Cancer Risk in IBD Patients Treated with Thiopurines or Anti-TNF-α Therapy: A Meta- analysis of Population-Based Studies

Objective To evaluate the cancer risk in patients with IBD treated with thiopurines or anti-tumor necrosis factor-α (anti-TNF-α) therapy through a meta-analysis. Methods A systematic search of PubMed, Embase, and Web of Science identified 31 population-based cohort studies (718,472 IBD patients). Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Subgroup analyses (Crohn’s disease [CD] vs. ulcerative colitis [UC]), sensitivity analyses, and publication bias assessments were performed. Results Thiopurine use significantly increased the risk of overall malignancies (HR = 1.53, 95% CI:1.06–2.2), particularly melanoma (HR = 2.7, 1.91–3.83) and lymphoma (HR = 1.64, 1.33–2.02). Subgroup analyses revealed higher risks in CD than UC patients (lymphoma: HR = 2.00 vs. 1.75). Conversely, thiopurines were associated with a potential reduction in colorectal cancer risk (HR = 0.56, 0.32–0.99), though this did not reach statistical significance ( P  = 0.234). Anti-TNF-α monotherapy showed no significant overall cancer risk, but combination therapy with thiopurines elevated lymphoma risk (HR = 3.7). Limited evidence suggested associations with urinary tract (HR = 2.82, 1.04–7.68) and hematologic cancers (HR = 2.41, 1.04–4.76). Conclusion Thiopurines are linked to increased risks of specific cancers but may mitigate colorectal cancer risk via anti-inflammatory effects. Clinicians should balance immunosuppressive benefits against oncological risks and enhance cancer surveillance in long-term users. Future studies should explore dose-response relationships and safety profiles of newer biologics.