Efficacy of DMARDs Studied to Inform 2022 EULAR Recommendations for RA Management

The efficacy of bDMARDs and tsDMARDs were studied to inform the 2022 update of the EULAR recommendations for the management of RA.

The efficacy of conventional synthetic (cs), biologic (b), and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) were determined for the treatment of rheumatoid arthritis (RA) in a review paper published in Annals of the Rheumatic Diseases. The review informed the 2022 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for the management of RA.

The Medline, EMBASE, Cochrane CENTRAL, and Web of Science databases were searched for relevant articles published in 2019 through January 14, 2022. Eligible studies had a randomized controlled trial design and investigated the efficacy of at least 1 csDMARD, bDMARD, or tsDMARD in adult patients with RA. Variables of interest included outcomes on the symptoms of RA, measures of physical functioning, patient-reported outcomes, and structural damage. Due to the heterogeneity of available study data, no meta-analysis was conducted.

Of 8969 search results, a total of 47 articles describing 38 unique trials underwent fulltext review. Studied drugs included csDMARDs such as methotrexate (MTX), leflunomide, sulfasalazine, hydroxychloroquine; bDMARDs such as abatacept, adalimumab, certolizumab-pegol, denosumab, etanercept, infliximab, levilimab, olokizumab, opineracept, rituximab, sarilumab, and tocilizumab; and tsDMARDs such as baricitinib, filgotinib, tofacitinib, and upadacitinib. Trials assessing MTX confirmed its efficacy for high-risk populations, particularly when combined with glucocorticoids. Four trials described the efficacy of olokizumab and levilimab, which are bDMARDs targeting the interleukin (IL)-6 pathway. Each of these trials demonstrated drug superiority to placebo. In patients with early RA, bDMARDs combined with MTX had comparable efficacy to csDMARDs combined with glucocorticoids.

The results of this SLR, together with one SLR on the safety of DMARDs and one on glucocorticoids, informed the taskforce of the 2022 update of the EULAR recommendations for pharmacological management of RA.

Treatment with tsDMARDs was found to be effective in multiple studies, supporting the efficacy of Janus kinase (JAK) inhibition. Patients with insufficient response to tsDMARDs responded to tumor necrosis factor inhibitors (TNFi), according to results from multiple trials. Similarly, patients with an inadequate response to upadacitinib responded to TNFi treatment if immediately switched to adalimumab. Tapering of DMARDs was feasible for some patients, who maintained low disease activity or remission while tapering therapy. Disease activity-guided tapering was recommended. Trial data did not support the use of biopsy-driven treatment allocation to tocilizumab or rituximab treatment; no clear benefit was observed over standard treatment.

“This work, together with [2] further [reviews], [1] on safety and [1] on glucocorticoid treatment informed the 2022 EULAR RA management recommendations task force with the available evidence published since 2019,” the authors of the review noted.

Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

References:

Kerschbaumer A, Sepriano A, Bergstra SA, et al. Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. Published online November 11, 2022. doi:10.1136/ard-2022-223365