OP04 Vedolizumab intravenous is effective across multiple treatment targets in chronic pouchitis: Results of the randomised, double-blind, placebo-controlled EARNEST trial

Abstract Background Pouchitis is a common complication of ileal pouch-anal anastomosis (IPAA) after proctocolectomy in ulcerative colitis (UC). There are currently no approved therapies for chronic pouchitis. Here, we report multicentre trial intravenous (IV) vedolizumab (VDZ) pouchitis IPAA patients with UC. Methods EARNEST was randomised, double-blind, placebo (PBO)-controlled, phase 4 study VDZ aged 18–80 years UC (NCT02790138). Male and female history were eligible. Patients randomised (1:1) to receive IV (300 mg) or PBO on Day 1 at Weeks (W) 2, 6, 14, 22 30, as well ciprofloxacin the first weeks. The primary endpoint modified Disease Activity Index (mPDAI) remission W14; efficacy also assessed through other mPDAI/PDAI secondary endpoints endoscopic exploratory (assessed by central reviewer) W14 W34. Safety (adverse events [AEs]) monitored throughout study. Results In total, 102 treated (51 per group). had mean age 40.8 42.9 (PBO). mPDAI rates (comprising clinical symptoms endoscopy domains) 31.4% (n=16/51) vs 9.8% (n=5/51) (p=0.013; Figure 1). Significant differences favour over seen W34, response PDAI symptoms, histology W34 (Figure rate sustained (defined both W34) higher (VDZ 27.5% [n=14/51] 5.9% [n=3/51]; difference 21.6 percentage points [95% confidence interval (CI), 6.5–37.0]) [n=16/51] 7.8% [4/51]; 23.5 CI, 8.0–38.8]). Endoscopic ulceration analysis showed greater reductions number ulcers from baseline 2). A proportion group an improved SES-CD score achieved AE similar between groups new safety signals identified (Table). Conclusion This largest double-blind PBO-controlled biologic therapy show significant benefits across multiple treatment outcomes consistent clinical, histologic endpoints, together its established profile.