Konzett, Victoria, Laskou, Faidra, Smolen, Josef S, Edwards, Christopher, Aletaha, Daniel, an der Heijde, Désirée v, Winthrop, Kevin L, Takeuchi, Tsutomu, Caporali, Roberto, Verschueren, Patrick, Pope, Janet E, Hyrich, Kimme L, de Souza, Savia, Stamm, Tanja A, Primdahl, Jette, Schoones, Jan W, Landewé, Robert B M and Kerschbaumer, Andreas (2026) Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2025 update of the EULAR recommendations for the management of rheumatoid arthritis. Annals of the Rheumatic Diseases. (doi:10.1016/j.ard.2026.03.020).
Abstract
Objectives: This systematic literature review (SLR) updated evidence on the efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) to inform the 2025 update of the European Alliance of Associations for Rheumatology (EULAR) management recommendations for rheumatoid arthritis (RA).
Methods: Medline (PubMed), Embase (OVID), Cochrane Central Register of Controlled Trials, and Web of Science were searched for randomised controlled trials (RCTs) of conventional-synthetic, biological, and targeted-synthetic DMARDs (csDMARDs, bDMARDs, tsDMARDs), as well as GCs and biosimilars, published from 14 January 2022 to 22 January 2025. Additional searches on DMARDs, GCs, and antifibrotics for RA-associated interstitial lung disease (RA ILD), and on DMARDs and GCs for preventing RA in at-risk individuals, were conducted from database inception to 22 January 2025.
Results: A total of 12,567 references were identified; 390 full-texts were reviewed, and 72 studies were included. Phase 3-4 RCTs evaluated csDMARDs (hydroxychloroquine, iguratimod, leflunomide, and methotrexate), bDMARDs (abatacept, otilimab, and ozoralizumab), and tsDMARDs (ivarmacitinib, peficitinib, and tofacitinib). Twelve novel compounds were assessed in phase 2 RCTs, and 3 articles investigated GCs. Strategic trials compared conventional therapies with bDMARD- or tsDMARD-based strategies and explored precision-medicine approaches such as synovial biopsy-guided treatment and therapeutic drug monitoring. Additional evidence addressed DMARD tapering. Two RCTs assessed antifibrotics (nintedanib and pirfenidone) for RA ILD, and 7 studies evaluated DMARDs for RA prevention in at-risk populations.
Conclusions: This SLR, together with the safety review, informed the 2025 update of the EULAR RA management recommendations. Although few phase 3 trials on novel agents were available, strategic and head-to-head studies provided important insights that enabled further refinement of the established treatment algorithm.
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