Efficacy and safety of upadacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis

BackgroundRheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by persistent synovial inflammation, leading to progressive joint destruction and functional impairment. Although conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), particularly methotrexate, remain the first-line therapy, a substantial proportion of patients exhibit inadequate responses and require escalation to biologic or targeted synthetic therapies.

Upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor administered orally, has demonstrated promising efficacy in phase III trials; however, a comprehensive evaluation of its dose-dependent efficacy and safety across different patient populations remains lacking.MethodsThis systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. Electronic databases, including PubMed, Web of Science, and Embase, were systematically searched from inception to July 2025 for randomized controlled trials evaluating upadacitinib in patients with RA.

The primary outcome was the proportion of patients achieving an American College of Rheumatology 20% improvement (ACR20) response at 12 weeks. Secondary outcomes included safety endpoints such as overall adverse events, serious infections, herpes zoster, and laboratory abnormalities.

Meta-analyses were performed using RevMan 5.4, with fixed- or random-effects models applied based on heterogeneity.