Mucosal Healing with Vedolizumab in Patients with Chronic Pouchitis: EARNEST, a Randomized, Double-Blind, Placebo-Controlled Trial.

ABSTRACT

BACKGROUND & AIMS: Vedolizumab is indicated for the treatment of chronic pouchitis in the European Union. We assessed whether vedolizumab induced mucosal healing (MH) and if MH was associated with clinical improvements. METHODS: EARNEST, a randomized, double-blind, placebo-controlled study, evaluated vedolizumab efficacy and safety in adults with chronic pouchitis. Centrally read endoscopic and histologic evaluation was performed at baseline, Week (W)14, and W34. Ulcer count, adapted Simple Endoscopic Score for Crohn's Disease in the pouch, and Pouchitis Disease Activity Index histologic component were evaluated. Pouchitis Disease Activity Index and Inflammatory Bowel Disease Questionnaire remission at W14 and W34 were compared by MH status at W14. RESULTS: Following treatment, mean (standard deviation) number of ulcers in vedolizumab-treated patients reduced from 15.1 (16.4) to 5.0 (4.9) at W14 and 2.7 (3.2) at W34 versus placebo-treated patients with corresponding values of 11.8 (11.3), 13.4 (18.4), and 9.7 (13.8) (vedolizumab vs placebo difference [95% confidence interval] W14 -8.4 [-14.3 to -2.6]; W34 -7.0 [-12.0 to -2.0]). More patients receiving vedolizumab versus placebo achieved reduction in ulcerated pouch surface area (W14 52.4% vs 20.0%; difference, 32.4 percentage points [p.p] [9.7, 51.4]; W34 52.1% vs 12.9%; difference, 40.2p.p [15.6, 60.3]), absence of ulceration (W14 23.8% vs 7.5%; difference, 16.3p.p [1.1, 31.6]; W34 34.4% vs 15.6%; difference, 18.8p.p [-2.0, 39.5]), Simple Endoscopic Score for Crohn's Disease remission (W14 23.8% vs 7.5%; difference, 16.3p.p [1.1, 31.6]; W34 34.4% vs 15.6%; difference, 18.8p.p [-2.0, 39.5]), and MH (W14 16.7% vs 2.5%; difference, 14.2p.p [1.9, 26.4]). Patients with MH at W14 had higher rates of Pouchitis Disease Activity Index and Inflammatory Bowel Disease Questionnaire remission at W14 and W34 than those without. CONCLUSIONS: Vedolizumab induced endoscopic improvements in patients with chronic pouchitis, which was associated with improved outcomes at W34, particularly in patients achieving MH at W14. (ClinicalTrials.gov number, NCT02790138.).