Efficacy and Safety of Ustekinumab and Vedolizumab for Crohn's Disease of the Pouch

Abstract

Background and Aims Medically refractory ulcerative colitis may require colectomy with ileal pouch-anal anastomosis. Complications of the J-pouch include pouchitis, occurring in 50%-80% of patients, and Crohn's disease (CD) of the pouch, occurring in 3%-17%. Our aim was to evaluate the efficacy and safety of ustekinumab (UST) and vedolizumab (VDZ) in patients with CD of the pouch. Methods This was a retrospective, multicenter cohort study of adults with CD of the pouch treated with UST or VDZ. The primary outcome was clinical response at 3 or 6 months. Secondary outcomes included clinical remission, endoscopic response, histologic response, pouch failure or surgery, and adverse effects of therapy. Multivariable logistic regression evaluated the efficacy and safety of UST versus VDZ, adjusted for age, smoking status, disease duration, corticosteroid use, and antibiotic use. Kaplan-Meier survival analysis evaluated the durability of UST versus VDZ for CD of the pouch. Results One hundred and four patients were included in this analysis. Seventy-seven patients were treated with UST and 57 patients were treated with VDZ between 2011 and 2021. A total of 64/77 (83%) UST-treated patients and 45/57 (79%) VDZ-treated patients had prior biologic exposure. Clinical response occurred in 62% UST-treated patients and 53% VDZ-treated patients at 3 months, and in 56% and 46% at 6 months, respectively. Clinical remission occurred in 32% UST-treated patients and 18% VDZ-treated patients at 3 months and 29% and 21% at 6 months, respectively. Among those treated with UST, 41% achieved endoscopic response, 10% achieved endoscopic remission, 46% achieved histologic response, and 7% achieved histologic remission. Among those treated with VDZ, 27% achieved endoscopic response, 16% achieved endoscopic remission, 26% achieved histologic response, and 8% achieved histologic remission. Over a follow-up period of 3 years, 5% UST-treated patients had inflammatory bowel disease (IBD)-related hospitalization, and 9% required pouch-failure surgery. In total, 3% VDZ-treated patients had IBD-related hospitalization and 5% required pouch-failure surgery. Reported adverse effects were uncommon, including arthralgias (1), hair loss (1), syncope (1), and upper respiratory infection (1) for UST and wrist edema (1) and elevated transaminases (1) for VDZ. In multivariable analyses, patients on UST were more likely to have a clinical response compared to VDZ at 3 months (OR 2.73, 95% [CI] 1.13-6.56, P = .025) and 6 months (OR 2.53, 95% CI: 1.01-6.29, P = .046). UST had significantly longer durability of treatment than VDZ (log-rank P < .005). Conclusions In one of the largest cohorts evaluating UST and VDZ for CD of the pouch thus far, these biologics were found to be safe and effective treatments for CD of the pouch.