IMPACT OF ADVANCED THERAPY INITIATION ON ANTIBIOTIC DEPENDENCE IN CHRONIC POUCHITIS

Abstract INTRODUCTION About a quarter of patients with ulcerative colitis (UC) who undergo a total proctocolectomy with ileal pouch–anal anastomosis (IPAA) experience chronic pouchitis. Many such patients require frequent or long-term antibiotics hypothesized to target the microbiome. While advance therapies (AT) targeting the immune response are effective in some patients with chronic pouchitis, the impact of AT initiation on antibiotic dependence has not been robustly examined in this population. METHODS In this multicenter retrospective study, we identified adults with a diagnosis of UC who had undergone IPAA with endoscopic evidence of pouchitis either before or after AT initiation. Individuals with endoscopic findings concerning for Crohn’s-like-disease of the pouch (pre-pouch ileal inflammation or stricture, abscess, fistula, pouch stricture) or isolated cuffitis were excluded. The proportion of time on antibiotics prior to and after AT initiation was calculated over a follow-up of at least 1 year in the cohort of new AT initiators (incidence cohort). In an additional subset of prevalent AT users with chronic pouchitis, we examined frequency of antibiotic use over the first two years of follow-up. RESULTS We identified 58 individuals in the incident AT cohort and 22 individuals in the prevalent AT user cohort. Among the ATs, 38 were on TNF antagonists, 25 were on vedolizumab, and 19 were on ustekinumab. Over at least 1 year of follow-up, among those newly initiating AT, over half (59%) experienced a reduction in percentage of time on antibiotics, while 41% observed no change or higher usage (26%). The reduction group saw an absolute difference of 20% reduction in time on antibiotics. The reduction group also had a higher proportion on ustekinumab compared to the no reduction group (38% vs 8%, p = 0.014); there were no differences noted by other advanced therapies. This remained significant on multivariable analysis (aOR 8.4, p = 0.015). Other factors like history of primary sclerosing cholangitis, age at UC diagnosis or IPAA creation, and time from IPAA to initiation of AT did not predict reduction in antibiotic use after AT initiation, though male sex demonstrated a non-significant trend (aOR: 0.28, p = 0.081). DISCUSSION Almost half of patients who were started on AT for chronic pouchitis had a reduction in antibiotic use over the first 1-2 years of treatment. Disease-related parameters did not predict which patients may experience this reduction in use. Further prospective studies are needed to identify impact of AT on antibiotic use in chronic pouchitis, and to define which patients may benefit from immune-mediated versus microbiome-directed therapy.