EULAR Updates Therapy Recommendations for RA

EULAR published updated recommendations this month about the use of disease-modifying antirheumatic drugs (DMARDs) in individuals with rheumatoid arthritis, revisiting the last set of recommendations issued in 2019, with the major change being that Janus kinase (JAK) inhibitors should only be used if risk factors for cardiovascular disease or cancer has been considered.

This means that biologic DMARDs, irrespective of their mode of action, should be preferred over JAK inhibitors in patients with risk factors for malignancy or major adverse cardiovascular events.

The latest recommendations include 5 overarching principles and 11 recommendations on the use of DMARDs, as well as guidance on monotherapy, combination therapy, treat-to-target, and tapering strategies.

The rationale for the update, EULAR said, were 2 recent events. Earlier this year, a randomized, controlled clinical trial in patients with RA selected for various risk factors showed a higher rate of major cardiovascular events and malignancies in those receiving tofacitinib, a JAK inhibitor, compared with tumor necrosis factor inhibitors.

The study followed a 2021 FDA warning about the risks. The FDA said it “concluded there is an increased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots, and death with the arthritis and ulcerative colitis medicines Xeljanz and Xeljanz XR (tofacitinib).”

In July 2019, a previous Drug Safety Communication from the FDA showed an increased risk of blood clots and death at the higher dose of tofacitinib, based on the same trial. That came a few months after the first warning in February 2019, which warned of a higher risk of blood clots.

The warning was also extended to 2 other JAK inhibitors, baricitinib (Olumiant) and upadacitinib (Rinvoq).

The EULAR update was also based on the American College of Rheumatology recommendation discouraging the use of glucocorticoids in 2021, saying that the toxicity outweighs the benefits.

However, one minor change to the 2019 version is the recommendation to consider the addition of short-term glucocorticoids when starting or changing conventional synthetic DMARDs, but tapering and discontinuing them as quickly as possible.

Treatment must be based on shared decision making between the patient and the rheumatologist, EULAR said, accounting fordis ease activity, safety issues, and other patient factors, such as comorbidities and progression of structural damage.

The update also noted the high individual, medical, and societal costs of RA, and stressed that patients need access to multiple drugs with different modes of action to address disease heterogeneity, and they may require multiple successive therapies throughout life.

DMARD treatment should be started as soon as possible after the RA diagnosis is made, with an aim of reaching sustained remission or low disease activity, EULAR said.

The core recommendation for initial treatment with methotrexate plus glucocorticoids is retained from earlier versions. For people who have an insufficient response to this therapy within 3 to 6 months, further lines of treatment should be based on stratification according to individual risk factors, EULAR said.

This requires frequent monitoring, defined as at least every 3 months in people with active disease. Importantly, for individuals who achieve sustained remission, DMARDs may be tapered but should not be stopped.

A newly amended recommendation also outlines that only after glucocorticoids have been discontinued and a patient is in sustained remission, dose reduction of DMARDs may be considered, whether they are conventional synthetic, biologic, or targeted synthetic agents.

The updated EULAR recommendations were developed by a multidisciplinary task force of rheumatologists, other health professionals, and patient research partners, including infectious disease and epidemiology specialists. The information is based on evidence collected from 3 systematic reviews across efficacy and safety of both DMARDs and glucocorticoids.

Reference

Smolen JS, Landewé RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. Published online November 10, 2022. doi:10.1136/ard-2022-223356.