A Phase 3 Study of Vedolizumab for Induction and Maintenance Therapy in Japanese Patients with Moderately to Severely Active Ulcerative Colitis

Background: Vedolizumab (VDZ), a monoclonal antibody that inhibits α4 β7 integrin, is approved in multiple Western countries for the treatment of ulcerative colitis (UC); however, data on its efficacy and safety are limited in Asian patients (pts). In addition, the efficacy of VDZ after 10-weeks induction has not been investigated. We performed a phase 3, multicentre, randomized, double-blind, placebo (PBO)-controlled, parallel-group study of VDZ in Japanese pts with UC (NCT02039505). Methods: Pts with moderately to severely active UC (with baseline complete Mayo score 6-12 and endoscopic subscore ≥2, who had failed existing pharmacotherapy) were enrolled into cohort 1 (C1, double-blinded) or cohort 2 (C2, open-label) in the induction phase (IP). Pts in C1 were randomized 2:1 to receive 300 mg of VDZ by intravenous infusion, or PBO, at Weeks 0, 2, 6. All pts in C2 received VDZ 300 mg at Weeks 0, 2, 6. Pts in C1 or C2 showing a clinical response to VDZ at Week 10 were enrolled into the maintenance phase (MP) at Week 14 and were randomized 1:1 to receive VDZ 300 mg or PBO (double-blinded), at Week 14 and every 8 weeks thereafter up to Week 54. The primary endpoints were clinical response rate at Week 10 for the IP (C1 only), and clinical remission rate at Week 60 for the MP. Results: A total of 292 pts were enrolled into the IP (246 pts in C1, 46 pts in C2). Baseline characteristics were comparable in all groups, except for extraintestinal manifestations, which were more frequent in the VDZ group (32.3%) compared with placebo (19.5%); 51.4% of pts had prior anti-TNFα therapy. Week 10 clinical response was achieved in 39.6% (65/164) of pts in the VDZ group and 32.9% (27/82) of pts in the PBO group; the between-group difference was not statistically significant (adjusted odds ratio [AOR]=1.37; 95% CI, 0.78-2.40; p=0.27). In the MP, clinical remission rate at Week 60 was statistically significantly superior for the VDZ group at 56.1% (23/41 pts) compared with 31.0% (13/42 pts) for the PBO group (AOR=2.88; 95% CI, 1.17-7.11; p=0.021). There were no clear differences between treatment groups in the incidence of treatment-emergent adverse events (TEAEs). Most of the TEAEs occurring in either study group, in either IP or MP, were mild to moderate in intensity. No cases of progressive multifocal leukoencephalopathy were reported and no deaths occurred during the study. Conclusions: In Japanese pts with UC, VDZ showed a numerically higher clinical response rate compared with placebo in the IP, but the difference was not statistically significant. As maintenance therapy, VDZ was significantly superior to placebo for clinical remission rate at Week 60. VDZ is safe and well-tolerated in induction and maintenance therapy for Japanese pts with UC.