Probity Medical Research, Waterloo, ON, Canada.
N Engl J Med. 2012 Mar 29;366(13):1181-9. doi: 10.1056/NEJMoa1109017.
In this phase 2, randomized, double-blind, placebo-controlled, dose-ranging study, we assessed the efficacy and safety of brodalumab (AMG 827), a human anti-interleukin-17-receptor monoclonal antibody, for the treatment of moderate-to-severe plaque psoriasis.
We randomly assigned patients with a score of 12 or higher on the psoriasis area-and-severity index (PASI, on which scores range from 0 to 72, with higher scores indicating more severe disease) and with 10% or more of their body-surface area affected by psoriasis to receive brodalumab (70 mg, 140 mg, or 210 mg at day 1 and weeks 1, 2, 4, 6, 8, and 10 or 280 mg monthly) or placebo. The primary end point was the percentage improvement from baseline in the PASI score at week 12. Secondary end points included improvement of at least 75% and at least 90% in the PASI score and the score on the static physician's global assessment at week 12.
A total of 198 patients underwent randomization. At week 12, the mean percentage improvements in the PASI score were 45.0% among patients receiving 70 mg of brodalumab, 85.9% among those receiving 140 mg, 86.3% among those receiving 210 mg, 76.0% among those receiving 280 mg, and 16.0% among those receiving placebo (P<0.001 for all comparisons with placebo). An improvement of at least 75% and at least 90% in the PASI score at week 12 was seen in 77% and 72%, respectively, of the patients in the 140-mg brodalumab group and in 82% and 75%, respectively, of the patients in the 210-mg group, as compared with 0% in the placebo group (P<0.001 for all comparisons). The percentage of patients with a static physician's global assessment of clear or minimal disease was 26%, 85%, 80%, and 69% with the 70-mg, 140-mg, 210-mg, and 280-mg doses, respectively, of brodalumab, as compared with 3% with placebo (P<0.01 for all comparisons with placebo). Two cases of grade 3 neutropenia were reported in the 210-mg brodalumab group. The most commonly reported adverse events in the combined brodalumab groups were nasopharyngitis (8%), upper respiratory tract infection (8%), and injection-site erythema (6%).
Brodalumab significantly improved plaque psoriasis in this 12-week, phase 2 study. (Funded by Amgen; ClinicalTrials.gov number, NCT00975637.).
在这项 2 期、随机、双盲、安慰剂对照、剂量范围研究中，我们评估了 brodalumab（AMG 827），一种人源抗白细胞介素-17 受体单克隆抗体，治疗中度至重度斑块型银屑病的疗效和安全性。
我们将 PASI（评分范围为 0 至 72，分数越高表示疾病越严重）得分为 12 或更高且身体 10%以上受银屑病影响的患者随机分配接受 brodalumab（70mg、140mg 或 210mg 于第 1 天和第 1、2、4、6、8、10 周以及第 1、2、4、6、8、10 周和第 10 周或每月 280mg）或安慰剂。主要终点是第 12 周 PASI 评分自基线的百分比改善。次要终点包括第 12 周 PASI 评分至少改善 75%和至少 90%以及静态医师整体评估评分改善。
共 198 名患者接受了随机分组。第 12 周时，接受 70mg brodalumab 的患者 PASI 评分的平均百分比改善为 45.0%，接受 140mg 的患者为 85.9%，接受 210mg 的患者为 86.3%，接受 280mg 的患者为 76.0%，接受安慰剂的患者为 16.0%（与安慰剂相比，所有比较均<0.001）。第 12 周时 PASI 评分至少改善 75%和至少 90%的患者分别为 77%和 72%，接受 140mg brodalumab 的患者为 82%和 75%，接受 210mg 的患者为 72%和 72%，接受安慰剂的患者为 0%（与安慰剂相比，所有比较均<0.001）。接受 70mg、140mg、210mg 和 280mg brodalumab 的患者中，分别有 26%、85%、80%和 69%的患者有静态医师整体评估为“清除或轻微疾病”，而接受安慰剂的患者为 3%（与安慰剂相比，所有比较均<0.01）。在 210mg brodalumab 组报告了 2 例 3 级中性粒细胞减少症。联合 brodalumab 组中最常见的不良事件是鼻咽炎（8%）、上呼吸道感染（8%）和注射部位红斑（6%）。
在这项为期 12 周的 2 期研究中，brodalumab 显著改善了斑块型银屑病。（由 Amgen 资助；ClinicalTrials.gov 编号，NCT00975637）。
