• Simon Travis, Mark S Silverberg, Silvio Danese, Paolo Gionchetti, Mark Löwenberg, Vipul Jairath, Brian G Feagan, Brian Bressler, Marc Ferrante, Ailsa Hart, Dirk Lindner, Armella Escher, Stephen Jones, Bo Shen, and EARNEST Study Group.
• From the Translational Gastroenterology Unit and Kennedy Institute, National Institute for Health and Care Research Oxford Biomedical Research Centre, University of Oxford, Oxford (S.T.), and the Inflammatory Bowel Disease Unit, St. Mark's Hospital and Imperial College London, London (A.H.) - both in the United Kingdom; the Division of Gastroenterology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto (M.S.S.), the Department of Medicine, Division of Gastroenterology, Western University (V.J.), and Alimentiv (V.J., B.G.F.), London, ON, and the Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver (B.B.) - all in Canada; the Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Milan (S.D.), and the Inflammatory Bowel Disease Unit, IRCCS Azienda Ospedaliera-Universitaria di Bologna, Bologna (P.G.) - both in Italy; the Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Academic Medical Center, Amsterdam (M.L.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium (M.F.); Takeda Pharmaceuticals International, Zurich, Switzerland (D.L., A.E., S.J.); and the Interventional Inflammatory Bowel Disease Center and the Center for Ileal Pouch Disorders, Columbia University Irving Medical Center, New York-Presbyterian Hospital, New York (B.S.).
• N. Engl. J. Med. 2023 Mar 30; 388 (13): 119112001191-1200.

BackgroundApproximately half the patients with ulcerative colitis who undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) will subsequently have pouchitis, and among those patients, one fifth will have chronic pouchitis.MethodsWe conducted a phase 4, double-blind, randomized trial to evaluate vedolizumab in adult patients in whom chronic pouchitis had developed after undergoing IPAA for ulcerative colitis. Patients were assigned (in a 1:1 ratio) to receive vedolizumab intravenously at a dose of 300 mg or placebo on day 1 and at weeks 2, 6, 14, 22, and 30. All the patients received concomitant ciprofloxacin from weeks 1 to 4. The primary end point was modified Pouchitis Disease Activity Index (mPDAI)-defined remission (an mPDAI score of ≤4 and a reduction from baseline of ≥2 points in the mPDAI total score; scores range from 0 to 12, with higher scores indicating more severe pouchitis) at week 14. The mPDAI is based on clinical symptoms and endoscopic findings. Other efficacy end points included mPDAI-defined remission at week 34, mPDAI-defined response (a reduction from baseline of ≥2 points in the mPDAI score) at weeks 14 and 34, and PDAI-defined remission (a PDAI score of ≤6 and a reduction from baseline of ≥3 points; scores range from 0 to 18, with higher scores indicating more severe pouchitis) at weeks 14 and 34. The PDAI is based on clinical symptoms, endoscopic findings, and histologic findings.ResultsAmong the 102 patients who underwent randomization, the incidence of mPDAI-defined remission at week 14 was 31% (16 of 51 patients) with vedolizumab and 10% (5 of 51 patients) with placebo (difference, 21 percentage points; 95% confidence interval [CI], 5 to 38; P = 0.01). Differences in favor of vedolizumab over placebo were also seen with respect to mPDAI-defined remission at week 34 (difference, 17 percentage points; 95% CI, 0 to 35), mPDAI-defined response at week 14 (difference, 30 percentage points; 95% CI, 8 to 48) and at week 34 (difference, 22 percentage points; 95% CI, 2 to 40), and PDAI-defined remission at week 14 (difference, 25 percentage points; 95% CI, 8 to 41) and at week 34 (difference, 19 percentage points; 95% CI, 2 to 37). Serious adverse events occurred in 3 of 51 patients (6%) in the vedolizumab group and in 4 of 51 patients (8%) in the placebo group.ConclusionsTreatment with vedolizumab was more effective than placebo in inducing remission in patients who had chronic pouchitis after undergoing IPAA for ulcerative colitis. (Funded by Takeda; EARNEST ClinicalTrials.gov number, NCT02790138; EudraCT number, 2015-003472-78.).Copyright © 2023 Massachusetts Medical Society.

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