Comparative Risk of Cancer with non-TNF Advanced Therapies Versus Anti-TNF Therapy in Inflammatory Bowel Disease

BACKGROUND: Safety is important when selecting advanced therapies for inflammatory bowel disease (IBD). Safety data for anti-interleukin therapy (anti-IL) or vedolizumab come from trials with limited follow-up, and direct comparisons with anti-tumor necrosis factors (anti-TNFs) for incident cancer are lacking. We evaluated cancer incidence in patients with IBD treated with anti-IL therapy or vedolizumab versus anti-TNFs. METHODS: We conducted a retrospective cohort study of adults with IBD and no prior cancer who initiated anti-IL therapy, vedolizumab or anti-TNFs. Our primary outcome was incident cancer from 90 days after therapy initiation through discontinuation. We calculated incidence rates and performed Cox proportional hazards models. RESULTS: We identified 4,019 advanced therapy starts: 995 anti-IL, 692 vedolizumab, and 2,332 anti-TNF starts, with mean therapy duration of 1096 days. In multivariable analysis, there was a trend towards a lower hazard of all cancers among anti-IL users compared to anti-TNF users (HR 0.47; 95% CI 0.21-1.04), which was significant on sensitivity analyses. There was no difference in hazard of skin cancers (HR 1.56; 95% CI 0.39-6.15); however, the hazard of non-skin cancer was significantly lower among anti-IL users compared to anti-TNF users (HR 0.28; 95% CI 0.09-0.81). When comparing vedolizumab to anti-TNFs, there was no significant difference in the hazard of all cancer (HR 0.52, 95% CI 0.24-1.12) and non-skin cancer (HR 0.63, 95% CI 0.29-1.39). CONCLUSIONS: We found no evidence of an increased cancer risk with anti-IL therapy compared with anti-TNF therapy in patients with IBD. There was no difference in the cancer risk between vedolizumab and anti-TNF therapy.