Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis
Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis
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DOI：
10.1056/nejmoa1512711
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发表时间：
2016-07-28
影响因子：
158.5
通讯作者：
Leonardi, C. L.
中科院分区：
文献类型：
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作者：
Gordon, K. B.;Blauvelt, A.;Leonardi, C. L.
两项3期试验（UNCOVER-2和UNCOVER-3）显示，在治疗12周时，ixekizumab（一种抗白细胞介素-17A的单克隆抗体）在治疗中重度银屑病方面上级安慰剂和依那西普。我们报告了来自UNCOVER-2和UNCOVER-3试验的60周数据，以及来自第三个3期试验UNCOVER-1的12周和60周数据。方法我们随机分配了UNCOVER-1试验的1296例患者，UNCOVER-2试验的1224例患者和UNCOVER-3试验的1346例患者接受皮下注射安慰剂（安慰剂组）、160 mg起始剂量后每2周80 mg ixekizumab（2周给药组）或160 mg起始剂量后每4周80 mg ixekizumab（4周给药组）。UNCOVER-2和UNCOVER-3试验中的其他队列被随机分配接受50 mg依那西普每周两次。在UNCOVER-3试验的第12周，患者进入长期扩展期，在此期间，他们每4周一次接受80 mg ixekizumab，直至第60周;在UNCOVER-1和UNCOVER-2试验的第12周，对ixekizumab有反应的患者（定义为静态医师总体评估[sPGA]评分为0 [清除]或1 [轻微银屑病]）随机重新分配接受安慰剂、80 mg ixekizumab每4周一次，或80 mg ixekizumab，每12周一次，直至第60周。共同主要终点是在第12周sPGA评分为0或1，并且银屑病面积和严重程度指数（PASI 75）较基线降低75%或以上的患者百分比。在UNCOVER-1试验中，在第12周，患者对ixekizumab的反应优于安慰剂;在2周给药组中，81.8%的sPGA评分为0或1，89.1%的PASI 75应答;在4周给药组中，相应的比率为76.4%和82.6%;在安慰剂组中，比率为3.2%和3.9%（P
BACKGROUNDTwo phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1.METHODSWe randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12.RESULTSIn the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P