EULAR recommendations for the management of rheumatoid arthritis with synthetic and biologic disease-modifying antirheumatic drugs: 2025 update
Josef S. Smolen, Christopher J. Edwards, Victoria Konzett, Faidra Laskou, Daniel Aletaha, Roberto Caporali, Thomas Dörner, Kimme L. Hyrich, Elsa F Mateus, Janet E. Pope, Jette Primdahl, Savia de Souza, Tanja Stamm, Tsutomu Takeuchi, Désirée van der Heijde, Patrick Verschueren, Kevin L. Winthrop, Jose Maria Alvaro-Gracia, Johan Askling, Joan Bathon, Maya H. Buch, Gerd R. Burmester, Catalin Codreanu, Philip G. Conaghan, Maurizio Cutolo, Bruno Fautrel, Joao Fonseca, Laure Gossec, Espen Haavardsholm, Merete Lund Hetland, Annamaria Iagnocco, Pierre-Antonie Juge, Zhanguo Li, Rikke Helene Moe, Peter Nash, Gyula Poór, Andrea Rubbert-Roth, Raquel dos Santos Sobrin, Hendrik Schulze-Koops, Russka Shumnalieva, Ladislav Šenolt, Lucía Silva-Fernández, Anja Strangfeld, Peter Taylor, Carl Turesson, Elsa van Duuren, Maarten de Wit, Ricardo Xavier, Andreas Kerschbaumer, Robert B. M. Landewé
Abstract
OBJECTIVES: This study aims to provide an update of the European Alliance of Associations for Rheumatology (EULAR) rheumatoid arthritis (RA) management recommendations addressing the most recent insights. METHODS: An International Task Force was formed with a wide expertise and solicited 2 systemic literature research activities on the safety and efficacy of disease-modifying antirheumatic drugs (DMARDs). New evidence was discussed, considering the update from 2022. A voting process was applied to each item. Levels of evidence and strengths of recommendation were assigned, and participants voted on the levels of agreement. RESULTS: The task force agreed on 5 overarching principles and reduced the number of recommendations to 9 concerning use of conventional synthetic DMARDs (methotrexate [MTX], leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b)DMARDs (tumour necrosis factor inhibitors [adalimumab, certolizumab pegol, etanercept, golimumab, infliximab], abatacept, rituximab, tocilizumab, sarilumab, including biosimilars) and targeted synthetic [ts]DMARDs (namely the Janus kinase inhibitors [JAKi] tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target), and tapering following clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were considered. Initially, MTX ideally in combination with short-term GCs is recommended; upon insufficient response after 3 to 6 months, a bDMARD should be added; after careful consideration of risks, including MACEs, malignancies and/or thrombo-embolic events, JAKi may also be considered. If the first bDMARD (or JAKi) fails, any other bDMARD (from another or the same class) or JAKi (considering risks) is recommended. With sustained remission, DMARDs may be tapered, but caution is required as stopping often leads to a flare. Levels of evidence and levels of agreement were high for most recommendations. CONCLUSIONS: These updated EULAR recommendations provide consensus on RA management based on currently available evidence regarding efficacy, safety, and cost.