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

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

Research output: Contribution to journalArticle

Abstract

Background: Vedolizumab is a gut-selective humanized antibody that binds the α4β7 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.

Original languageEnglish
JournalJournal of gastroenterology
DOIs
Publication statusAccepted/In press - 2019 Jan 1

Fingerprint

Crohn Disease
Placebos
Maintenance
Odds Ratio
Confidence Intervals
Antibodies, Monoclonal, Humanized
vedolizumab
Remission Induction
Double-Blind Method
Integrins
Therapeutics
Safety
Incidence

Keywords

  • Biologic
  • Crohn’s disease
  • Randomized controlled trial
  • Vedolizumab
  • αβ integrin

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Effects of vedolizumab in Japanese patients with Crohn’s disease : a prospective, multicenter, randomized, placebo-controlled Phase 3 trial with exploratory analyses. / Watanabe, Kenji; Motoya, Satoshi; Ogata, Haruhiko; Kanai, Takanori; Matsui, Toshiyuki; Suzuki, Yasuo; Shikamura, Mitsuhiro; Sugiura, Kenkichi; Oda, Kazunori; Hori, Tetsuharu; Araki, Takahiro; Watanabe, Mamoru; Hibi, Toshifumi.

In: Journal of gastroenterology, 01.01.2019.

Research output: Contribution to journalArticle

Watanabe, Kenji ; Motoya, Satoshi ; Ogata, Haruhiko ; Kanai, Takanori ; Matsui, Toshiyuki ; Suzuki, Yasuo ; Shikamura, Mitsuhiro ; Sugiura, Kenkichi ; Oda, Kazunori ; Hori, Tetsuharu ; Araki, Takahiro ; Watanabe, Mamoru ; Hibi, Toshifumi. / Effects of vedolizumab in Japanese patients with Crohn’s disease : a prospective, multicenter, randomized, placebo-controlled Phase 3 trial with exploratory analyses. In: Journal of gastroenterology. 2019.
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abstract = "Background: Vedolizumab is a gut-selective humanized antibody that binds the α4β7 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.",
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T2 - a prospective, multicenter, randomized, placebo-controlled Phase 3 trial with exploratory analyses

AU - Watanabe, Kenji

AU - Motoya, Satoshi

AU - Ogata, Haruhiko

AU - Kanai, Takanori

AU - Matsui, Toshiyuki

AU - Suzuki, Yasuo

AU - Shikamura, Mitsuhiro

AU - Sugiura, Kenkichi

AU - Oda, Kazunori

AU - Hori, Tetsuharu

AU - Araki, Takahiro

AU - Watanabe, Mamoru

AU - Hibi, Toshifumi

PY - 2019/1/1

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N2 - Background: Vedolizumab is a gut-selective humanized antibody that binds the α4β7 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.

AB - Background: Vedolizumab is a gut-selective humanized antibody that binds the α4β7 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.

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KW - Crohn’s disease

KW - Randomized controlled trial

KW - Vedolizumab

KW - αβ integrin

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