This systematic review and Bayesian network meta-analysis evaluated relative and absolute cancer risk of JAK inhibitors (JAKis) vs other advanced therapies (TNFi, IL-6, IL-17, IL-23, IL-12/23, CTLA-4, CD20 inhibitors) across immune-mediated inflammatory diseases (RA, PsO/PsA, IBD) using 305 RCTs and long-term extension studies (164,824 participants; 264,100 person-years exposure) published up to February 2026.
JAKis were associated with higher malignancy risk than TNFi (RR 1.60; 95% CrI 1.27–2.02) and standard care (RR 1.85; 95% CrI 1.38–2.47) across all three disease areas. Absolute excess risk vs TNFi was negligible in standard-risk patients (~1 extra cancer per 27,000 person-years) but clinically meaningful in high-risk patients (~1 extra cancer per 147 person-years). IL-6, IL-17, IL-23, IL-12/23, CTLA-4, and CD20 inhibitors showed cancer risks broadly comparable to TNFi.
- Relies on RCT and long-term extension data, which may underrepresent older or higher-risk patients seen in routine care. - Class-level pooling may obscure differences between individual JAKi agents or doses. - Malignancy outcomes (including non-melanoma skin cancer) vary in ascertainment and reporting across trials.
Clinicians should apply risk-stratified decision-making when prescribing JAKis across all IMIDs—not just RA—particularly in patients with prior malignancy or other cancer risk factors. For standard-risk patients the absolute excess risk vs TNFi is very small, but it becomes meaningful in higher-risk populations (~1 extra cancer per 147 person-years).
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