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

**Authors:** Junjie Cao, Rong Huang, Yanru Chen, Xu Li, Junyi Lou, Longyun Xu, Junxian Gu, Zining Luo, Tianliang Yao, Jiebin Xie

PMC · DOI: 10.3389/fmed.2026.1680115 · 2026-03-05

## TL;DR

This paper analyzes global clinical trial data on JAK inhibitors for rheumatoid arthritis from 2014 to 2025, highlighting trends in research, efficacy, and safety.

## Contribution

The study provides a systematic global analysis of JAK inhibitor trials for RA, revealing shifts in target preferences and regional research patterns.

## Key findings

- China and the U.S. led JAK inhibitor RA trials, with China combining independent and collaborative studies.
- Trials targeting JAK2/JAK3 increased significantly from 25% (2014–2018) to 62.7% (2019–2025).
- Infections were the most common adverse events, with SAE rates ranging from 2.91–7.37%.

## Abstract

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.

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.

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.

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.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420261290714, Identifier CRD420261290714.

## Linked entities

- **Proteins:** jak (Janus kinase), JAK2 (Janus kinase 2), JAK3 (Janus kinase 3), TYK2 (tyrosine kinase 2), JAK1 (Janus kinase 1)
- **Diseases:** rheumatoid arthritis (MONDO:0008383)

## Full-text entities

- **Genes:** JAK3 (Janus kinase 3) [NCBI Gene 3718] {aka JAK-3, JAK3_HUMAN, JAKL, L-JAK, LJAK}, JAK1 (Janus kinase 1) [NCBI Gene 3716] {aka AIIDE, JAK1A, JAK1B, JTK3}, JAK2 (Janus kinase 2) [NCBI Gene 3717] {aka JTK10}, TYK2 (tyrosine kinase 2) [NCBI Gene 7297] {aka IMD35, JTK1}
- **Diseases:** RA (MESH:D001172), infections (MESH:D007239)
- **Chemicals:** inhibitors (-)

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12999776/full.md

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Source: https://tomesphere.com/paper/PMC12999776