IBD Center, Hokkaido Prefectural Welfare Federation of Agricultural Cooperative, Sapporo-Kosei General Hospital, Sapporo, Japan.
Department of Intestinal Inflammation Research, Hyogo College of Medicine, Hyogo, Japan.
PLoS One. 2019 Feb 26;14(2):e0212989. doi: 10.1371/journal.pone.0212989. eCollection 2019.
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).
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.
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.
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.
ClinicalTrials.gov: NCT02039505.
维得利珠单抗在世界许多人群中的安全性和疗效已得到证实，但从未在日本进行过研究。我们报告了一项维得利珠单抗治疗日本活动性溃疡性结肠炎（UC）患者的 3 期、随机、双盲、安慰剂对照研究的结果。
中重度 UC 患者在诱导期进入队列 1（双盲）或队列 2（开放标签）。队列 1 按 2:1 的比例随机接受 300mg 维得利珠单抗或安慰剂，而队列 2 仅在第 0、2 和 6 周接受维得利珠单抗 300mg。第 10 周对维得利珠单抗有临床反应的队列 1 和 2 的患者按 1:1 的比例随机接受维得利珠单抗或安慰剂（双盲），然后在第 14 周和第 54 周前每 8 周进行一次维持治疗。主要终点为诱导期第 10 周的临床反应和维持期第 60 周的临床缓解。
共有 292 名患者进入诱导期（队列 1 246 名，队列 2 46 名）；83 名患者对维得利珠单抗有反应，随后进入维持期。队列 1 中维得利珠单抗组第 10 周的临床反应率分别为 39.6%（65/164）和 32.9%（27/82）（调整后的优势比[AOR] = 1.37，95%置信区间[CI] 0.779-2.399；p = 0.2722）。在维持期，维得利珠单抗组第 60 周的临床缓解率显著高于安慰剂组，分别为 56.1%（23/41）和 31.0%（13/42）（AOR = 2.88，95%CI 1.168-7.108；p = 0.0210）。大多数不良事件的严重程度为轻度至中度，研究期间无死亡事件发生。
与安慰剂相比，维得利珠单抗作为诱导治疗的疗效有一定优势，但差异无统计学意义。在日本 UC 患者中，维得利珠单抗作为维持治疗明显优于安慰剂。维得利珠单抗在这些患者中具有良好的安全性和耐受性。
ClinicalTrials.gov：NCT02039505。
