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

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 .

Efficacy of biologic therapies for biologic-naïve Japanese patients with moderately to severely active ulcerative colitis: a network meta-analysis

“…Four phase 3 RCTs were included in the NMA based on the eligibility criteria; publication dates ranged from 2014 to 2019. [16][17][18][19] Baseline study and patient characteristics are presented in Table 1. [16][17][18][19] Sample sizes per study ranged from 186 to 246 patients in 3 studies reporting efficacy outcomes in the induction phase [17][18][19] and from 63 to 273 patients in the maintenance phase in 4 studies.…”

“…[16][17][18][19] Baseline study and patient characteristics are presented in Table 1. [16][17][18][19] Sample sizes per study ranged from 186 to 246 patients in 3 studies reporting efficacy outcomes in the induction phase [17][18][19] and from 63 to 273 patients in the maintenance phase in 4 studies. [16][17][18][19] The mean age of patients ranged from 37.8 to 44.0 years across studies and treatment arms within individual studies.…”

Cost-Effectiveness Analysis of Vedolizumab Compared with Other Biologics in Anti-TNF-Naïve Patients with Moderate-to-Severe Ulcerative Colitis in Japan

“…IFX, ADA, and GOL were approved by the MHLW in 2010, 2013, and 2017, respectively, and VDZ and TOF in 2018 for the treatment of patients with moderate-to-severe UC who have not sufficiently responded to CT [14]. The efficacy and safety of VDZ for the treatment of patients with moderate-to-severe active UC have been demonstrated in an international study, GEMINI I, and a Japanese phase III VDZ study [15,16]. Previous studies have assessed the longterm clinical and economic consequences and cost-effectiveness of VDZ compared with other biologics for the treatment of patients with moderate-to-severe UC in the context of the United Kingdom (UK), Spain, and the United States (US) [17][18][19][20].…”

“…‡ Patients treated with a biologic can discontinue treatment at any time due to AEs and switch to CT. Patients treated with a biologic can also switch to induction CT if they lose their remission or response status during the maintenance phase a mean age of 42.8 years (range 16-77), as observed in the Japanese phase III VDZ study [16,22].…”

“…Clinical efficacy at the end of the maintenance phase was measured in terms of the percentage of patients who remain in remission or response-only (durable response) and in terms of the percentage of patients who remain in or achieve remission at the end of the maintenance phase. The cycle length of the maintenance phase was set to 1 year as the assessment of durable response and remission for the maintenance phase occurred approximately 1 year after the end of the induction phase in the Japanese phase III VDZ study [16].…”