Objectives: This systematic literature review (SLR) updated evidence on the efficacy of diseasemodifying 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.Previous research questions were updated in response to these developments, and systematic literature reviews (SLRs) were conducted to collect all relevant published data.We report in this paper on the current update of the 2022 SLR on the efficacy of DMARDs and glucocorticoids (GCs) in RA 15,16, as well as additional searches on RA ILD and the prevention of RA in individuals at risk of developing the disease.The SLR on safety and disease monitoring, as well as the recommendations paper, were published separately 17,18. METHODSThe EULAR standard operating procedure for the development of recommendations and points to consider, as well as the Cochrane Handbook for SLRs and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, were adhered to in this project 19202122.The scope of the review was defined during an initial steering committee meeting held on 16 November 2024.Thirty-four research questions were defined in Population, Intervention, Comparator, Outcome (PICO) format, and a study protocol was distributed among all committee members, including a Patient Research Partner (SdS).Based on these, a literature search strategy was developed by an experienced librarian (JWS), and Medline (PubMed), Embase (OVID), The Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science, as well as conference abstracts from the 2023 and 2024 EULAR and American College of Rheumatology (ACR) annual meetings were screened without language restrictions.Hand-searched studies, as well as additional literature found through reference checking, were further included.PICO questions and the detailed search strategies are provided in the Supplementary Appendix (Section S1).For the update of the 2022 efficacy SLR 15, randomised placebo (PLC)-or active-controlled trials (RCTs) studying DMARDs or GCs in adult patients with RA and published since 14 January 2
Konzett et al. (2026) studied this question.