OP34 VARSITY: A Double-Blind, Double-Dummy, Randomised, Controlled Trial of Vedolizumab Versus Adalimumab in Patients with Active Ulcerative Colitis

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 (n = 383) or ADA (n = 386) at 330 sites in 37 countries and received at least one dose of study drug. At Week 52, VDZ showed significantly better rates of clinical remission (primary endpoint) and mucosal healing. Overall clinical remission rates at week 52 were 31.3% (n = 120/383) for VDZ and 22.5% (n = 87/386) for ADA (P = 0.0061). Mucosal healing (Mayo endoscopic sub-score ≤1) at Week 52 was achieved in 39.7% (n = 152/383) of patients treated with VDZ and in 27.7% (n = 107/386) of patients treated with ADA (P = 0.0005). Corticosteroid-free remission rates at Week 52 showed a numerical but non-significant difference in favour of ADA. Overall, 62.7% and 69.2% of patients treated with VDZ and ADA, respectively, experienced an adverse event (AE). Serious AEs occurred in 11.0% and 13.7% of patients treated with VDZ and ADA, respectively. Exposure-adjusted rates of infections were 33.5% and 43.5% in patients treated with VDZ and ADA, respectively; few infections were considered serious in either group. 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.