Biosimilar Expansion, Lower Costs Drive Shift in RA Treatment Guidelines

The growing availability of biosimilar disease-modifying antirheumatic drugs (DMARDs) and the emergence of generic Janus kinase inhibitors (JAKi) have helped reshape how rheumatologists are advised to sequence treatments for people with rheumatoid arthritis (RA), according to updated guidance from the European Alliance of Associations for Rheumatology (EULAR).

Published in the Annals of the Rheumatic Diseases, the 2025 EULAR recommendations for the management of RA with synthetic and biologic DMARDs represent the most streamlined version of EULAR's guidance to date, consolidating 11 prior recommendations into 9.1 The update was conducted because 3 years had passed since the 2022 revision and new evidence from strategic clinical trials—as well as evolving safety data on JAKi—warranted a reassessment of the therapeutic algorithm.

A Global Task Force, A Narrower Rulebook

A 50-member international task force convened by EULAR undertook 2 systematic literature reviews (SLRs) covering efficacy and safety data published through January 2025. The group included rheumatologists from Europe, Asia, Latin America, North America, and Africa, along with patient research partners, nonphysician health professionals, and an infectious disease specialist. The steering committee first met in November 2024 in Washington, DC, with the full task force convening in Amsterdam in March 2025. Because no new DMARDs had received regulatory approval in Europe or the US since the 2022 update, the task force's primary focus was on refining therapeutic strategy and incorporating insights from newer trials.

The Biggest Break From 2022

The most consequential change in the 2025 update was the removal of prognostic risk stratification as a prerequisite for advancing to biologic DMARDs (bDMARDs) after initial methotrexate failure. Previously, the 2022 guidelines directed clinicians to assess prognostic risk factors—such as elevated autoantibody titers, early erosions, and high acute phase reactants—before deciding whether to add a bDMARD or try an additional conventional synthetic DMARD (csDMARD). The 2025 task force voted 98% in favor of eliminating that stratification step, citing evidence that people with RA who did not respond adequately to methotrexate showed limited benefit from further csDMARD cycling and that methotrexate failure itself constitutes an adverse prognostic sign.2,3

Going forward, the algorithm directs clinicians to add a bDMARD when the treatment target is not achieved with an initial csDMARD strategy, with JAKi remaining an option provided relevant risk factors—including history of major adverse cardiovascular events, malignancy, and thromboembolic events—are evaluated first. The task force voted 81% in favor of keeping JAKi safety caveats unchanged from 2022, noting that no new randomized controlled trials on cardiovascular or malignancy risk had been published since the ORAL Surveillance trial (NCT02092467) informed the prior update.4

The task force also strengthened language around DMARD continuation in sustained remission. Recommendation 9 now explicitly states that DMARDs should be continued after glucocorticoid discontinuation, with dose reduction as an option rather than cessation, given data indicating that stopping therapy leads to disease flares in the majority of people with RA.1 That change passed with 96% approval. Other recommendations retained from 2022 included the primacy of methotrexate as first-line therapy, short-term glucocorticoid bridging when initiating or changing csDMARDs (endorsed by 98% of the task force), and treat-to-target (T2T) strategies aimed at remission or low disease activity within 6 months. Levels of agreement across all 9 recommendations and 5 overarching principles exceeded a mean score of 9 out of 10—the first time in the history of these EULAR recommendations that all items achieved that threshold.

What This Means for Payers and Formulary Decisions

For managed care decision-makers, the elimination of the prognostic stratification step carries practical significance: It removes one algorithmic reason to keep people with RA on additional rounds of csDMARDs after methotrexate failure, potentially accelerating the transition to bDMARDs or JAKi. The task force pointed to the declining costs of biosimilar bDMARDs and the availability of generic tofacitinib as factors that weighed in favor of this change, reducing the cost differential that had previously supported delaying biologic initiation.

The recommendations are intended to apply broadly to adults who have received a clinical diagnosis of RA, with particular emphasis on initiating therapy as early as possible. The task force noted that these recommendations do not address people in a "pre-RA" state who have not yet developed clinical joint swelling, as trials of DMARDs in that population have demonstrated only a delay in RA classification rather than disease prevention. The guidelines also acknowledge that biosimilar and generic JAKi availability varies across countries, and that economic considerations remain relevant in less affluent health care settings.

The task force acknowledged that no new randomized controlled trial data on JAKi cardiovascular or malignancy risk were available for this update, meaning safety caveats continue to rest largely on ORAL Surveillance data and observational studies that have not consistently replicated those findings.4 The SLRs were also limited to literature published through January 2025.1

Additionally, the recommendations do not provide individualized guidance on sequencing within the bDMARD class, as head-to-head comparative efficacy data remain limited and all licensed targeted DMARDs appear broadly similar in efficacy at the group level. Predictors of individual treatment response remain an unmet need, with no validated biomarkers yet available to guide drug selection.

References

1. Smolen JS, Edwards CJ, Konzett V, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biologic disease-modifying antirheumatic drugs: 2025 update. Ann Rheum Dis. 2026;85(6):991-1009. doi:10.1016/j.ard.2026.01.023
2. van der Kooij SM, de Vries-Bouwstra JK, Goekoop-Ruiterman YP, et al. Limited efficacy of conventional DMARDs after initial methotrexate failure in patients with recent onset rheumatoid arthritis treated according to the disease activity score. Ann Rheum Dis. 2007;66(10):1356-1362. doi:10.1136/ard.2006.066662
3. Erhardt DP, Cannon GW, Teng CC, Mikuls TR, Curtis JR, Sauer BC. Low persistence rates in patients with rheumatoid arthritis treated with triple therapy and adverse drug events associated with sulfasalazine. Arthritis Care Res (Hoboken). 2019;71(10):1326-1335. doi:10.1002/acr.23759
4. Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386(4):316-326. doi:10.1056/NEJMoa2109927