Comparison of cancer risks associated with JAK inhibitors and TNF inhibitors treatment in patients with rheumatoid arthritis: a systematic review and meta-analysis of real-world cohort studies.

[INTRODUCTION] Potential increased cancer risk associated with janus kinase inhibitors (JAKi) compared with anti-tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA) remains a concern. Published cohort studies have reported conflicting results, and the discrepancies between randomized trials and real-world data remain unclear. We conducted this systematic review and meta-analysis to assess this association.

[MATERIAL/METHODS] We systematically searched PubMed, Embase and Cochrane Library for cohort studies up to January 31, 2025, comparing JAKi with TNFi and reporting cancer outcomes in RA patients. The primary outcome was overall cancer risk, and secondary outcomes included site-specific cancers. Pooled hazard ratios (HR) with 95% confidence intervals (CI) were calculated using a random-effects meta-analysis. Subgroup and sensitivity analyses were conducted to explore potential sources of heterogeneity. The certainty of evidence (CoE) were assessed using the GRADE framework.

[RESULTS] We included 5 cohort studies with 137,640 RA patients. Compared to TNFi, JAKi did not increase the risk of overall cancers (pooled HR: 1.06, 95% CI: 0.81-1.37; CoE: very low). Regarding secondary outcomes, JAKi was not linked to most cancers but increased the risk of non-melanoma skin cancer (NMSC) (HR: 1.21, 95% CI: 1.03-1.41; CoE: very low). The finding was consistent across multiple subgroup and sensitivity analyses.

[CONCLUSION] This meta-analysis found no increase in overall cancer risk with JAKi compared to TNFi, but identified an increased risk of NMSC, suggesting the need for regular dermatologic surveillance.