures: The study was funded by the Michael J. Fox Foundation for Parkinson's Research. The authors declared no conflicts of interest.

Source: Paakinaho A et al. Neurology. 2022 (Jan 21). Doi: 10.1212/WNL.0000000000013303

Key clinical point: A healthy lifestyle was associated with a reduced risk of developing rheumatoid arthritis (RA) overall, as well as for seropositive and seronegative RA.

Major finding: Each unit increase in healthy lifestyle index score was associated with a reduced risk for overall RA (hazard ratio [HR] 0.86; P < .0001), seropositive RA (HR 0.85; P < .0001), and seronegative RA (HR 0.87; P < .001).

Study details: The findings come from an analysis of 2 large prospective cohorts including 107,092 women, among which 1,219 cases of incident RA (seropositive, 776; seronegative, 443) were identified.

Disclosures: The study was supported by the National Institutes of Health and Rheumatology Research Foundation Career Development Bridge Award. The authors declared no conflicts of interest.

Source: Hahn J et al. Arthritis Care Res (Hoboken). 2022 (Jan 18). Doi: 10.1002/acr.24862

Key clinical point: A healthy lifestyle was associated with a reduced risk of developing rheumatoid arthritis (RA) overall, as well as for seropositive and seronegative RA.

Major finding: Each unit increase in healthy lifestyle index score was associated with a reduced risk for overall RA (hazard ratio [HR] 0.86; P < .0001), seropositive RA (HR 0.85; P < .0001), and seronegative RA (HR 0.87; P < .001).

Study details: The findings come from an analysis of 2 large prospective cohorts including 107,092 women, among which 1,219 cases of incident RA (seropositive, 776; seronegative, 443) were identified.

Disclosures: The study was supported by the National Institutes of Health and Rheumatology Research Foundation Career Development Bridge Award. The authors declared no conflicts of interest.

Source: Hahn J et al. Arthritis Care Res (Hoboken). 2022 (Jan 18). Doi: 10.1002/acr.24862

Key clinical point: A healthy lifestyle was associated with a reduced risk of developing rheumatoid arthritis (RA) overall, as well as for seropositive and seronegative RA.

Major finding: Each unit increase in healthy lifestyle index score was associated with a reduced risk for overall RA (hazard ratio [HR] 0.86; P < .0001), seropositive RA (HR 0.85; P < .0001), and seronegative RA (HR 0.87; P < .001).

Study details: The findings come from an analysis of 2 large prospective cohorts including 107,092 women, among which 1,219 cases of incident RA (seropositive, 776; seronegative, 443) were identified.

Disclosures: The study was supported by the National Institutes of Health and Rheumatology Research Foundation Career Development Bridge Award. The authors declared no conflicts of interest.

Source: Hahn J et al. Arthritis Care Res (Hoboken). 2022 (Jan 18). Doi: 10.1002/acr.24862

Key clinical point: Adverse events (AE), most being nonserious, are common within the first year of treatment with methotrexate in patients with early rheumatoid arthritis (RA), with gastrointestinal AEs being most common and women more likely to report AEs compared with men.

Major finding: At least 1 AE within the first year of methotrexate initiation was reported by 77.5% of patients, with gastrointestinal AEs being the most common (42%) and nausea being the most reported single event (31.2%). Women vs. men were more likely to report gastrointestinal AEs (odds ratio 2.03; 95% CI 1.49-2.75).

Study details: The findings come from a prospective cohort of 1,069 patients with RA who initiated methotrexate therapy.

Disclosures: This work was supported by the Versus Arthritis and NIHR Manchester Biomedical Research Centre. All the authors declared no conflicts of interest.

Source: Sherbini AA et al. Rheumatology (Oxford). 2022 (Jan 25). Doi: 10.1093/rheumatology/keab917

Key clinical point: Adverse events (AE), most being nonserious, are common within the first year of treatment with methotrexate in patients with early rheumatoid arthritis (RA), with gastrointestinal AEs being most common and women more likely to report AEs compared with men.

Major finding: At least 1 AE within the first year of methotrexate initiation was reported by 77.5% of patients, with gastrointestinal AEs being the most common (42%) and nausea being the most reported single event (31.2%). Women vs. men were more likely to report gastrointestinal AEs (odds ratio 2.03; 95% CI 1.49-2.75).

Study details: The findings come from a prospective cohort of 1,069 patients with RA who initiated methotrexate therapy.

Disclosures: This work was supported by the Versus Arthritis and NIHR Manchester Biomedical Research Centre. All the authors declared no conflicts of interest.

Source: Sherbini AA et al. Rheumatology (Oxford). 2022 (Jan 25). Doi: 10.1093/rheumatology/keab917

Key clinical point: Adverse events (AE), most being nonserious, are common within the first year of treatment with methotrexate in patients with early rheumatoid arthritis (RA), with gastrointestinal AEs being most common and women more likely to report AEs compared with men.

Major finding: At least 1 AE within the first year of methotrexate initiation was reported by 77.5% of patients, with gastrointestinal AEs being the most common (42%) and nausea being the most reported single event (31.2%). Women vs. men were more likely to report gastrointestinal AEs (odds ratio 2.03; 95% CI 1.49-2.75).

Study details: The findings come from a prospective cohort of 1,069 patients with RA who initiated methotrexate therapy.

Disclosures: This work was supported by the Versus Arthritis and NIHR Manchester Biomedical Research Centre. All the authors declared no conflicts of interest.

Source: Sherbini AA et al. Rheumatology (Oxford). 2022 (Jan 25). Doi: 10.1093/rheumatology/keab917