VEDOLIZUMAB SHOWS SUPERIOR EFFICACY VERSUS ADALIMUMAB: RESULTS OF VARSITY—THE FIRST HEAD-TO-HEAD STUDY OF BIOLOGIC THERAPY FOR MODERATE-TO-SEVERE ULCERATIVE COLITIS

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 (Mayo score 6-12 and endoscopic sub-score ≥2) and had failed other conventional therapies; patients could have prior exposure to one tumour necrosis factor (TNFα) antagonist other than ADA, but enrollment was restricted to 25%. 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 favor of ADA. Minimal histologic remission with Geboes Score (<3.2) and Robarts Histopathology Index (<5) was achieved in 33.4% and 42.3% of patients treated with VDZ, respectively, compared with 13.7% and 25.6% of patients treated with ADA, respectively (p<0.0001). Clinical response at week 14 was achieved in 67.1% of patients treated with VDZ compared with 45.9% of patients treated with ADA (p<0.0001). Differences in clinical response between groups were observed early in treatment (Figure). Overall adverse event (AE) rates were generally comparable between VDZ and ADA groups (62.7%% vs 69.2%, respectively). Exposure-adjusted rates of infections were lower with VDZ (33.5%) than with ADA (43.5%), with few serious infections in either group. 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.