S1677 Association Between Appendectomy and Ulcerative Colitis Risk: A Real-World, Propensity-Matched Analysis From a Multicenter Cohort

Introduction: Ulcerative colitis (UC) is a chronic, immune-mediated inflammatory bowel disease (IBD) affecting the colon, with increasing prevalence worldwide. Although its pathogenesis remains incompletely understood, it is believed to result from a complex interplay of genetic, environmental, microbial, and immune factors. The role of the appendix in gut immunity and microbial homeostasis has led researchers to investigate whether appendectomy influences UC risk. While earlier studies suggested a potential protective association, results have varied, and robust evidence from large, diverse patient populations is lacking. Methods: We performed a retrospective cohort study utilizing the TriNetX US Collaborative Network, a federated database of electronic medical records from 66 healthcare organizations. We identified adults (≥18 years) with a history of appendectomy (CPT codes: 1014622, 44950, 44960, 44970) and no prior diagnosis of IBD or pregnancy. These patients were compared to a control cohort with no history of appendectomy or IBD. Propensity score matching (1:1) was used to balance demographics and comorbidities, resulting in 2 cohorts of 266,715 patients each. The primary outcome was the incidence of UC, identified using International Classification of Diseases-10 codes following the index date. Statistical analyses included risk ratio calculations and Kaplan-Meier survival analysis. Results: Post-matching, patients with prior appendectomy had a significantly lower risk of developing UC compared to the control group (4.4% vs 5.7%; Risk Ratio 0.779; 95% CI: 0.760–0.798; P < 0.001). Kaplan-Meier analysis showed a modest but statistically significant improvement in UC-free survival in the appendectomy cohort (78.54% vs 77.93%; HR 0.887, P < 0.001). Furthermore, among those who developed UC, patients in the appendectomy group had lower rates of corticosteroid use, biologic therapy escalation, and IBD-related surgeries, suggesting a milder disease course. Conclusion: In this large, real-world cohort study, prior appendectomy was associated with a statistically significant reduction in the risk of developing UC. These findings support the hypothesis that the appendix may play a role in immune regulation relevant to UC pathogenesis. While causality cannot be established, our results align with prior observational studies and underscore the need for mechanistic research into the immunologic and microbial consequences of appendectomy. Understanding these interactions may inform future strategies for UC risk prediction and prevention.