Antibiotic Use in the 12 months Prior to Ileal Pouch-Anal Anastomosis Increases the Risk for Pouchitis

Pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), however clinical and environmental risk factors for pouchitis remain poorly understood. We explored the relationship between specific clinical factors and the incidence of pouchitis.We established a population-based cohort of all adult persons in Denmark undergoing proctocolectomy with IPAA for UC from 1996-2020. We used Cox Proportional Hazard modeling to assess the impact of antibiotic, non-steroidal anti-inflammatory drug (NSAID) exposure, and appendectomy on diagnosis of acute pouchitis in the first 2 years after IPAA surgery.Among 1,616 eligible patients, 46% developed pouchitis in the first 2 years after IPAA. Antibiotic exposure in the 12 months prior to IPAA was associated with an increased risk of pouchitis (aHR 1.41, 95% CI 1.22-1.64) after adjusting for anti-tumor necrosis factor alpha use and sex. Compared to persons without any antibiotic prescriptions in the 12 months prior to IPAA, the risk of pouchitis was increased in those with 1 or 2 courses of antibiotics in that period (aHR 1.30, 95% CI 1.11-1.52) and 3 or more courses (aHR 1.77, 95% CI 1.41-2.21). NSAID exposure in the 12 months prior to IPAA and appendectomy were not associated with risk of acute pouchitis (p=0.201 and p=0.865 respectively).In this population-based cohort study, we demonstrated that antibiotic exposure in the 12 months prior to IPAA is associated with an increased risk of acute pouchitis. Future prospective studies may isolate specific microbial changes in at-risk patients to drive earlier interventions.