Kiyosue Arihiro, Honarpour Narimon, Kurtz Christopher, Xue Allen, Wasserman Scott M, Hirayama Atsushi
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Tokyo-Eki Center-Building Clinic, Tokyo, Japan.
Amgen Inc., Thousand Oaks, California.
Am J Cardiol. 2016 Jan 1;117(1):40-7. doi: 10.1016/j.amjcard.2015.10.021. Epub 2015 Oct 19.
Evolocumab (AMG 145), a fully human monoclonal antibody against PCSK9, significantly reduced low-density lipoprotein cholesterol (LDL-C) levels in phase 2 and 3 studies. This phase 3 study evaluated the efficacy and safety of evolocumab plus atorvastatin in Japanese patients with hyperlipidemia or mixed dyslipidemia and high cardiovascular risk. Patients were randomized to atorvastatin 5 or 20 mg/day for 4 weeks. Subsequently, patients underwent second randomization to evolocumab 140 mg biweekly (Q2W) or 420 mg monthly (QM) or placebo Q2W or QM. Coprimary end points were % change from baseline in LDL-C at week 12 and mean of weeks 10 and 12. Secondary end points included change and % change in other lipids and proportion of patients reaching LDL-C <70 mg/dl. Adverse events and laboratory values were recorded. Four hundred four patients were randomized to study drug. At baseline, the mean (SD) age was 61 (10) years (placebo) and 62 (11) years (evolocumab); 39% and 40% were women; 14% and 12% had cerebrovascular or peripheral arterial disease; and 51% and 47% had diabetes. At entry, mean (SD) calculated LDL-C was 128 (23) mg/dL; after stabilization on atorvastatin 5 and 20 mg/day, baseline LDL-C levels were 118 (35) and 94 (24) mg/dL, respectively. Mean LDL-C reductions at week 12 for evolocumab versus placebo ranged from 67% to 76%. No imbalances were observed in adverse events between treatment groups. Efficacy and safety for Q2W or QM evolocumab dosing were similar. In conclusion, in high-risk Japanese patients receiving stable statin therapy, evolocumab markedly reduced LDL-C and was well tolerated.
依洛尤单抗（AMG 145）是一种完全人源化的抗前蛋白转化酶枯草溶菌素9（PCSK9）单克隆抗体，在2期和3期研究中显著降低了低密度脂蛋白胆固醇（LDL-C）水平。这项3期研究评估了依洛尤单抗联合阿托伐他汀在日本高脂血症或混合性血脂异常且心血管风险高的患者中的疗效和安全性。患者被随机分为接受5毫克或20毫克/天阿托伐他汀治疗4周。随后，患者进行二次随机分组，分别接受每两周一次（Q2W）140毫克依洛尤单抗、每月一次（QM）420毫克依洛尤单抗或Q2W或QM的安慰剂治疗。共同主要终点是第12周时LDL-C相对于基线的百分比变化以及第10周和第12周的平均值。次要终点包括其他血脂的变化和百分比变化以及LDL-C<70毫克/分升的患者比例。记录不良事件和实验室值。404名患者被随机分配接受研究药物治疗。基线时，安慰剂组的平均（标准差）年龄为61（10）岁，依洛尤单抗组为62（11）岁；女性分别占39%和40%；有脑血管或外周动脉疾病的分别占14%和12%；患有糖尿病的分别占51%和47%。入组时，计算得出的平均（标准差）LDL-C为128（23）毫克/分升；在5毫克和20毫克/天阿托伐他汀稳定治疗后，基线LDL-C水平分别为118（35）和94（24）毫克/分升。依洛尤单抗组与安慰剂组在第12周时LDL-C的平均降低幅度在67%至76%之间。各治疗组之间未观察到不良事件的失衡。Q2W或QM依洛尤单抗给药的疗效和安全性相似。总之，在接受稳定他汀治疗的高危日本患者中，依洛尤单抗显著降低了LDL-C，且耐受性良好。
