Effects of vedolizumab in Japanese patients with Crohn’s disease: a prospective, multicenter, randomized, placebo-controlled Phase 3 trial with exploratory analyses

BACKGROUND: Vedolizumab is a gut-selective humanized antibody that binds the α(4)β(7) integrin. We evaluated efficacy and safety of vedolizumab in Japanese patients with moderate-to-severe Crohn’s disease (CD). METHODS: In this Phase 3, double-blind study (NCT02038920), 157 patients were randomized to receive intravenous vedolizumab 300 mg (n = 79) or placebo (n = 78) at Weeks 0, 2, and 6 (induction phase). Patients with CD activity index (CDAI)-70 response at Week 10 were randomized to receive vedolizumab 300 mg (n = 12) or placebo (n = 12) at Week 14, then every 8 weeks until Week 54 (maintenance phase). Primary endpoints were ≥ 100-point reduction in CDAI (CDAI-100 response) at Week 10 for induction, and clinical remission (CR: CDAI ≤ 150) at Week 60 for maintenance. RESULTS: At Week 10, 26.6% of patients who received vedolizumab and 16.7% who received placebo achieved CDAI-100 response (odds ratio [OR] [95% confidence interval (CI)] 1.80 [0.82–3.96]; p = 0.145). At Week 60, 41.7% of vedolizumab-treated patients and 16.7% of placebo-treated patients achieved CR (OR [95% CI] 3.57 [0.53–23.95]; p = 0.178). The incidence of adverse events was similar in both treatment groups in both induction and maintenance phases. In patients without prior anti-TNFα exposure or with inadequate response to anti-TNFα, vedolizumab showed improved outcomes over placebo in the induction phase. Age might be a possible predictive factor of CR for future research. CONCLUSION: Vedolizumab showed a numerically greater efficacy versus placebo as induction therapy, but the difference was not statistically significant. Vedolizumab also showed a numerically greater efficacy in maintenance therapy, and was well tolerated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00535-019-01647-w) contains supplementary material, which is available to authorized users.