Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis

Sands BE1, Peyrin-Biroulet L1, Loftus EV Jr1, Danese S1, Colombel JF1, Törüner M1, Jonaitis L1, Abhyankar B1, Chen J1, Rogers R1, Lirio RA1, Bornstein JD1, Schreiber S1; VARSITY Study Group. N Engl J Med. 2019 Sep 26;381(13):1215-1226. doi: 10.1056/NEJMoa1905725.


Author information

From the Icahn School of Medicine at Mount Sinai, New York (B.E.S., J.-F.C.); Nancy University Hospital, Nancy, France (L.P.-B.); Mayo Clinic College of Medicine, Rochester, MN (E.V.L.); Humanitas University, Milan (S.D.); Ankara University School of Medicine, Ankara, Turkey (M.T.); Lithuanian University of Health Sciences, Kaunas, Lithuania (L.J.); Takeda Development Centre Europe, London (B.A.); Takeda Development Center Americas, Cambridge, MA (J.C., R.R., R.A.L., J.D.B.); and the University Hospital Schleswig-Holstein, Kiel, Germany (S.S.).


BACKGROUND: Biologic therapies are widely used in patients with ulcerative colitis. Head-to-head trials of these therapies in patients with inflammatory bowel disease are lacking.

METHODS: In a phase 3b, double-blind, double-dummy, randomized trial conducted at 245 centers in 34 countries, we compared vedolizumab with adalimumab in adults with moderately to severely active ulcerative colitis to determine whether vedolizumab was superior. Previous exposure to a tumor necrosis factor inhibitor other than adalimumab was allowed in up to 25% of patients. The patients were assigned to receive infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). Dose escalation was not permitted in either group. The primary outcome was clinical remission at week 52 (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). To control for type I error, efficacy outcomes were analyzed with a hierarchical testing procedure, with the variables in the following order: clinical remission, endoscopic improvement (subscore of 0 to 1 on the Mayo endoscopic component), and corticosteroid-free remission at week 52.

RESULTS: A total of 769 patients underwent randomization and received at least one dose of vedolizumab (383 patients) or adalimumab (386 patients). At week 52, clinical remission was observed in a higher percentage of patients in the vedolizumab group than in the adalimumab group (31.3% vs. 22.5%; difference, 8.8 percentage points; 95% confidence interval [CI], 2.5 to 15.0; P = 0.006), as was endoscopic improvement (39.7% vs. 27.7%; difference, 11.9 percentage points; 95% CI, 5.3 to 18.5; P<0.001). Corticosteroid-free clinical remission occurred in 12.6% of the patients in the vedolizumab group and in 21.8% in the adalimumab group (difference, -9.3 percentage points; 95% CI, -18.9 to 0.4). Exposure-adjusted incidence rates of infection were 23.4 and 34.6 events per 100 patient-years with vedolizumab and adalimumab, respectively, and the corresponding rates for serious infection were 1.6 and 2.2 events per 100 patient-years.

CONCLUSIONS: In this trial involving patients with moderately to severely active ulcerative colitis, vedolizumab was superior to adalimumab with respect to achievement of clinical remission and endoscopic improvement, but not corticosteroid-free clinical remission. (Funded by Takeda; VARSITY ClinicalTrials.gov number, NCT02497469; EudraCT number, 2015-000939-33.).

Copyright © 2019 Massachusetts Medical Society.

Comment in

© Copyright 2013-2024 GI Health Foundation. All rights reserved.
This site is maintained as an educational resource for US healthcare providers only. Use of this website is governed by the GIHF terms of use and privacy statement.