Hirayama Atsushi, Yamashita Shizuya, Inomata Hyoe, Kassahun Helina, Cyrille Marcoli, Ruzza Andrea, Yoshida Masayuki, Kiyosue Arihiro, Ma Yuhui, Teramoto Tamio
Division of Cardiology, Department of Medicine, Nihon University School of Medicine.
Departments of Community Medicine and Cardiovascular Medicine, Osaka University Graduate School of Medicine.
Circ J. 2017 Jun 23;81(7):1029-1035. doi: 10.1253/circj.CJ-16-1016. Epub 2017 Mar 29.
Evolocumab, a fully human monoclonal antibody against PCSK9, significantly reduced low-density lipoprotein-cholesterol (LDL-C) levels in Japanese patients by up to 76% when administered with a statin. We evaluated the efficacy and safety of 1 year of evolocumab in a pooled analysis of patients from the 12-week YUKAWA studies who continued into the open-label extension (OLE) OSLER studies.
YUKAWA-1 and YUKAWA-2 were conducted in hypercholesterolemic, high-cardiovascular-risk Japanese patients who were receiving statin therapy. Patients completing these studies were eligible for an OLE study. At OLE entry, patients were re-randomized 2:1 to evolocumab+standard of care (SOC) or SOC alone (OSLER-1: evolocumab 420 mg monthly; OSLER-2: evolocumab 140 mg biweekly or 420 mg monthly). A 1-year analysis was performed on patients enrolled from the YUKAWA studies into OSLER. At parent-study baseline (YUKAWA-1 or YUKAWA-2 patients continuing into OSLER), mean (SD) age was 61 (10) years; 39% were female; mean (SD) baseline LDL-C (on statin) was 119.7 (33.0) mg/dL. Overall rates of adverse events were comparable between evolocumab+SOC and SOC alone. In YUKAWA patients receiving evolocumab+SOC, mean (SE) reductions in LDL-C from parent-study baseline to OLE 1 year were 69.1% (1.2%; OSLER-1) and 65.1% (2.2%; OSLER-2).
In a pooled 1-year analysis of Japanese patients in the ongoing OSLER studies, treatment with evolocumab+SOC was well tolerated and resulted in sustained LDL-C reductions at 1 year.
依洛尤单抗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，与他汀类药物联合使用时，可使日本患者的低密度脂蛋白胆固醇（LDL-C）水平显著降低高达76%。我们在一项汇总分析中评估了依洛尤单抗治疗1年的疗效和安全性，该分析纳入了来自为期12周的汤川研究且继续进入开放标签扩展（OLE）OSLER研究的患者。
汤川-1和汤川-2研究针对接受他汀类药物治疗的高胆固醇血症、心血管高风险日本患者开展。完成这些研究的患者有资格参加OLE研究。在进入OLE研究时，患者按2:1重新随机分组，分别接受依洛尤单抗+标准治疗（SOC）或单独接受SOC（OSLER-1：依洛尤单抗每月420 mg；OSLER-2：依洛尤单抗每两周140 mg或每月420 mg）。对从汤川研究纳入OSLER研究的患者进行了为期1年的分析。在母研究基线时（继续进入OSLER研究的汤川-1或汤川-2患者），平均（标准差）年龄为61（10）岁；39%为女性；平均（标准差）基线LDL-C（服用他汀类药物时）为119.7（33.0）mg/dL。依洛尤单抗+SOC组与单独SOC组的总体不良事件发生率相当。在接受依洛尤单抗+SOC治疗的汤川研究患者中，从母研究基线到OLE研究1年时，LDL-C的平均（标准误）降幅分别为69.1%（1.2%；OSLER-1）和65.1%（2.2%；OSLER-2）。
在正在进行的OSLER研究中对日本患者进行的为期1年的汇总分析中发现，依洛尤单抗+SOC治疗耐受性良好，且在第1年可使LDL-C持续降低。
