SYSTEMATIC REVIEW article
Front. Med.
Sec. Rheumatology
Application of JAK Inhibitors in the Treatment of Rheumatoid Arthritis: A Systematic Analysis Based on Clinical Trial Databases and Registries
Junjie Cao 1
Rong Huang 1
Yanru Chen 1
Xu Li 1
Junyi Lou 1
Longyuan Xu 1
Junxian Gu 1
Zining Luo 2
Tianliang Yao 3
Jiebin Xie 4
1. North Sichuan Medical College, Nanchong, China
2. North Sichuan Medical University Department of Biochemistry, Nanchong, China
3. The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR China
4. Affiliated Hospital of North Sichuan Medical College, Nanchong, China
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Abstract
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 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, p<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.
Summary
Keywords
biological disease-modifying antirheumatic drugs, clinical trials, efficacy and safety, Janus kinase inhibitors, Rheumatoid arthritis
Received
22 August 2025
Accepted
11 February 2026
Copyright
© 2026 Cao, Huang, Chen, Li, Lou, Xu, Gu, Luo, Yao and Xie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jiebin Xie
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