Abstract

Introduction

Homozygous Familial Hypercholesterolemia (HoFH) is a very severe genetic form of hypercholesterolemia. Lacking LDL receptors in the liver, subjects with HoFH have raised plasma levels of LDL cholesterol, and up to 100 times higher risk of premature atherosclerotic cardiovascular disease than the general population.

Areas covered

This evaluation is of a phase 3 trial of evinacumab; Evinacumab Lipid Studies in Patients with Homozygous Familial Hypercholesterolemia (ELIPSE HoFH). Evinacumab is a human monoclonal antibody inhibitor of angiopoietin-like protein 3 (ANGPTL3). In ELIPSE HoFH, evinacumab reduced LDL cholesterol by 47.1 ± 4.6%, HDL cholesterol by 30.4%, and triglycerides by 50.4 ± 7.7%.

Expert opinion

Evinacumab is not the ideal treatment for HoFH as it does not reduce LDL cholesterol levels to treatment targets, while increasing HDL cholesterol. Although the incidence of adverse effects with evinacumab were low in ELIPSE HoFH, further studies are necessary to clarify its effects on liver enzymes and clinical cardiovascular outcomes. Evinacumab is a candidate to become the standard treatment for HoFH, as it may be better tolerated and/or more efficacious than the presently available specific treatment (lomitapide). However, the widespread use of evinacumab to treat high triglycerides or LDL cholesterol is unlikely due to evinacumab decreasing HDL cholesterol.

中文翻译：

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evinacumab会成为纯合子家族性高胆固醇血症的标准治疗方法吗？

摘要

介绍

纯合子家族性高胆固醇血症（HoFH）是高胆固醇血症的一种非常严重的遗传形式。肝中缺乏LDL受体的HoFH患者血浆LDL胆固醇水平升高，过早动脉粥样硬化性心血管疾病的风险比普通人群高100倍。

覆盖区域

该评价是依那那单抗的3期试验；纯合子家族性高胆固醇血症（ELIPSE HoFH）患者的依那考单抗脂质研究。Evinacumab是血管生成素样蛋白3（ANGPTL3）的人类单克隆抗体抑制剂。在ELIPSE HoFH中，evinacumab使LDL胆固醇降低47.1±4.6％，HDL胆固醇降低30.4％，甘油三酸酯降低50.4±7.7％。

专家意见

Evinacumab不是HoFH的理想治疗方法，因为它不会将LDL胆固醇水平降低至治疗目标，而会增加HDL胆固醇。尽管在ELIPSE HoFH中使用evinacumab的不良反应发生率较低，但仍需要进一步的研究来阐明其对肝酶和临床心血管结局的影响。Evinacumab是可能成为HoFH标准治疗药物的候选药物，因为与目前可用的特异性治疗药物（洛米他肽）相比，它可以更好地耐受和/或更有效。但是，由于依维那古那降低了HDL胆固醇，因此不太可能广泛使用依维那古那治疗高甘油三酸酯或LDL胆固醇。