Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis
Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis
复制标题
DOI：
10.1056/nejmoa1503824
复制
发表时间：
2015-10-01
影响因子：
158.5
通讯作者：
Nirula, A.
中科院分区：
文献类型：
--
作者：
Lebwohl, M.;Strober, B.;Nirula, A.
背景早期临床研究表明，抗白细胞介素 17 受体 A 单克隆抗体 brodalumab 对治疗银屑病具有疗效。 方法在两项 3 期研究（AMAGINE-2 和 AMAGINE-3）中，中重度银屑病患者被随机分配接受 brodalumab（每 2 周 210 mg 或 140 mg）、乌特克单抗（体重 100 公斤的患者 45 mg）。公斤），或安慰剂。第12周时，接受brodalumab的患者再次随机分配接受每2周210 mg的brodalumab维持剂量或每2周、每4周或每8周140 mg；接受优特克单抗治疗的患者继续每 12 周接受一次优特克单抗治疗，接受安慰剂的患者每两周接受 210 毫克 brodalumab 治疗。主要目的是评估第 12 周时 Brodalumab 相对于安慰剂的优越性，即银屑病面积和严重程度指数评分 (PASI 75) 降低至少 75%，静态医师整体评估 (sPGA) 评分为 0 或 1（皮肤透明或几乎透明），以及第 12 周时 Brodalumab 相对于乌特克单抗的优越性，PASI 评分降低 100% (PASI 100)。结果在第 12 周，210 mg 和 140 mg 剂量的 brodalumab 组的 PASI 75 缓解率高于安慰剂组（分别为 86% 和 67%， vs. 8% [AMAGINE-2]；分别为 85% 和 69%， vs. 6% [AMAGINE-3]；P
BACKGROUNDEarly clinical studies suggested that the anti-interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis.METHODSIn two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight 100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of brodalumab every 2 weeks. The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physician's global assessment (sPGA) score of 0 or 1 (clear or almost clear skin), as well as the superiority of brodalumab over ustekinumab at week 12 with respect to a 100% reduction in PASI score (PASI 100).RESULTSAt week 12, the PASI 75 response rates were higher with brodalumab at the 210-mg and 140-mg doses than with placebo (86% and 67%, respectively, vs. 8% [AMAGINE-2] and 85% and 69%, respectively, vs. 6% [AMAGINE-3]; P