Department of Dermatology, Oregon Health and Science University, 2565 NW Lovejoy #200, Portland, OR, USA.
Br J Dermatol. 2013 Feb;168(2):402-11. doi: 10.1111/bjd.12112.
Interleukin (IL)-17A has major proinflammatory activity in psoriatic lesional skin.
To assess the efficacy and safety of secukinumab, a fully human IgG1κ monoclonal anti-IL-17A antibody, in moderate-to-severe plaque psoriasis in a phase II regimen-finding study.
A total of 404 patients were randomized to subcutaneous placebo (n = 67) or one of three secukinumab 150 mg induction regimens: single (week 0; n = 66), early (weeks 0, 1, 2, 4; n = 133) and monthly (weeks 0, 4, 8; n = 138 patients). The primary outcome was ≥ 75% improvement from baseline Psoriasis Area and Severity Index score (PASI 75) at week 12. PASI 75 responders from active treatment arms at week 12 were rerandomized to either a fixed-interval (secukinumab 150 mg at weeks 12 and 24; n = 65) or a treatment-at-start-of-relapse maintenance regimen (secukinumab 150 mg at visits at which a start of relapse was observed; n = 67).
At week 12, early and monthly induction regimens resulted in higher PASI 75 response rates vs. placebo (54·5% and 42·0% vs. 1·5%; P < 0·001 for both). Among PASI 75 responders at week 12 entering the maintenance period, PASI 75 and PASI 90 achievement at least once from week 20 to week 28 was superior with the fixed-interval regimen [85% (n = 55) and 58% (n = 38), respectively] vs. the start-of-relapse regimen [67% (n = 45), P = 0·020, and 21% (n = 14), respectively]. Fifteen weeks after last study drug administration, < 10% of patients in the fixed-interval and start-of-relapse groups experienced a start of relapse. No immunogenicity was observed, and no injection-site reactions were reported. Reported cases of neutropenia were mild-to-moderate (≤ grade 2); none was associated with clinically significant adverse events or resulted in study discontinuation. Due to the brief duration of the safety assessment, no firm conclusions can be drawn regarding long-term safety.
Secukinumab shows efficacy for induction and maintenance treatment of moderate-to-severe plaque psoriasis.
白细胞介素（IL）-17A 在银屑病皮损中具有主要的促炎活性。
评估 secukinumab（一种完全人源 IgG1κ 单克隆抗 IL-17A 抗体）在中度至重度斑块型银屑病中的疗效和安全性，这是一项 II 期方案发现研究。
共有 404 名患者被随机分配至皮下安慰剂（n = 67）或 secukinumab 150 mg 三种诱导方案中的一种：单次（第 0 周；n = 66）、早期（第 0、1、2、4 周；n = 133）和每月（第 0、4、8 周；n = 138 名患者）。主要终点是在第 12 周时从基线银屑病面积和严重程度指数评分（PASI 75）改善≥75%。在第 12 周时，接受活性治疗的手臂中达到 PASI 75 的患者被重新随机分配至固定间隔（第 12 周和第 24 周时给予 secukinumab 150 mg；n = 65）或治疗开始时复发的维持治疗方案（观察到复发开始时给予 secukinumab 150 mg；n = 67）。
在第 12 周时，早期和每月诱导方案与安慰剂相比，PASI 75 应答率更高（54.5%和 42.0% vs. 1.5%；两者均 < 0.001）。在第 12 周时达到 PASI 75 的患者中，有 15 周未接受研究药物治疗，固定间隔方案（分别为 85%（n = 55）和 58%（n = 38））和开始复发方案（分别为 67%（n = 45）和 21%（n = 14））从第 20 周到第 28 周至少有一次达到 PASI 75 和 PASI 90 的比例更高（P = 0.020）。在最后一次研究药物给药后 15 周，固定间隔组和开始复发组中 < 10%的患者出现复发。未观察到免疫原性，也未报告注射部位反应。报告的中性粒细胞减少症为轻度至中度（≤2 级）；均与临床相关不良事件无关，也未导致研究中止。由于安全性评估的持续时间较短，因此无法对长期安全性得出明确结论。
secukinumab 对中重度斑块型银屑病的诱导和维持治疗有效。
