Short-term malignancy risk of JAK inhibitors in severe alopecia areata: a multicenter cohort study

Alopecia areata (AA) is an autoimmune hair loss disorder, with Janus kinase inhibitors (JAKis) emerging as an effective treatment. However, concerns about malignancy risk remain due to boxed warnings primarily based on studies in rheumatoid arthritis. This retrospective cohort study evaluated the association between JAKis and malignancy risk in AA using the TriNetX Global Collaborative Network. Patients with severe AA were categorized by treatment history, including JAKis, traditional immunosuppressants, and no systemic treatment. Propensity score-matched Cox proportional hazards models assessed the risks of squamous cell carcinoma (SCC)/basal cell carcinoma (BCC), internal malignancies, and hematologic malignancies. Among matched cohorts of 920 patients treated with traditional immunosuppressants and 920 treated with JAKis (mean follow-up: 1,302 and 1,229 days, respectively), SCC/BCC risk was not significantly different (HR = 0.324 [0.065, 1.609]). However, internal malignancy (HR = 4.906 [2.168, 11.101]) and hematologic malignancy (HR = 8.713 [1.104, 68.796]) risks were significantly higher with traditional immunosuppressants. No significant difference in malignancy risk was observed between 446 JAKi-treated and 446 untreated patients. These findings align with previous meta-analyses in autoimmune diseases, which have not linked JAKis to an increased malignancy risk. While this study found no evidence that JAKis elevate malignancy risk, the role of JAK-STAT signaling in cancer remains complex. Given AA's unclear baseline malignancy risk and this study's retrospective nature and limited follow-up, longer-term studies are needed to better understand the long-term safety of JAKis in AA and refine risk assessment and screening strategies.