The purpose of this study is to evaluate efficacy, safety and pharmacokinetics of the vedolizumab (MLN0002) induction and maintenance therapy in Japanese participants with moderate or severe ulcerative colitis (UC).
Background: Vedolizumab (VDZ), a monoclonal antibody that inhibits α4 β7 integrin, is approved in multiple Western countries for the treatment of ulcerative colitis (UC); however, data on its efficacy and safety are limited in Asian patients (pts). In addition, the efficacy of VDZ after 10-weeks induction has not been investigated. We performed a phase 3, multicentre, randomized, double-blind, placebo (PBO)-controlled, parallel-group study of VDZ in Japanese pts with UC (NCT02039505). Methods: Pts with moderately to severely active UC (with baseline complete Mayo score 6-12 and endoscopic subscore ≥2, who had failed existing pharmacotherapy) were enrolled into cohort 1 (C1, double-blinded) or cohort 2 (C2, open-label) in the induction phase (IP). Pts in C1 were randomized 2:1 to receive 300 mg of VDZ by intravenous infusion, or PBO, at Weeks 0, 2, 6. All pts in C2 received VDZ 300 mg at Weeks 0, 2, 6. Pts in C1 or C2 showing a clinical response to VDZ at Week 10 were enrolled into the maintenance phase (MP) at Week 14 and were randomized 1:1 to receive VDZ 300 mg or PBO (double-blinded), at Week 14 and every 8 weeks thereafter up to Week 54. The primary endpoints were clinical response rate at Week 10 for the IP (C1 only), and clinical remission rate at Week 60 for the MP. Results: A total of 292 pts were enrolled into the IP (246 pts in C1, 46 pts in C2). Baseline characteristics were comparable in all groups, except for extraintestinal manifestations, which were more frequent in the VDZ group (32.3%) compared with placebo (19.5%); 51.4% of pts had prior anti-TNFα therapy. Week 10 clinical response was achieved in 39.6% (65/164) of pts in the VDZ group and 32.9% (27/82) of pts in the PBO group; the between-group difference was not statistically significant (adjusted odds ratio [AOR]=1.37; 95% CI, 0.78-2.40; p=0.27). In the MP, clinical remission rate at Week 60 was statistically significantly superior for the VDZ group at 56.1% (23/41 pts) compared with 31.0% (13/42 pts) for the PBO group (AOR=2.88; 95% CI, 1.17-7.11; p=0.021). There were no clear differences between treatment groups in the incidence of treatment-emergent adverse events (TEAEs). Most of the TEAEs occurring in either study group, in either IP or MP, were mild to moderate in intensity. No cases of progressive multifocal leukoencephalopathy were reported and no deaths occurred during the study. Conclusions: In Japanese pts with UC, VDZ showed a numerically higher clinical response rate compared with placebo in the IP, but the difference was not statistically significant. As maintenance therapy, VDZ was significantly superior to placebo for clinical remission rate at Week 60. VDZ is safe and well-tolerated in induction and maintenance therapy for Japanese pts with UC.
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.
An incorrect version of S2 File was published in error. This article was republished on April 2, 2019 to correct for this error. Please download this article again to view the correct version.
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).
The purpose of this study is to evaluate efficacy, safety and pharmacokinetics of the vedolizumab (MLN0002) induction and maintenance therapy in Japanese participants with moderate or severe ulcerative colitis (UC).
