SummaryBackgroundEscalation to anti‐tumour necrosis factor (anti‐TNF) in inflammatory bowel disease (IBD) patients on thiopurine is a common clinical scenario. However, the impact of discontinuing thiopurine at escalation is unclear.AimTo assess the impact of discontinuing versus continuing thiopurine therapy at anti‐TNF initiation.MethodsWe used the Danish registries to establish a national cohort of patients with IBD on thiopurine therapy prior to initiating anti‐TNF from 2003 to 2018. We compared patients discontinuing thiopurine therapy within 90 days of anti‐TNF initiation to those continuing. Our primary outcome was a composite of any new oral corticosteroid use, IBD‐related hospitalization, surgery or death. We used Cox regression models to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI).ResultsOf the 10,352 anti‐TNF exposed patients, 2,630 (1590 Crohn's disease (CD) and 1040 ulcerative colitis (UC)) received thiopurines prior to anti‐TNF. After anti‐TNF initiation, 979 patients discontinued thiopurines. Discontinuing thiopurines within 90 days of anti‐TNF initiation, increased the risk of the primary outcome (aHR: 1.22; 95% CI: 1.10‐1.36), particularly for IBD‐related hospitalization (aHR: 1.14; 95% CI: 1.00‐1.31) and oral corticosteroid use (aHR: 1.27; 95% CI: 1.13‐1.44). This increased risk of the primary outcome was seen in both CD (aHR: 1.17; 95% CI 1.02‐1.34) and UC (aHR: 1.32; 95% CI: 1.12‐1.55).ConclusionsIn a nationwide cohort study of IBD patients, we observed that discontinuing thiopurines after anti‐TNF initiation was associated with an increased risk of adverse outcomes, in particular an increase in hospitalizations. Further interventional studies exploring this common clinical scenario are required.