EULAR Updates Recommendations for Managing RA

BARCELONA, Spain — Patients with rheumatoid arthritis (RA) who have not responded to first-line methotrexate therapy should be started on a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD), according to new recommendations by the European Alliance of Associations for Rheumatology (EULAR).

These updated recommendations contain five overarching principles and nine recommendations — two fewer than those in the 2022 iteration. Several of the recommendations remain unchanged, and a few were merged or modified to provide greater clarity.

“The availability of an increasing number of good drugs and increasing evidence due to wonderful clinical trials made the task force in charge of these recommendations produce increasingly leaner recommendations,” said Josef S. Smolen, MD, of the Medical University of Vienna, Vienna, Austria, who presented them at the EULAR 2025 Annual Meeting. “It’s nice because it makes life simpler.”

EULAR continues to recommend methotrexate and short-term glucocorticoids as the first treatment strategy for RA. (In the case of contraindications, leflunomide or sulfasalazine should be considered.)

“We have yet to find something that beats methotrexate plus glucocorticoids [as a first therapy strategy],” Smolen said.

However, if the treatment target is not reached with this first conventional synthetic (cs)DMARD approach, then the patient should be started on a b/tsDMARD.

Second-Line Therapy With b/tsDMARDs

This update eliminates treatment based on stratification according to poor prognostic factors, such as the presence of autoantibodies or high disease activity. In the 2022 recommendations, patients without these factors could start another csDMARD, whereas those with these poor prognostic factors could start a b/tsDMARD.

“The task force felt that the stratification was not necessary because if you fail methotrexate plus glucocorticoids, you already have a bad prognostic sign,” Smolen explained.

Alexandre Sepriano, MD, PhD, an assistant professor of rheumatology at NOVA University Lisbon, Lisbon, Portugal, thought this change was the “most important modification” to these RA treatment guidelines and would have “significant implications for clinical practice.” He co-moderated the session where these updated recommendations were presented.

“In some countries (eg, the United Kingdom), patients previously had to fail two csDMARDs before being eligible for a biologic or JAK inhibitor,” added Kim Lauper, MD, PhD, of Geneva University Hospitals, Geneva, Switzerland, the other moderator of the session. “This new recommendation could help support policy changes that allow for earlier escalation, potentially helping more patients reach remission faster.”

EULAR still recommends that b/tsDMARDs be combined with a csDMARD. In patients who cannot use a csDMARD as a co-medication, interleukin 6 inhibitors and JAK inhibitors “may have some advantages compared with other bDMARDs,” the recommendations state.

More Research Needed on JAK Inhibitors

EULAR advises that clinicians should evaluate cardiovascular and malignancy risk factors before prescribing a JAK inhibitor. While the ORAL Surveillance trial found that the risk for major cardiovascular events and cancer was more common with tofacitinib than with TNF inhibitors, patient registries have not shown these same patterns, Smolen said. More randomized controlled trials are therefore needed to understand what could be driving the risk, he added.

“We’re awaiting more data, and we would love to see and understand the mechanisms that led to a higher incidence of malignancies and cardiovascular events [in the ORAL Surveillance trial],” he said.

Once a patient achieves sustained remission, they can taper to a lower DMARD dose; however, the new guidelines emphasize the importance of remaining on DMARDs and not stopping them entirely, Smolen said.

“Now, we more clearly state that this task force, based on newer data, felt that continuation of DMARDs — whether traditional [synthetic], biologic, or targeted synthetic DMARDs — is recommended, but dose reduction may be considered,” he continued.

Smolen reported receiving grant support from AbbVie, AstraZeneca, Galapagos, and Lilly and honoraria from Abbott, AnaptysBio, Ananda, Celltrion, Immunovant, Janssen, Lilly, Novartis-Sandoz, R-Pharma, Roche-Chugai, and UCB. Sepriano reported receiving speaking and/or consulting fees from AbbVie, Novartis, UCB, and Lilly. Lauper reported receiving speaking and/or consulting fees and/or grants from AbbVie, Novartis, Eli Lilly, Galapagos, Alfasigma, and Pfizer.