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

Abstract

<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>China (42 trials) and the U.S. (32 trials) dominated global research, with the U.S. leading R&D and China combining independent and collaborative studies. JAK2/JAK3-targeted trials rose from 25% (2014-2018) to 62.7% (2019-2025, <i>p</i> < 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.<h4>Conclusion</h4>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.<h4>Systematic review registration</h4>https://www.crd.york.ac.uk/PROSPERO/view/CRD420261290714, Identifier CRD420261290714.