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울산대학교 의과대학, 서울아산병원

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Clin. Gastroenterol. Hepatol., Apr 28 2026, S1542-3565(26)00320-4 | https://doi.org/10.1016/j.cgh.2026.04.017 Impact of stopping thiopurines under anti-TNF therapy in inflammatory bowel disease: A population-based study

Jeongkuk Seo ^{1 †}, Seonok Kim ^{2 †}, Seung Wook Hong ³, Sung Wook Hwang ⁴, Sang Hyoung Park ⁴, Dong-Hoon Yang ³, Jeong-Sik Byeon ³, Seung-Jae Myung ³, Ye-Jee Kim ^{2 *}, Byong Duk Ye^{4 *}

¹Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
²Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
³Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
⁴Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

^†These authors contributed equally

^*Corresponding authors: correspondence to Ye-Jee Kim or Byong Duk Ye

Abstract

Background and Aims
The impact of stopping thiopurines after escalating to treatment with an anti-tumor necrosis factor (TNF) agent in patients with inflammatory bowel disease (IBD) is currently unclear. We aimed to assess the impact of stopping versus continuing thiopurines after initiating anti-TNF therapy.

Methods
In this retrospective cohort study, we analyzed data from the Korean National Health Insurance claims database of 6,235 patients with ulcerative colitis (UC) or Crohn's disease (CD) on thiopurines, who started anti-TNF treatment between 2007 and 2020. Patients were classified based on thiopurine discontinuation within 90 days of initiating anti-TNF therapy. The primary outcome was a composite of new corticosteroid use, IBD-related hospitalization, or intestinal surgery.

Results
Among the eligible patients, 1,900 (30.5%) had UC and 4,335 (69.5%) had CD; 429 (22.6%) patients with UC and 913 (21.1%) patients with CD discontinued thiopurines within 90 days. In the UC group, multivariable analysis demonstrated a modest increase in the risk of new corticosteroid use (adjusted hazard ratio [aHR], 1.18; 95% confidence interval [CI], 1.04–1.35) and the composite outcome (aHR, 1.20; 95% CI, 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 CD group. These results remained consistent in sensitivity analyses using a 6-month landmark (UC composite outcome: aHR 1.20; 95% CI 1.04–1.38).

Conclusions
Discontinuing thiopurines after initiating anti-TNF therapy was associated with a modest increase in the risk of adverse clinical events in patients with UC. This warrants careful risk–benefit assessment before stopping thiopurines after escalation to anti-TNF therapy.

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