Front Immunol. 2026 Jul 1;17:1784714. doi: 10.3389/fimmu.2026.1784714. eCollection 2026.
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.
PMID:42459674 | PMC:PMC13368870 | DOI:10.3389/fimmu.2026.1784714