OP34 VARSITY: A double-blind, double-dummy, randomised, controlled trial of vedolizumab versus adalimumab in patients with active ulcerative colitis
Stefan. Schreiber1, Laurent. Peyrin-Biroulet2, Edward. V. LoftusJr.3, Silvio. Danese4, Jean-Frederic. Colombel5, Brihad. Abhyankar6, Jingjing. Chen7, Raquel. Rogers7, Richard. A. Lirio7, Jeffrey. D. Bornstein7, Bruce. E. Sands5
1University-Hospital Schleswig-Holstein, Kiel, Germany, 2Nancy University Hospital, Nancy, France, 3Mayo Clinic College of Medicine, Rochester, MN, USA, 4Humanitas University, Milan, Italy, 5Icahn School of Medicine at Mount Sinai, NY, USA, 6Formerly Takeda Development Centre Europe Ltd, London, UK, 7Takeda Development Center Americas, Inc., Cambridge, MA, USA
Despite a growing number of new therapeutic options for inflammatory bowel disease (IBD), no clinical studies to date have directly compared two biologic agents. We performed a head-to-head study of the efficacy and safety of vedolizumab (VDZ) and adalimumab (ADA) for treatment over 52 weeks in adults with moderately to severely active ulcerative colitis (UC).
This was a phase 3b, double-blind, double-dummy, multi-centre, active-controlled trial enrolling patients with moderately to severely active UC (Mayo score 6 to 12 and endoscopic sub-score ≥2) who had failed other conventional therapies (NCT02497469; EudraCT 2015-000939-33). Prior tumour necrosis factor (TNF) antagonist exposure was capped at 25% of the patient population. Patients were randomised 1:1 to either: (1) active VDZ intravenous (IV) infusions (300 mg)/placebo subcutaneous (SC) injections; or (2) placebo IV infusions/active ADA SC injections (160/80/40 mg). The dosing for each active drug followed the standard, approved regimens for induction and maintenance. Dose escalation was not permitted in either group. The primary endpoint was clinical remission, defined as a complete Mayo score ≤2 with no sub-score >1 at week 52.
A total of 769 patients were randomised to VDZ (
This is the first study to directly compare two biological agents in IBD. VDZ was superior to ADA in achieving clinical remission and endoscopic mucosal healing at Week 52, while VDZ and ADA were both generally safe and well-tolerated, in patients with moderately to severely active UC.