The Risk of Lymphoma in Inflammatory Bowel Disease and its Association With Immunosuppression: A Systematic Review and Meta‐Analysis

Background and Aims There is a recognised association between inflammatory bowel disease (IBD) and lymphoma. However, the magnitude of lymphoma risk and impact of immunosuppression remain uncertain. Existing syntheses are limited by pooling of Crohn's disease (CD) and ulcerative colitis (UC) risk, conflation of disease‐ and treatment‐associated risk, and inclusion of overlapping registry populations. We aimed to evaluate the lymphoma risk in CD and UC in the published literature, including associations between immunosuppressive therapies and lymphoma. Methods Systematic review and meta‐analysis of studies published between 01/01/2000 and 20/06/2025. Lymphoma risk was evaluated through narrative synthesis and multi‐level random‐effects meta‐analysis in population‐based studies of CD and UC, and studies of immunosuppression‐associated lymphoma in IBD. Certainty of evidence was assessed using GRADE. Results Twenty‐five studies were included. Pooled relative risk of lymphoma was 3.32 (95% CI 1.80–6.13) in CD and 1.24 (95% CI 1.11–1.39) in UC. Childhood‐onset CD was associated with higher relative risk (4.23, 95% CI 2.07–8.65). Current thiopurine exposure was associated with lymphoma (RR 2.19, 95% CI 1.33–3.62) but confounding by indication limits interpretation and evidence for increasing relative risk with age is limited. Evidence for an independent association with advanced therapies was of very low certainty. Conclusions These findings support disease‐specific risk stratification for CD and UC. Future studies should investigate immunosuppression‐associated risk in CD and UC separately and we caution against overinterpretation of pooled IBD risk estimates. Current evidence supports an association between thiopurines and lymphoma but does not support an independent association with advanced therapies. Trial Registration This study was registered with PROSPERO (CRD420251027094)