S1954 Impact of Proton Pump Inhibitors and NSAIDs on the Risk of Pouchitis Following Ileal Pouch-Anal Anastomosis in Ulcerative Colitis: A Propensity-Matched Cohort Study

Introduction: Up to 30% of patients with ulcerative colitis (UC) eventually require colectomy with ileal pouch-anal anastomosis (IPAA). Acute pouchitis is a common complication, affecting up to 70% of these patients. Medications such as proton pump inhibitors (PPIs) and nonsteroidal anti-inflammatory drugs (NSAIDs) have been implicated in gut microbiome alterations, potentially influencing pouchitis development. We aimed to evaluate the association between PPI vs NSAID use and the risk of pouchitis in UC patients undergoing IPAA. Methods: We conducted a retrospective cohort study using the TriNetX database, which includes de-identified electronic health records from over 125 million patients across 71 healthcare organizations in the United States. Adult UC patients who underwent IPAA were identified using International Classification of Diseases-10 codes. We included patients with documented use of PPIs or NSAIDs within 3 months post-IPAA. Propensity score matching (1:1) was applied to balance baseline characteristics between cohorts. The primary outcome was the incidence of first-time pouchitis within 2 years of surgery. Results: After matching, 1,714 patients in the PPI cohort were compared with 1,714 patients in the NSAID cohort. At 2-year follow-up, 945 patients (55.1%) in the PPI group and 990 patients (57.8%) in the NSAID group developed pouchitis. There was no statistically significant difference in the risk of pouchitis between the groups (adjusted hazard ratio [aHR]: 0.97; 95% CI: 0.84–1.00; P = 0.05). Findings were consistent across 6-month, 9-month, and 1-year follow-up intervals. However, when compared with patients who were not on PPI or NSAID, patient on PPI (aHR = 1.50; 95% CI: 1.28–1.76; P < 0.001) as well as NSAID (aHR = 1.73; 95% CI: 1.48–2.02; P < 0.001) were at higher risk of developing pouchitis. Conclusion: In this large, real-world cohort of UC patients who underwent IPAA, PPI and NSAID were associated with a significantly increased risk of developing pouchitis compared to patients who did not have exposure to any of them. These findings suggest that PPI or NSAID exposure shortly after IPAA may independently impact pouchitis risk. Further prospective studies are needed to explore the underlying mechanisms and to validate these results.