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 EU. 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 histological evaluation was performed at baseline, week (W)14, and W34. Ulcer count, adapted Simple Endoscopic Score for Crohn's Disease (SES-CD) in the pouch, and Pouchitis Disease Activity Index (PDAI) histological component were evaluated. PDAI and Inflammatory Bowel Disease Questionnaire (IBDQ) remission at W14 and W34 were compared by MH status at W14. RESULTS: Following treatment, mean (SD) 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 vs 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% CI] W14-8.4 [-14.3,-2.6]; W34-7.0 [-12.0,-2.0]). More patients receiving vedolizumab vs placebo achieved reduction in ulcerated pouch surface area (W14 52.4% vs 20.0%; difference 32.4p.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]), SES-CD 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 PDAI and IBDQ remission at W14 and W34 than those without. CONCLUSION: 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.