Efficacy and safety of ixekizumab for the treatment of moderate-to-severe plaque psoriasis: Results through 108 weeks of a randomized, controlled phase 3 clinical trial (UNCOVER-3)
Efficacy and safety of ixekizumab for the treatment of moderate-to-severe plaque psoriasis: Results through 108 weeks of a randomized, controlled phase 3 clinical trial (UNCOVER-3)
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DOI：
10.1016/j.jaad.2017.06.153
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发表时间：
2017-11-01
影响因子：
13.8
通讯作者：
Reich, Kristian
中科院分区：
文献类型：
--
作者：
Blauvelt, Andrew;Gooderham, Melinda;Reich, Kristian
背景资料：Ixekizumab是一种选择性靶向白细胞介素17 A的高亲和力单克隆抗体，可有效治疗中重度斑块型银屑病60 wk，目的：在UNCOVER-3中评价ixekizumab治疗108 wk的疗效和安全性。方法：患者（N = 1346）按2：2：2：1的比例随机分为80 mg ixekizumab每2或4 wk、50 mg依那西普每周2次或安慰剂组。在第12周，患者在长期扩展（LTE）期间每4周一次转换为ixekizumab。使用观察值、多重插补（MI）和改良MI（mMI）方法总结疗效数据。对于接受推荐剂量的患者（N = 385）（第0-12周ixekizumab每2周一次，LTE期间每4周一次），108周观察缓解率、MI缓解率和mMI缓解率分别为93.4%、88.3%和83.6%，对于Psb面积和严重程度指数较基线改善≥ 75%的患者，静态医师总体评估评分为0或1的患者，108周观察时MI和mMI缓解率分别为82.6%、78.3%和74.1%。在LTE期间，1077例（84.5%）患者报告了≥ 1例治疗后出现的不良事件，85%的严重程度为轻度或中度。6.4%的患者因不良事件而停药。局限性：12周后无对照治疗组。结论：Ixekizumab耐受性良好，疗效持续至108周。
Background: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin 17A, is efficacious in treating moderate-to-severe plaque psoriasis through 60 weeks.Objective: To evaluate the efficacy and safety of ixekizumab through 108 weeks of treatment in UNCOVER-3.Methods: Patients (N = 1346) were randomized 2:2:2:1 to 80 mg ixekizumab every 2 or 4 weeks, 50 mg etanercept twice weekly, or placebo. At week 12, patients switched to ixekizumab every 4 weeks during a long-term extension (LTE) period. Efficacy data were summarized using as-observed, multiple imputation (MI), and modified MI (mMI) methods.Results: For patients (N = 385) receiving the recommended dose (ixekizumab every 2 weeks on weeks 0-12 and every 4 weeks during LTE), the 108-week as-observed, MI, and mMI response rates were 93.4%, 88.3%, and 83.6%, respectively, for patients achieving >= 75% improvement from baseline in the Psoriasis Area and Severity Index, and the 108-week as-observed, MI, and mMI response rates were 82.6%, 78.3%, and 74.1%, respectively, for patients with a static Physician's Global Assessment score of 0 or 1. During LTE, 1077 (84.5%) patients reported >= 1 treatment-emergent adverse event, and 85% were mild or moderate in severity. Discontinuation because of adverse events occurred in 6.4% of patients.Limitations: There was no comparison treatment group after week 12.Conclusion: Ixekizumab is well tolerated and demonstrates persistent efficacy through 108 weeks.