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Updated: Jul 28, 2025
Assessing Specificity of Anticancer Drugs In Vitro
Published on: March 23, 2016
JAK inhibitors and the risk of malignancy: a meta-analysis across disease indications
Mark D Russell1, Christopher Stovin2, Edward Alveyn2
1Centre for Rheumatic Diseases, King's College London, London, UK mark.russell@kcl.ac.uk.
Objectives:
To estimate the association of Janus kinase inhibitors (JAKi) with the incidence of malignancy, compared with placebo, tumour necrosis factor (TNF)-α inhibitors (TNFi) and methotrexate.
Methods:
Systematic searches of databases were performed, to December 2022, to identify phase II/III/IV randomised clinical trials (RCTs) and long-term extension (LTE) studies of JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib) compared with placebo, TNFi or methotrexate, in adults with rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease or atopic dermatitis. Network and pairwise meta-analyses were performed to estimate incidence rate ratios (IRRs) for malignancy between JAKi and comparators. Bias was assessed using the Cochrane Risk of Bias-2 tool.
Results:
In 62 eligible RCTs and 16 LTE studies, there were 82 366 person-years of exposure to JAKi, 2924 to placebo, 7909 to TNFi and 1074 to methotrexate. The overall malignancy incidence rate was 1.15 per 100 person-years in RCTs, and 1.26 per 100 person-years across combined RCT and LTE data. In network meta-analyses, the incidence of all malignancies including non-melanomatous skin cancers (NMSCs) was not significantly different between JAKi and placebo (IRR 0.71; 95% CI 0.44 to 1.15) or between JAKi and methotrexate (IRR 0.77; 95% CI 0.35 to 1.68). Compared with TNFi, however, JAKi were associated with an increased incidence of malignancy (IRR 1.50; 95% CI 1.16 to 1.94). Findings were consistent when analysing NMSC only and when analysing combined RCT/LTE data.
Conclusions:
JAKi were associated with a higher incidence of malignancy compared with TNFi but not placebo or methotrexate. Cancers were rare events in all comparisons.
Prospero Registration Number:
CRD42022362630.
Insights
Janus kinase inhibitors (JAKi) showed a higher incidence of malignancy compared to tumor necrosis factor-alpha inhibitors (TNFi). However, JAKi were not associated with increased malignancy risk versus placebo or methotrexate. Cancers were rare overall.
Area of Science:
- Rheumatology and Immunology
- Oncology
- Pharmacovigilance
Background:
- Janus kinase inhibitors (JAKi) are used for inflammatory conditions, but their association with malignancy risk requires careful evaluation.
- Comparative safety data for JAKi against other immunomodulatory therapies are crucial for clinical decision-making.
Conclusions:
- Janus kinase inhibitors (JAKi) are associated with an increased risk of malignancy when compared to tumor necrosis factor-alpha inhibitors (TNFi).
- No significant difference in malignancy incidence was found between JAKi and placebo or methotrexate.
- These findings highlight the importance of considering comparative safety profiles when selecting treatments for inflammatory diseases.
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