Appendicectomy vs JAK inhibitor therapy in biologic-refractory ulcerative colitis: a non-randomised comparison /
Eva Visser, MD PhD; Maud A Reijntjes, MD PhD; Lianne Heuthorst, MD PhD; Merle E Stellingwerf, MD PhD; Rachel West, MD PhD; Koen van Dongen, MD PhD; et al.
January 6, 2026
- The Lancet Gastroenterology & Hepatology
- The Lancet Gastroenterology & Hepatology, Volume 11, Issue 3, Pages 190–203
- 10.1016/S2468-1253(25)00291-2
Evidence before this study
We conducted a comprehensive literature search in PubMed from database inception to Dec 18, 2024, without language restrictions, using the terms: (“appendectomy”[MeSH Terms] OR “append*”[Title/Abstract]) AND (“colitis, ulcerative”[MeSH Terms] OR “ulcerative colitis”[Title/Abstract] OR “ulcerative proctocolitis”[Title/Abstract]) AND (“induction, remission”[MeSH Terms] OR “colitis, ulcerative / surgery*”). This search identified several retrospective cohort studies and a limited number of prospective observational studies suggesting potential benefit of appendicectomy in therapy-refractory ulcerative colitis, particularly proctitis. However, these studies were limited by retrospective design, small sample sizes, and heterogeneous endpoints. Importantly, no prospective studies had directly compared appendicectomy with advanced pharmacologic therapies, nor had any focused on biologic-exposed patients. Additionally, one recently published randomised controlled trial (ACCURE) examined appendicectomy for preventing relapse in patients with ulcerative colitis in remission and demonstrated a reduction in relapse rates.
Added value of this study
To our knowledge, the COSTA study is the first prospective comparative study evaluating appendicectomy against a guideline-recommended advanced therapy (JAK inhibitors) in patients with moderately to severely active ulcerative colitis who had biologic therapy failure. In a pragmatic, multicentre design using patient-preference assignment, we found significantly higher rates of clinical and corticosteroid-free remission at 12 months without therapy failure in the appendicectomy group compared with the JAK inhibitor group. This benefit extended to endoscopic outcomes, with no significant differences in serious adverse events or colectomy rates. These findings demonstrate that appendicectomy can be a safe and effective therapeutic strategy in biologic-exposed patients.
Implications of all the available evidence
When combined with previous observational data and the findings from the ACCURE trial, our study suggests that appendicectomy might alter the disease course of ulcerative colitis and offers a feasible, low-risk therapeutic option for patients with biologic therapy failure. It supports reconsideration of appendicectomy not only as an experimental option but as a potential adjunct to medical therapy in selected patients. These findings could contribute to clinical decision making and to future guideline recommendations for the management of biologic-refractory ulcerative colitis.
