Secukinumab in Plaque Psoriasis - Results of Two Phase 3 Trials
Secukinumab in Plaque Psoriasis - Results of Two Phase 3 Trials
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DOI：
10.1056/nejmoa1314258
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发表时间：
2014-07-24
影响因子：
158.5
通讯作者：
Papavassilis, Charis
中科院分区：
文献类型：
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作者：
Langley, Richard G.;Elewski, Boni E.;Papavassilis, Charis
背景白细胞介素-17 A被认为是银屑病发病机制的核心。我们评估了Rakkinumab，一种全人抗白细胞介素-17A单克隆抗体，在中度至重度斑块状银屑病患者中的应用。（两种固定苏金单抗方案治疗银屑病的疗效和安全性）和固定装置（使用两种给药方案对苏金单抗与依那西普进行全年研究性检查，以确定在银屑病中的疗效），我们随机分配了738名患者，（在ERASURE研究中）和1306例患者（在FIXTURE研究中）皮下注射300 mg或150 mg剂量的阿基诺单抗（每周一次给药，持续5周，然后每4周一次），安慰剂，或（仅在FIXTURE研究中）依那西普50 mg（每周给药两次，持续12周，然后每周给药一次）。每项研究的目的是显示第12周时，在银屑病面积和严重程度指数评分（PASI 75）较基线降低75%或以上且评分为0（清除）或1的患者比例方面，克林尤单抗优于安慰剂（几乎清晰）基于5分改良研究者总体评估在第12周时符合PASI 75标准的患者比例在每个阿基诺单抗剂量下高于安慰剂或依那西普：在ERASURE研究中，300 mg阿基诺单抗组的发生率为81.6%，150 mg阿基诺单抗组为71.6%，安慰剂组为4.5%;在FIXTURE研究中，300 mg阿基诺单抗组的发生率为77.1%，150 mg阿基诺单抗组为67.0%，依那西普组为44.0%，安慰剂组为4.9%（P
BACKGROUNDInterleukin-17A is considered to be central to the pathogenesis of psoriasis. We evaluated secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis.METHODSIn two phase 3, double-blind, 52-week trials, ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis), we randomly assigned 738 patients (in the ERASURE study) and 1306 patients (in the FIXTURE study) to subcutaneous secukinumab at a dose of 300 mg or 150 mg (administered once weekly for 5 weeks, then every 4 weeks), placebo, or (in the FIXTURE study only) etanercept at a dose of 50 mg (administered twice weekly for 12 weeks, then once weekly). The objective of each study was to show the superiority of secukinumab over placebo at week 12 with respect to the proportion of patients who had a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) and a score of 0 (clear) or 1 (almost clear) on a 5-point modified investigator's global assessment (coprimary end points).RESULTSThe proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 81.6% with 300 mg of secukinumab, 71.6% with 150 mg of secukinumab, and 4.5% with placebo; in the FIXTURE study, the rates were 77.1% with 300 mg of secukinumab, 67.0% with 150 mg of secukinumab, 44.0% with etanercept, and 4.9% with placebo (P