JAK inhibitors in rheumatoid arthritis-associated interstitial lung disease: a review of mechanisms and clinical evidence
In brief
JAK inhibitors stabilize lung function in RA-ILD without increasing new ILD risk
Observational data and meta-analyses show that oral JAK inhibitors do not raise the incidence of interstitial lung disease in rheumatoid arthritis patients and appear to halt or improve lung function and imaging findings, performing similarly to abatacept or rituximab. However, real-world reports suggest higher mortality and severe events versus TNF inhibitors, especially in older or cardiovascularly compromised patients, so careful selection is essential.
- Journal
- Frontiers in immunology (Q1)
- Published
- 1 July 2026
- Study design
- Narrative review / expert opinion
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Zhiying Wu, Li Jiang, Xu Zheng, Wanlin Zhou, Zuofeng Wang, Weilin Xie
- PMID
- 42459674
- DOI
- 10.3389/fimmu.2026.1784714
Why clinicians should know about it
- Picked for Rheumatology (top studies of the week, 19 July 2026): JAK inhibitors may stabilize RA‑associated interstitial lung disease
Abstract
Janus kinase (JAK) inhibitors, as oral targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs), represent a promising therapeutic option for rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Preclinical studies suggest a dual mechanism, inhibiting the pro-fibrotic interleukin-17A (IL-17A)/JAK2/nuclear factor kappa B (NF-κB) axis in lung fibroblasts and modulating lung immunity. Clinical evidence, primarily from observational studies and meta-analyses, indicates that JAK inhibitors do not increase the risk of incident ILD and may stabilize or improve lung function and radiological findings in established RA-ILD, showing comparable efficacy to abatacept or rituximab. However, recent real-world data highlight potential safety concerns, suggesting a higher risk of mortality and severe outcomes compared to tumor necrosis factor (TNF) inhibitors, particularly in older patients or those with cardiovascular comorbidities. While effective, the use of JAK inhibitors in RA-ILD requires careful patient selection and risk-benefit assessment, underscoring the need for confirmatory randomized controlled trials.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.