Cancer risk with methotrexate-TNF antagonist combination therapy compared to TNF-antagonist monotherapy in IBD

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ID: 319992
2026
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Abstract
BACKGROUND AND AIMS: In patients with inflammatory bowel diseases (IBD), tumor necrosis factor antagonists (anti-TNFs) are frequently used alongside immunomodulators to improve treatment efficacy. While an increased risk of cancers with thiopurines is well established, there is sparse data on cancer risk with methotrexate. METHODS: We conducted a retrospective cohort study of patients with Crohn's disease (CD) or ulcerative colitis (UC) at a large, integrated healthcare system. Eligible patients received either anti-TNF monotherapy or combination (anti-TNF + methotrexate) between 1999 and 2025. The primary outcome was incident cancer confirmed by chart review. Cox-proportional hazards models were used to identify the independent effect of combination therapy on cancer risk, adjusting for relevant covariates. RESULTS: Our study included 2332 patients with IBD (80.9%) on anti-TNF monotherapy and 549 (19.1%) on combination therapy. Mean age at inclusion was 35 years, and 75.8% had CD. Mean follow-up duration was 3.3 years. Over 1353 and 8031 person-years of follow-up, incidence rates of all cancers were 7.4 and 6.4 per 1000 person-years in the combination and monotherapy groups, respectively (P = .64). We observed no increased risk of cancer between groups for all cancers (adjusted HR 0.94, 95% CI, 0.47-1.89), skin cancer (adjusted HR 0.57, 95% CI, 0.07-4.51) or non-skin cancers (adjusted HR 1.00, 95% CI, 0.48-2.11). Age ≥ 60 years and prior thiopurine exposure were associated with an increased risk of cancer. CONCLUSIONS: Combination anti-TNF and methotrexate therapy was not associated with an increased cancer risk compared to anti-TNF monotherapy in patients with IBD in our cohort.
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Authors Sama Anvari, Wasuwit Wanchaitanawong, Xin Xiong, Tianxi Cai, Ashwin N. Ananthakrishnan
Journal inflammatory bowel diseases
Year 2026
DOI
10.1093/ibd/izag143
URL
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