当前位置:科学网首页 > 小柯机器人 >详情
Evolocumab可有效治疗杂合型家族性高胆固醇血症患儿
作者:小柯机器人 发布时间:2020/9/3 14:04:24

加拿大蒙特利尔大学Daniel Gaudet联合巴西圣保罗大学Raul D. Santos团队研究了Evolocumab治疗杂合型家族性高胆固醇血症患儿的疗效。2020年8月29日,该研究发表在《新英格兰医学杂志》上。

Evolocumab是针对前蛋白转化酶枯草杆菌蛋白酶Kexin-9的全人源单克隆抗体,广泛用于成年患者以降低低密度脂蛋白(LDL)胆固醇的水平。但其治疗杂合型家族性高胆固醇血症患儿的疗效尚不清楚。

研究组进行了一项为期24周、随机、双盲、安慰剂对照的试验,招募了157例10-17岁的杂合型家族性高胆固醇血症患儿,在入组前已接受稳定降脂治疗至少4周,其LDL胆固醇水平在130 mg/dL及以上,甘油三酯水平在400 mg/dL及以下。将其按2:1随机分组,其中104例接受Evolocumab治疗,53例接受安慰剂治疗。主要终点为从基线到第24周LDL胆固醇水平的变化百分比。

第24周时,Evolocumab组的LDL胆固醇水平与基线相比平均降低了44.5%,安慰剂组则平均降低了6.2%,差异显著。Evolocumab组的LDL胆固醇水平绝对降低了77.5 mg/dL,安慰剂组则降低了9.0 mg/dL,相差68.6 mg/dL。Evolocumab组中所有次要血脂变量结果均明显优于安慰剂组。在治疗期间,两组间的不良事件发生率没有显著差异。

总之,Evolocumab治疗家族性高胆固醇血症患儿可有效降低LDL胆固醇水平和其他血脂变量。

附:英文原文

Title: Evolocumab in Pediatric Heterozygous Familial Hypercholesterolemia | NEJM

Author: Raul D. Santos, M.D., Ph.D.,, Andrea Ruzza, M.D., Ph.D.,, G. Kees Hovingh, M.D., Ph.D.,, Albert Wiegman, M.D., Ph.D.,, Franois Mach, M.D.,, Christopher E. Kurtz, M.D.,, Andrew Hamer, M.D.,, Ian Bridges, M.Sc.,, Andrea Bartuli, M.D.,, Jean Bergeron, M.D.,, Tamás Szamosi, M.D.,, Saikat Santra, M.B., B.Chir.,, Claudia Stefanutti, M.D., Ph.D.,, Olivier S. Descamps, M.D., Ph.D.,, Susanne Greber-Platzer, M.D.,, Ilse Luirink, M.D., Ph.D.,, John J.P. Kastelein, M.D., Ph.D.,, and Daniel Gaudet, M.D., Ph.D.

Issue&Volume: 2020-08-29

Abstract: Abstract

Background

Evolocumab, a fully human monoclonal antibody directed against proprotein convertase subtilisin–kexin type 9, is widely used in adult patients to lower low-density lipoprotein (LDL) cholesterol levels. Its effects in pediatric patients with heterozygous familial hypercholesterolemia are not known.

Methods

We conducted a 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia. Patients 10 to 17 years of age who had received stable lipid-lowering treatment for at least 4 weeks before screening and who had an LDL cholesterol level of 130 mg per deciliter (3.4 mmol per liter) or more and a triglyceride level of 400 mg per deciliter (4.5 mmol per liter) or less were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab (420 mg) or placebo. The primary end point was the percent change in LDL cholesterol level from baseline to week 24; key secondary end points were the mean percent change in LDL cholesterol level from baseline to weeks 22 and 24 and the absolute change in LDL cholesterol level from baseline to week 24.

Results

A total of 157 patients underwent randomization and received evolocumab (104 patients) or placebo (53 patients). At week 24, the mean percent change from baseline in LDL cholesterol level was 44.5% in the evolocumab group and 6.2% in the placebo group, for a difference of 38.3 percentage points (P<0.001). The absolute change in the LDL cholesterol level was 77.5 mg per deciliter (2.0 mmol per liter) in the evolocumab group and 9.0 mg per deciliter (0.2 mmol per liter) in the placebo group, for a difference of 68.6 mg per deciliter (1.8 mmol per liter) (P<0.001). Results for all secondary lipid variables were significantly better with evolocumab than with placebo. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab and placebo groups.

Conclusions

In this trial involving pediatric patients with familial hypercholesterolemia, evolocumab reduced the LDL cholesterol level and other lipid variables.

DOI: 10.1056/NEJMoa2019910

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2019910

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home