{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T08:52:49Z","timestamp":1777711969463,"version":"3.51.4"},"reference-count":43,"publisher":"The Journal of Rheumatology","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>To evaluate the safety of the methotrexate (MTX)\u2013leflunomide (LEF) combination in rheumatoid arthritis (RA), comparing it with other therapeutic schemes involving conventional synthetic (cs-) and biologic (b-) disease-modifying antirheumatic drugs (DMARDs) or Janus kinase inhibitors (JAKi).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>Patients with RA starting a treatment course with a csDMARD (without previous use of bDMARD or JAKi) or their first bDMARD\/JAKi were followed up in a registry-based, multicentric cohort study in Brazil (BiobadaBrasil). The primary outcome was the incidence of serious adverse events (SAEs); secondary outcomes included serious infections. Multivariate Cox proportional hazards models and propensity score matching analysis (PSMA) were used for statistical comparisons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>In total, 1671 patients (5349 patient-years [PY]) were enrolled; 452 patients (1537 PY) received MTX + LEF. The overall incidence of SAEs was 5.6 per 100 PY. The hazard of SAEs for MTX + LEF was not higher than for MTX or LEF (adjusted HR [aHR] 1.00, 95% CI 0.76\u20131.31, <jats:italic>P<\/jats:italic> = 0.98). MTX + LEF presented a lower hazard of SAEs (aHR 0.56, 95% CI 0.36\u20130.88, <jats:italic>P<\/jats:italic> = 0.01) and infectious SAEs (aHR 0.48, 95% CI 0.25\u20130.94, <jats:italic>P<\/jats:italic> = 0.03) than bDMARDs\/JAKi with MTX or LEF. MTX + LEF presented lower hazard of SAEs than MTX + sulfasalazine (SSZ; aHR 0.33, 95% CI 0.16\u20130.65, <jats:italic>P<\/jats:italic> = 0.002). Analysis using PSMA confirmed the results obtained with traditional multivariate Cox analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion.<\/jats:title><jats:p>In our study, MTX + LEF presented a relatively good overall safety profile in comparison to MTX + SSZ and schemes involving advanced therapies in RA.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.201248","type":"journal-article","created":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T12:20:37Z","timestamp":1619871637000},"page":"1519-1527","source":"Crossref","is-referenced-by-count":13,"title":["Safety of the Methotrexate\u2013leflunomide Combination in Rheumatoid Arthritis: Results of a Multicentric, Registry-based, Cohort Study 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