Week 2 Symptomatic Response with Vedolizumab as a Predictive Factor in Japanese Anti-TNFα-Naive Patients with Ulcerative Colitis: A post hoc Analysis of a Randomized, Placebo-Controlled Phase 3 Trial

Abstract

Background and aim: To evaluate the onset of symptomatic response with vedolizumab in patients with moderate-to-severe ulcerative colitis in Japan.

Methods: Patients were randomized to receive vedolizumab 300 mg or placebo at Weeks 0, 2, and 6. Mayo subscores were analyzed in patients with baseline stool frequency (SF) ≥1 and rectal bleeding (RB) ≥1. In patients with baseline SF ≥2 and RB ≥1, the proportion who achieved SF ≤1 and RB = 0 was determined.

Results: Patients were randomized to vedolizumab (n = 164) or placebo (n = 82). Decrease from baseline in mean SF subscore was greater with vedolizumab versus placebo from Week 2 (-6.6%; 95% confidence interval [CI], -16.2, 3.0), with a greater difference in anti-tumor necrosis factor (TNF)α-naive patients (vedolizumab vs. placebo, -13.2%; 95% CI, -29.7, 3.3). Mean percentage decrease from baseline RB subscore was numerically greater with vedolizumab versus placebo from Week 6 in anti-TNFα-naive patients (-10.7%; 95% CI, -33.0, 11.5). More patients in the anti-TNFα-naive subgroup achieved SF ≤1 and RB = 0 with vedolizumab versus placebo at Week 2 (14.8%; 95% CI, 2.5, 27.0) and Week 6 (20.3%; 95% CI, 4.4, 36.2). Patients with SF ≤1 and RB = 0 at Week 2 had higher clinical response, clinical remission, and mucosal healing rates at Week 10 than those without.

Conclusions: Our results indicate that vedolizumab induces a rapid symptomatic response, particularly in anti-TNFα-naive patients, and suggest that early symptomatic improvement predicts treatment response at Week 10 (NCT02039505).

Keywords: Early symptomatic improvement; Ulcerative colitis; Vedolizumab.

Conflict of interest statement

M.N. has received honoraria from Kissei Pharma (Kissei), Takeda Pharmaceutical (Takeda), Kyorin Pharmaceutical (Kyorin), Mochida Pharmaceutical (Mochida), AbbVie GK (AbbVie), Mitsubishi Tanabe Pharma (Mitsubishi Tanabe), Nippon Kayaku, Asahi Kasei Medical (Asahi Kasei), Zeria Pharmaceutical (Zeria), Astellas Pharma (Astellas), Nichi-Iko Pharmaceutical, and Janssen Pharmaceutical (Janssen). K.W. has received honoraria and research funding from AbbVie, Mitsubishi Tanabe, EA Pharma (EA), Takeda, Kyorin, Mochida, and Janssen, and research funding from Astellas, JIMRO, Zeria, Otsuka Pharmaceutical (Otsuka), and Asahi Kasei. S.M. has received honoraria and research funding from Janssen and Takeda; honoraria from Mitsubishi Tanabe and Mochida; and research funding from Pfizer Japan (Pfizer). H.O. has received honoraria from Takeda and research funding from Mitsubishi Tanabe, Mochida, Pfizer, and AbbVie. T.K. has received honoraria and research funding from Mitsubishi Tanabe, Miyarisan Pharmaceutical (Miyarisan), and Takeda; honoraria from Astellas and AstraZeneca; and research funding from EN Otsuka, Ezaki Glico, Otsuka, AbbVie, Mochida, Kyorin, Daiichi Sankyo, Nippon Kayaku, Yakult, Zeria, Sumitomo Dainippon Pharma, Ono Pharmaceutical, EA, Eisai, JIMRO, Chugai Pharmaceutical (Chugai), and UCB Japan (UCB). T.M. has received honoraria and research funding from EA, Ajinomoto Seiyaku (Ajinomoto), AbbVie, Eisai, Kyorin, Zeria, Takeda, Mitsubishi Tanabe, and Mochida; research funding from Miyarisan, Otsuka, Asahi Kasei, Astellas, AstraZeneca, MSD, JIMRO, Taiho Pharmaceutical (Taiho), Daiichi Sankyo, Nippon Kayaku, Kyowa Hakko Kirin, UCB, and Chugai. Y.S. has received honoraria and research funding from Mitsubishi Tanabe, AbbVie, EA, and Mochida; honoraria from Janssen, Zeria, and Kyorin; and research funding from JIMRO, Kissei, and Nippon Kayaku. P.P., L.U., S.S., M.S., T.H., and J.F. are employees of Takeda. T.H. has received honoraria and research funding from AbbVie, JIMRO, and Zeria; honoraria from Takeda, Mitsubishi Tanabe, Aspen Japan, Ferring, Gilead Sciences, Kissei, Mochida, Nippon Kayaku, Janssen, and Pfizer; and research funding from EA and Otsuka. M.W. has received honoraria and research funding from Mitsubishi Tanabe, Takeda, EA, Zeria, and Gilead Sciences; honoraria from Ajinomoto, Janssen, Celltrion Healthcare, and Pfizer; and research funding from Nippon Kayaku, Mochida, Kissei, Miyarisan, Asahi Kasei, JIMRO, Kyorin, AbbVie, Kyowa Hakko Kirin, Kaken Pharmaceutical, Alfresa Pharma, Ayumi Pharmaceutical, Astellas, MSD, Daiichi Sankyo, Taiho, Toray Industries, Chugai, and Fujirebio.

The Author(s). Published by S. Karger AG, Basel.

Figures

Fig. 1

Percentage change from baseline in Mayo SF subscore by visit (patients with SF subscore ≥1 at baseline) in overall population (a), anti-TNFα-naive patients (b), anti-TNFα-exposed patients (c), baseline full Mayo score 6–8 (d), and baseline full Mayo score 9–12 (e). CI, confidence interval; PBO, placebo; SD, standard deviation; SF, stool frequency; TNFα, tumor necrosis factor alpha; VDZ, vedolizumab.

Fig. 2

Percentage change from baseline in Mayo RB subscore by visit (patients with RB subscore ≥1 at baseline) in overall population (a), anti-TNFα-naive patients (b), anti-TNFα-exposed patients (c), baseline full Mayo score 6–8 (d), and baseline full Mayo score 9–12 (e). CI, confidence interval; PBO, placebo; RB, rectal bleeding; SD, standard deviation; TNFα, tumor necrosis factor alpha; VDZ, vedolizumab.

Fig. 3

Proportion of patients (with Mayo SF subscore ≥2 and RB subscore ≥1 at baseline) who achieved Mayo SF subscore ≤1 and RB subscore = 0, by visit in overall population (a), anti-TNFα-naive patients (b), anti-TNFα-exposed patients (c), baseline full Mayo score 6–8 (d), and baseline full Mayo score 9–12 (e). CI, confidence interval; PBO, placebo; RB, rectal bleeding; SF, stool frequency; TNFα, tumor necrosis factor alpha; VDZ, vedolizumab.