Impact of Stopping Thiopurines Under Anti–Tumor Necrosis Factor Therapy in Inflammatory Bowel Disease: A Population-Based Study

초록

Background & Aims The impact of stopping thiopurines after escalating to treatment with an anti–tumor necrosis factor agent in patients with inflammatory bowel disease is currently unclear. We aimed to assess the impact of stopping vs continuing thiopurines after initiating anti–tumor necrosis factor therapy. Methods In this retrospective cohort study, we analyzed data from the Korean National Health Insurance claims database of 6235 patients with ulcerative colitis or Crohn’s disease on thiopurines, who started anti–tumor necrosis factor treatment between 2007 and 2020. Patients were classified based on thiopurine discontinuation within 90 days of initiating anti–tumor necrosis factor therapy. The primary outcome was a composite of new corticosteroid use, inflammatory bowel disease–related hospitalization, or intestinal surgery. Results Among the eligible patients, 1900 (30.5%) had ulcerative colitis, and 4335 (69.5%) had Crohn’s disease; 429 (22.6%) patients with ulcerative colitis and 913 (21.1%) patients with Crohn’s disease discontinued thiopurines within 90 days. In the ulcerative colitis group, multivariable analysis demonstrated a modest increase in the risk of new corticosteroid use (adjusted hazard ratio, 1.18; 95% confidence interval, 1.04–1.35) and the composite outcome (adjusted hazard ratio, 1.20; 95% confidence interval, 1.05–1.37) among patients who discontinued thiopurines. In contrast, no independent association was observed between thiopurine discontinuation and adverse clinical outcomes in the Crohn’s disease group. These results remained consistent in sensitivity analyses using a 6-month landmark (ulcerative colitis composite outcome: adjusted hazard ratio, 1.20; 95% confidence interval, 1.04–1.38). Conclusions Discontinuing thiopurines after initiating anti–tumor necrosis factor therapy was associated with a modest increase in the risk of adverse clinical events in patients with ulcerative colitis. This warrants careful risk–benefit assessment before stopping thiopurines after escalation to anti–tumor necrosis factor therapy.

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