TOPLINE
JAK inhibitors were associated with a higher incidence of cancer than TNF inhibitors and standard care across immune-mediated inflammatory diseases (IMIDs).
METHODOLOGY
- Researchers conducted a systematic review and Bayesian network meta-analysis to quantify relative and absolute risks for cancer associated with JAK inhibitors vs other advanced therapies in adults with IMIDs including RA, psoriasis (PsO), psoriatic arthritis (PsA), and inflammatory bowel disease (IBD).
- A total of 305 studies (263 phase 2-4 randomized controlled trials and 42 long-term extensions) evaluating licensed doses of advanced therapies in adults with different IMIDs were included, encompassing 164,824 participants.
- Eligible treatment classes comprised TNF inhibitors, JAK inhibitors, and therapies targeting interleukin (IL)-6, CD20, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), IL-17, IL-23, and IL-12/23, with comparators including standard care (placebo or methotrexate monotherapy) or another advanced therapy.
- The primary outcome was the incidence of all malignancies including nonmelanoma skin cancer (NMSC), and the secondary outcome was the incidence of all malignancies excluding NMSC.
TAKEAWAY
- In the combined IMID network (174 studies), JAK inhibitors were associated with a higher incidence of cancer than TNF inhibitors (rate ratio [RR], 1.60; 95% credible interval [CrI], 1.27-2.02) and standard care (RR, 1.85; 95% CrI, 1.38-2.47). Under a standard background risk scenario, the estimated cancer rates were 0.06/1000 person-years exposure (PYE) for TNF inhibitors and 0.10/1000 PYE for JAK inhibitors, for an absolute difference of 0.04/1000 PYE, and under a higher background risk scenario, the rates were 11.50 and 18.40/1000 PYE, respectively.
- In RA (123 studies), JAK inhibitors were associated with an increased risk for cancer relative to TNF inhibitors (RR, 1.56; 95% CrI, 1.23-1.97), IL-6-targeting therapies (RR, 1.72; 95% CrI, 1.06-2.61), and standard care (RR, 1.66; 95% CrI, 1.19-2.28). TNF inhibitors and CD20-, CTLA-4-, and IL-6-targeting therapies showed a similar risk for cancer as standard care.
- In PsO/PsA (129 studies), JAK inhibitors were associated with a higher risk for cancer than standard care (RR, 2.62; 95% CrI, 1.01-8.02), and in IBD (54 studies), JAK inhibitors were linked to a higher risk for cancer than TNF inhibitors (RR, 3.93; 95% CrI, 1.14-14.73) and standard care (RR, 3.21; 95% CrI, 1.38-9.31).
- For the secondary outcome of total cancers excluding NMSC, JAK inhibitors were associated with a higher incidence than TNF inhibitors (RR, 1.41; 95% CrI, 1.08-1.85), with the strongest signal observed for NMSC (RR, 1.93; 95% CrI, 1.29-2.98) in exploratory subtype analyses.
IN PRACTICE
“[The study] findings provide a much-needed evidence base for the regulatory precautions currently applied to the JAKi [JAK inhibitors] class, moving beyond the observations of a single trial to a robust, cross-indication data synthesis. JAKi were consistently associated with higher malignancy risk relative to TNFi [TNF inhibitors] and SOC [standard care] across IMID networks, whereas other advanced therapy classes showed risks broadly comparable with TNFi. However, available evidence remains weighted toward tofacitinib, and formal assessment of within-class heterogeneity will require larger drug-specific datasets with longer follow-up,” the authors of the study wrote.
SOURCE
The study was led by Mark Gibson, MD, and Victoria Allen, MBBS, Centre for Rheumatic Diseases, King’s College London, London, England. It was published online on July 10, 2026, in Annals of the Rheumatic Diseases.
LIMITATIONS
Most of the trials included in the analysis were not powered to detect differences in cancer rates, and understanding specific cancer outcomes was limited for many types of cancer. Though the incorporation of long-term extension data enhanced statistical power, it might have caused bias because only certain participants continued into the extension phases. Follow-up duration was often unbalanced across different treatment groups because those in placebo or comparison groups usually discontinued or switched to active treatments during open-label extensions, which could affect relative risk estimates.
DISCLOSURES
The study did not receive any specific funding. One author reported receiving grant support from King’s College Hospital Charity and speaking and lecture fees from Novartis. Some other authors reported receiving speaking and lecture fees from various companies including Galapagos, UCB Pharma SA, Vifor Pharma Switzerland SA, Novartis, and others.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.