Vedolizumab in Japanese patients with ulcerative colitis: A Phase 3, randomized, double-blind, placebo-controlled study

Satoshi Motoya, Kenji Watanabe, Haruhiko Ogata, Takanori Kanai, Toshiyuki Matsui, Yasuo Suzuki, Mitsuhiro Shikamura, Kenkichi Sugiura, Kazunori Oda, Tetsuharu Hori, Takahiro Araki, Mamoru Watanabe, Toshifumi Hibi, Satoshi Motoya, Kenji Watanabe, Haruhiko Ogata, Takanori Kanai, Toshiyuki Matsui, Yasuo Suzuki, Mitsuhiro Shikamura, Kenkichi Sugiura, Kazunori Oda, Tetsuharu Hori, Takahiro Araki, Mamoru Watanabe, Toshifumi Hibi

Abstract

Background: Vedolizumab safety and efficacy have been established in many populations all over the world, but have never been studied in Japan. We report results from a Phase 3, randomized, double-blind, placebo-controlled study of vedolizumab in Japanese patients with active ulcerative colitis (UC).

Methods: Patients with moderate-to-severe UC were enrolled into Cohort 1 (double-blinded) or Cohort 2 (open-label) in the induction phase. Cohort 1 was randomized 2:1 to receive 300 mg vedolizumab or placebo, while Cohort 2 received vedolizumab 300 mg only, at Weeks 0, 2, and 6. Patients from Cohorts 1 and 2 showing a clinical response to vedolizumab at Week 10 were randomized 1:1 to receive vedolizumab or placebo (double-blinded) at Week 14 and then every 8 weeks up to Week 54 as the maintenance phase. The primary endpoint was clinical response at Week 10, for the induction phase, and clinical remission at Week 60, for the maintenance phase.

Results: A total of 292 patients were enrolled into the induction phase (246 in Cohort 1, 46 in Cohort 2); 83 patients achieved response to vedolizumab and were subsequently enrolled into the maintenance phase. Clinical response rates at Week 10 were 39.6% (65/164) and 32.9% (27/82) in the vedolizumab and placebo groups in Cohort 1, respectively (adjusted odds ratio [AOR] = 1.37, 95% CI 0.779-2.399; p = 0.2722). In the maintenance phase, clinical remission rate at Week 60 was significantly higher in the vedolizumab group, at 56.1% (23/41), versus 31.0% (13/42) for placebo (AOR = 2.88, 95% CI 1.168-7.108; p = 0.0210). Most adverse events were mild to moderate in intensity, and no deaths occurred during the study period.

Conclusions: Vedolizumab showed numerically greater efficacy compared with placebo as induction therapy, but the difference was not statistically significant. Vedolizumab was significantly superior to placebo as maintenance therapy in Japanese patients with UC. Vedolizumab has favourable safety and tolerability in these patients.

Trial registration: ClinicalTrials.gov: NCT02039505.

