Application of JAK inhibitors in the treatment of rheumatoid arthritis: a systematic analysis based on clinical trial databases and registries

Objective: To systematically analyze 2014-2025 global clinical trial data of Janus kinase (JAK) inhibitors for rheumatoid arthritis (RA), clarify their R&D evolution, regional characteristics, efficacy and safety profiles, and provide evidence-based support for optimizing RA therapeutic strategies. Methods: Trials were retrieved from 16 international registries using PubMed MeSH and Embase Emtree terms, then screened per PRISMA guidelines for compliance with 2010 ACR/EULAR RA criteria and JAK-targeted therapy. A total of 87 eligible trials were analyzed for phase, molecular target, status, drug type and geographic region. Results: < 0.01), shifting toward multi-target combinations (e.g., TYK2 + JAK1) and away from Pan-JAK agents. JAK inhibitors showed target-dependent efficacy; infections were the most common adverse events, with serious adverse event (SAE) rates of 2.91-7.37% and drug-specific safety profiles. Trial data disclosure was uneven, with gaps in investigational drug and Phase IV trial data. Conclusion: JAK inhibitors are key RA therapeutics with target-distinct efficacy and safety. Future efforts should prioritize high-quality Phase IV studies, regional subgroup analyses, head-to-head target comparisons and standardized data disclosure. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261290714, Identifier CRD420261290714.