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

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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.

Original languageEnglish
Article numbere0212989
JournalPloS one
Volume14
Issue number2
DOIs
Publication statusPublished - 2019 Feb 1

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colitis
Ulcerative Colitis
placebos
Placebos
remission
odds ratio
Maintenance
therapeutics
vedolizumab
endpoints
Odds Ratio
Safety
Japan
death
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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Vedolizumab in Japanese patients with ulcerative colitis : A Phase 3, randomized, double-blind, placebo-controlled study. / Motoya, Satoshi; Watanabe, Kenji; Ogata, Haruhiko; Kanai, Takanori; Matsui, Toshiyuki; Suzuki, Yasuo; Shikamura, Mitsuhiro; Sugiura, Kenkichi; Oda, Kazunori; Hori, Tetsuharu; Araki, Takahiro; Watanabe, Mamoru; Hibi, Toshifumi.

In: PloS one, Vol. 14, No. 2, e0212989, 01.02.2019.

Research output: Contribution to journalArticle

Motoya, S, Watanabe, K, Ogata, H, Kanai, T, Matsui, T, Suzuki, Y, Shikamura, M, Sugiura, K, Oda, K, Hori, T, Araki, T, Watanabe, M & Hibi, T 2019, 'Vedolizumab in Japanese patients with ulcerative colitis: A Phase 3, randomized, double-blind, placebo-controlled study', PloS one, vol. 14, no. 2, e0212989. https://doi.org/10.1371/journal.pone.0212989
Motoya, Satoshi ; Watanabe, Kenji ; Ogata, Haruhiko ; Kanai, Takanori ; Matsui, Toshiyuki ; Suzuki, Yasuo ; Shikamura, Mitsuhiro ; Sugiura, Kenkichi ; Oda, Kazunori ; Hori, Tetsuharu ; Araki, Takahiro ; Watanabe, Mamoru ; Hibi, Toshifumi. / Vedolizumab in Japanese patients with ulcerative colitis : A Phase 3, randomized, double-blind, placebo-controlled study. In: PloS one. 2019 ; Vol. 14, No. 2.
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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.",
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T2 - A Phase 3, randomized, double-blind, placebo-controlled study

AU - Motoya, Satoshi

AU - Watanabe, Kenji

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 - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

AB - 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.

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