Conflict of interest statement

Satoshi Motoya has received honoraria from Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. Ltd., Janssen Pharmaceutical K.K., and Takeda Pharmaceutical Co. Ltd.; and has received research grants from Pfizer Japan Inc., Janssen Pharmaceutical K.K., and from Takeda Pharmaceutical Co. Ltd. Kenji Watanabe has received honoraria from AbbVie GK, Mitsubishi Tanabe Pharma Corporation, EA Pharma Co. Ltd., Takeda Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mochida Pharmaceutical Co. Ltd. and Janssen Pharmaceutical K.K.; has received research grants from EA Pharma Co. Ltd. and Takeda Pharmaceutical Co. Ltd.; has received scholarship grants from Astellas Pharma Inc., EA Pharma Co. Ltd., Takeda Pharmaceutical Co. Ltd., AbbVie GK, Kyorin Pharmaceutical Co. Ltd. and JIMRO Co. Ltd.; and was a recipient of endowed chairs funded by AbbVie GK, EA Pharma Co. Ltd., Zeria Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, JIMRO Co. Ltd., Otsuka Pharmaceutical Co. Ltd., Asahi Kasei Medical Co. Ltd. and Mochida Pharmaceutical Co. Ltd. Haruhiko Ogata has received honoraria from Takeda Pharmaceutical Co. Ltd.; and has received scholarship grants from Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. Ltd. and Pfizer Japan Inc. Takanori Kanai has received honoraria Mitsubishi Tanabe Pharma Corporation, Astellas Pharma Inc., Miyarisan Pharmaceutical Co. Ltd., AstraZeneca K.K. and Takeda Pharmaceutical Co. Ltd.; has received research grants from EN Otsuka Pharmaceutical Co. Ltd, Miyarisan Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Ezaki Glico Co. Ltd., Otsuka Pharmaceutical Co. Ltd. and Mitsubishi Tanabe Pharma Corporation; has received scholarship grants from AbbVie GK, Mochida Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Yakult Honsha Co. Ltd., Zeria Pharmaceutical Co. Ltd., Sumitomo Dainippon Pharma Co. Ltd., Ono Pharmaceutical Co. Ltd., EA Pharma Co. Ltd., Eisai Co. Ltd. and JIMRO Co. Ltd.; and was a recipient of endowed chairs funded by Chugai Pharmaceutical Co. Ltd., AbbVie GK, UCB Japan Co. Ltd., Mitsubishi Tanabe Pharma Corporation, EA Pharma Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Zeria Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., JIMRO Co. Ltd. and Mochida Pharmaceutical Co. Ltd. Toshiyuki Matsui has received honoraria from EA Pharma Co. Ltd., Ajinomoto Seiyaku, Abbvie GK, Eisai Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Zeria Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. Ltd. and Janssen Pharmaceutical K.K.; has received research grants from Takeda Pharmaceutical Co. Ltd., Miyarisan Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation and Otsuka Pharmaceutical Co. Ltd.; has received scholarship grants from Abbvie GK, Asahi Kasei Medical Co. Ltd., Astellas Pharma Inc., AstraZeneca K.K., EA Pharma Co. Ltd., Eisai Co. Ltd., MSD K.K., Otsuka Pharmaceutical Co. Ltd., JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Takeda Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Nippon Kayaku Co. Ltd. and Mochida Pharmaceutical Co. Ltd.; and was a recipient of endowed chairs funded by AbbVie GK, Asahi Kasei Medical Co. Ltd., Ajinomoto Seiyaku, Inflammatory Bowel Disease Advanced Clinical Treatment endowed chair, Regional/Emergency Medical Management endowed chair (Fukuoka), Eisai Co. Ltd., Otsuka Pharmaceutical Co. Ltd., Kyowa Hakko Kirin Co. Ltd., Kyorin Pharmaceutical Co. Ltd., JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, UCB Japan Co. Ltd., EA Pharma Co. Ltd., Mochida Pharmaceutical Co. Ltd. and Chugai Pharmaceutical Co. Ltd. Yasuo Suzuki has received honoraria from Takeda Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, AbbVie GK, EA Pharma Co. Ltd., Zeria Pharmaceutical Co. Ltd., Mochida Pharmaceutical Co. Ltd. and Kyorin Pharmaceutical Co. Ltd.; and has received scholarship grants from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, EA Pharma Co. Ltd., JIMRO Co. Ltd., Mochida Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd. and Kissei Pharmaceutical Co. Ltd. Mitsuhiro Shikamura, Kenkichi Sugiura, Kazunori Oda, Tetsuharu Hori, and Takahiro Araki are employees of Takeda Pharmaceutical Co. Ltd. Mamoru Watanabe has received honoraria from Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co. Ltd., EA Pharma Co. Ltd., Zeria Pharmaceutical Co. Ltd., Ajinomoto Seiyaku, and Eisai Co. Ltd.; has received research grants from Kaken Pharmaceutical Co. Ltd., Alfresa Pharma Corporation and Eisai Co. Ltd.; has received scholarship grants from EA Pharma Co. Ltd., Zeria Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Astellas Pharma Inc., MSD K.K., Daiichi Sankyo Co. Ltd., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Mochida Pharmaceutical Co. Ltd., Ayumi Pharmaceutical Corporation, Kissei Pharmaceutical Co. Ltd. and Miyarisan Pharmaceutical Co. Ltd.; and was a recipient of endowed chairs funded by Asahi Kasei Medical Co. Ltd., EA Pharma Co. Ltd., JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Kyorin Pharmaceutical Co. Ltd., AbbVie GK, Kyowa Hakko Kirin Co. Ltd., MSD K.K., Toray Industries, Inc., Chugai Pharmaceutical Co. Ltd., Gilead Sciences, Inc. and Fujirebio Inc. Toshifumi Hibi has received honoraria from Takeda Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, AbbVie GK, Zeria Pharmaceutical Co. Ltd., JIMRO Co. Ltd., EA Pharma Co. Ltd., Janssen Pharmaceutical K.K. and Pfizer Japan Inc.; has received scholarship grants from EA Pharma Co. Ltd., Nippon Kayaku Co. Ltd., Zeria Pharmaceutical Co. Ltd. and Mochida Pharmaceutical Co. Ltd.; and was a recipient of endowed chairs funded by Otsuka Holdings Co. Ltd., AbbVie GK, JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd. and EA Pharma Co. Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Patient disposition.
Fig 1. Patient disposition.
Baseline characteristics were generally similar across all groups. However, patients with C-reactive protein (CRP) levels ≥3 mg/L were more frequent in the vedolizumab group compared with placebo, especially those with prior anti-TNF exposure, indicating a higher inflammatory status for this patient group (Cohort 1; Table 1).

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