Center for Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Probity Medical Research and K Papp Clinical Research, Waterloo, ON, Canada.
Lancet. 2021 Feb 6;397(10273):487-498. doi: 10.1016/S0140-6736(21)00125-2.
There is an unmet need for a treatment for psoriasis that results in complete skin clearance with a reliably quick response. Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. We aimed to compare the efficacy and safety of bimekizumab with placebo and ustekinumab in patients with moderate to severe plaque psoriasis over 52 weeks.
BE VIVID was a multicentre, randomised, double-blind, active comparator and placebo controlled phase 3 trial done across 105 sites (clinics, hospitals, research units, and private practices) in 11 countries in Asia, Australia, Europe, and North America. Adults aged 18 years or older with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] score ≥12, ≥10% body surface area affected by psoriasis, and Investigator's Global Assessment [IGA] score ≥3 on a five point scale) were included. Randomisation was stratified by geographical region and previous exposure to biologics; patients, investigators, and sponsors were masked to treatment assignment. Patients were randomly assigned (4:2:1) using an interactive response technology to bimekizumab 320 mg every 4 weeks, ustekinumab 45 mg or 90 mg (baseline weight-dependent dosing) at weeks 0 and 4, then every 12 weeks, or placebo every 4 weeks. At week 16, patients receiving placebo switched to bimekizumab 320 mg every 4 weeks. All study treatments were administered as two subcutaneous injections. Coprimary endpoints were the proportion of patients with 90% improvement in the PASI (PASI90) and the proportion of patients with an IGA response of clear or almost clear (score 0 or 1) at week 16 (non-responder imputation). Efficacy analyses included the intention-to-treat population; safety analysis included patients who received at least one dose of study treatment. This trial was registered at ClinicalTrials.gov, NCT03370133 (completed).
Between Dec 6, 2017, and Dec 13, 2019, 735 patients were screened and 567 were enrolled and randomly assigned (bimekizumab 320 mg every 4 weeks n=321, ustekinumab 45 mg or 90 mg every 12 weeks n=163, placebo n=83). At week 16, 273 (85%) of 321 patients in the bimekizumab group had PASI90 versus 81 (50%) of 163 in the ustekinumab group (risk difference 35 [95% CI 27-43]; p<0·0001) and four (5%) of 83 in the placebo group (risk difference 80 [74-86]; p<0·0001). At week 16, 270 (84%) patients in the bimekizumab group had an IGA response versus 87 (53%) in the ustekinumab group (risk difference 30 [95% CI 22-39]; p<0·0001) and four (5%) in the placebo group (risk difference 79 [73-85]; p<0·0001). Over 52 weeks, serious treatment-emergent adverse events were reported in 24 (6%) of 395 patients in the bimekizumab group (including those who switched from placebo at week 16) and 13 (8%) of 163 in the ustekinumab group.
Bimekizumab was more efficacious than ustekinumab and placebo in the treatment of moderate to severe plaque psoriasis. The bimekizumab safety profile was consistent with that observed in previous studies.
UCB Pharma.
目前，人们对于能够实现皮肤完全清除且具有可靠快速应答的银屑病治疗方法存在未满足的需求。Bimekizumab 是一种单克隆 IgG1 抗体，除了抑制白细胞介素（IL）-17A 外，还选择性地抑制 IL-17F。我们旨在比较 bimekizumab 与安慰剂和乌司奴单抗在中重度斑块状银屑病患者中的疗效和安全性，为期 52 周。
BE VIVID 是一项多中心、随机、双盲、活性对照和安慰剂对照的 3 期临床试验，在 11 个国家（亚洲、澳大利亚、欧洲和北美）的 105 个地点（诊所、医院、研究单位和私人诊所）进行。纳入年龄在 18 岁及以上、中重度斑块状银屑病（PASI 评分≥12、≥10%体表面积受银屑病影响和研究者全球评估 [IGA] 评分为 5 分制的 3 分）的成年人。患者按地理位置和以前是否接触过生物制剂进行分层随机分组；患者、研究者和赞助商对治疗分配进行了盲法。患者使用交互式反应技术随机分配（4:2:1）接受每 4 周一次的 bimekizumab 320mg、乌司奴单抗 45mg 或 90mg（根据基线体重依赖性剂量），然后每 12 周一次，或每 4 周一次安慰剂。在第 16 周，接受安慰剂的患者转换为每 4 周一次的 bimekizumab 320mg。所有研究治疗均作为两次皮下注射给药。主要终点是 PASI90 改善比例（PASI90）和 IGA 应答为清除或几乎清除（评分 0 或 1）的患者比例（第 16 周非应答者推断）。疗效分析包括意向治疗人群；安全性分析包括至少接受一次研究治疗的患者。该试验在 ClinicalTrials.gov 注册，NCT03370133（已完成）。
在 2017 年 12 月 6 日至 2019 年 12 月 13 日期间，共有 735 名患者接受了筛选，567 名患者入组并随机分配（bimekizumab 320mg 每 4 周组 n=321，乌司奴单抗 45mg 或 90mg 每 12 周组 n=163，安慰剂组 n=83）。在第 16 周，bimekizumab 组 321 名患者中有 273 名（85%）达到 PASI90，乌司奴单抗组 163 名患者中有 81 名（50%）（风险差异 35[95%CI 27-43]；p<0·0001），安慰剂组 83 名患者中有 4 名（5%）（风险差异 80[74-86]；p<0·0001）。在第 16 周，bimekizumab 组 270 名患者（84%）有 IGA 应答，乌司奴单抗组 163 名患者中有 87 名（53%）（风险差异 30[95%CI 22-39]；p<0·0001），安慰剂组 83 名患者中有 4 名（5%）（风险差异 79[73-85]；p<0·0001）。在 52 周内，bimekizumab 组 395 名患者中有 24 名（6%）报告了严重的治疗突发不良事件（包括第 16 周从安慰剂转换的患者），乌司奴单抗组 163 名患者中有 13 名（8%）。
与乌司奴单抗和安慰剂相比，bimekizumab 在中重度斑块状银屑病的治疗中更有效。bimekizumab 的安全性与先前研究观察到的一致。
UCB Pharma。
