Department of Endocrinology, Hematology and Gerontology Chiba University Graduate School of Medicine Chiba Japan.
Department of Cardiovascular Medicine Kitasato University School of Medicine Sagamihara Japan.
J Am Heart Assoc. 2024 Nov 5;13(21):e035809. doi: 10.1161/JAHA.124.035809. Epub 2024 Oct 29.
Evolocumab is the first monoclonal antibody against proprotein convertase subtilisin/kexin type 9 approved in Japan for familial hypercholesterolemia (FH) and hypercholesterolemia; however, data on its safety and effectiveness in the real-world setting in Japan are limited.
This real-world, postmarketing, single-arm study assessed the safety and effectiveness of low-density lipoprotein cholesterol lowering with evolocumab in patients with homozygous/heterozygous familial hypercholesterolemia and hypercholesterolemia with high risk in Japan (668 sites). The primary safety end point was the incidence (percentage) and number of patients with adverse drug reactions and serious adverse events during the 104-week follow-up. Primary effectiveness end points included the percentage change in low-density lipoprotein cholesterol levels from baseline to week 12, assessed using 2-sided paired tests. The safety and effectiveness sets comprised 3724 (homozygous FH, n=108; heterozygous FH, n=2009; hypercholesterolemia with high risk, n=1607) and 2797 (homozygous FH, n=91; heterozygous FH, n=1615; hypercholesterolemia with high risk, n=1091) patients, respectively. Overall, mean age and disease duration were 63.2 and 12.3 years, respectively. Serious adverse drug reactions and serious adverse events were experienced by 0.5% and 10.3% of patients; the incidence rates of myocardial infarction and stroke were 0.7% and 0.3%, respectively. A significant mean±SD percentage change in low-density lipoprotein cholesterol levels was observed at week 12 among patients with homozygous FH (-45.7%±28.2; <0.001), heterozygous FH (-55.9%±28.8; <0.001), and hypercholesterolemia with high risk (-63.3%±23.7; <0.001).
Evolocumab was well tolerated, and real-world patients with familial hypercholesterolemia and hypercholesterolemia with high risk in Japan had sustained low-density lipoprotein cholesterol reduction.
URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02808403.
依洛尤单抗是日本批准用于家族性高胆固醇血症（FH）和高胆固醇血症的首个针对前蛋白转化酶枯草溶菌素/ 丝氨酸蛋白酶 9 的单克隆抗体；然而，在日本真实环境中关于其安全性和有效性的数据有限。
这项真实世界、上市后、单臂研究评估了依洛尤单抗在日本纯合子/杂合子家族性高胆固醇血症和高胆固醇血症高危患者中的降低低密度脂蛋白胆固醇的安全性和有效性（668 个地点）。主要安全性终点是在 104 周随访期间不良药物反应和严重不良事件的发生率（百分比）和患者人数。主要有效性终点包括使用双侧配对 t 检验从基线到第 12 周时低密度脂蛋白胆固醇水平的百分比变化。安全性和有效性集分别包括 3724 例（纯合子 FH，n=108；杂合子 FH，n=2009；高胆固醇血症高危，n=1607）和 2797 例（纯合子 FH，n=91；杂合子 FH，n=1615；高胆固醇血症高危，n=1091）患者。总体而言，平均年龄和疾病持续时间分别为 63.2 岁和 12.3 年。0.5%的患者出现严重药物不良反应，10.3%的患者出现严重不良事件；心肌梗死和中风的发生率分别为 0.7%和 0.3%。在纯合子 FH（-45.7%±28.2；<0.001）、杂合子 FH（-55.9%±28.8；<0.001）和高胆固醇血症高危（-63.3%±23.7；<0.001）患者中，第 12 周时低密度脂蛋白胆固醇水平的平均（±SD）百分比变化显著。
依洛尤单抗具有良好的耐受性，日本真实世界中患有家族性高胆固醇血症和高胆固醇血症高危的患者持续降低低密度脂蛋白胆固醇。
