Bruce E. Sands, Laurent Peyrin-Biroulet, Edward V. Loftus Jr. Silvio Danese, Jean-Frederic Colombel, Brihad Abhyankar, Jingjing Chen, Raquel Rogers, Richard A. Lirio, Jeffrey D. Bornstein, Stefan Schreiber Stefan Schreiber will be the presenter

Affiliates

Bruce E. Sands[1]*, Laurent Peyrin-Biroulet[2], Edward V. Loftus Jr.[3], Silvio Danese[4], Jean-Frederic Colombel[1], Brihad Abhyankar[5], Jingjing Chen[6], Raquel Rogers[6], Richard A. Lirio[6] Jeffrey D. Bornstein[6], Stefan Schreiber[7]* Icahn School of Medicine at Mount Sinai, NY, USA[1], Nancy University Hospital, Nancy, France[2], Mayo Clinic College of Medicine, Rochester, MN, USA[3], Humanitas University, Milan, Italy[4], Formerly Takeda Development Centre Europe Ltd, London, UK[5], Takeda Development Center Americas, Inc., Cambridge, MA, USA[6], University-Hospital Schleswig-Holstein, Kiel, Germany[7]. * Denotes equal contributions

Abstract

Background: Biologic therapy has become an important part of the management of ulcerative colitis (UC). However, to date, there is a paucity of clinical data to inform biologic treatment options in UC. Here, we report the results of VARSITY, the first head-to-head trial comparing the efficacy and safety of two biologic therapies, vedolizumab (VDZ) vs adalimumab (ADA), in patients with moderately to severely active UC.
Methods: VARSITY was a phase 3b, randomized, double-blind, double-dummy, active-controlled study at 330 study centers in 37 countries (NCT02497469; EudraCT 2015-000939-33). Adult patients enrolled had moderately to severely active UC and had failed other conventional therapies; patients could have prior exposure to one tumour necrosis factor (TNFα) antagonist other than ADA. Patients were randomized 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). VDZ and ADA dosing followed standard approved regimens, and dose escalation was not permitted. The primary endpoint was clinical remission (complete Mayo score ≤2 with no sub-score >1) at week 52.
Results: In total, 769 patients received at least one dose of VDZ (n=383) or ADA (n=386). Baseline characteristics were generally comparable between groups. The proportion of patients achieving clinical remission at week 52 was significantly greater with VDZ (31.3%) than with ADA (22.5%; p=0.0061). Mucosal healing (Mayo endoscopic sub-score ≤1) at week 52 was achieved in significantly more patients treated with VDZ (39.7%) than ADA (27.7%; p=0.0005). Corticosteroid-free remission rates at week 52 showed a numerical but non-significant difference in favour of ADA. Differences in clinical response between groups were observed early in treatment (Figure). Overall adverse event rates were generally comparable between VDZ and ADA groups (62.7% vs 69.2%, respectively).
Conclusions: The VARSITY trial demonstrated that VDZ achieved superior clinical and endoscopic efficacy versus ADA for the treatment of moderately to severely active UC. VDZ and ADA treatment were both generally safe and well tolerated.