医学
高甘油三酯血症
内科学
队列
急性胰腺炎
安慰剂
胃肠病学
临床终点
脂蛋白脂酶
随机对照试验
胰腺炎
不利影响
内分泌学
甘油三酯
胆固醇
脂肪组织
病理
替代医学
作者
Robert S. Rosenson,Daniel Gaudet,Christie M. Ballantyne,Sharon Baum,Jean Bergeron,Erin E. Kershaw,Patrick M. Moriarty,P. Rubba,David C. Whitcomb,Poulabi Banerjee,Andrew Gewitz,Claudia Gonzaga‐Jauregui,Jennifer McGinniss,Manish P. Ponda,Robert Pordy,Jian Zhao,Daniel J. Rader
出处
期刊:Nature Medicine
[Springer Nature]
日期:2023-03-01
卷期号:29 (3): 729-737
被引量:27
标识
DOI:10.1038/s41591-023-02222-w
摘要
Abstract Severe hypertriglyceridemia (sHTG) is an established risk factor for acute pancreatitis. Current therapeutic approaches for sHTG are often insufficient to reduce triglycerides and prevent acute pancreatitis. This phase 2 trial ( NCT03452228 ) evaluated evinacumab (angiopoietin-like 3 inhibitor) in three cohorts of patients with sHTG: cohort 1, familial chylomicronemia syndrome with bi-allelic loss-of-function lipoprotein lipase (LPL) pathway mutations ( n = 17); cohort 2, multifactorial chylomicronemia syndrome with heterozygous loss-of-function LPL pathway mutations ( n = 15); and cohort 3, multifactorial chylomicronemia syndrome without LPL pathway mutations ( n = 19). Fifty-one patients (males, n = 27; females, n = 24) with a history of hospitalization for acute pancreatitis were randomized 2:1 to intravenous evinacumab 15 mg kg −1 or placebo every 4 weeks over a 12-week double-blind treatment period, followed by a 12-week single-blind treatment period. The primary end point was the mean percent reduction in triglycerides from baseline after 12 weeks of evinacumab exposure in cohort 3. Evinacumab reduced triglycerides in cohort 3 by a mean (s.e.m.) of −27.1% (37.4) (95% confidence interval −71.2 to 84.6), but the prespecified primary end point was not met. No notable differences in adverse events between evinacumab and placebo treatment groups were seen during the double-blind treatment period. Although the primary end point of a reduction in triglycerides did not meet the prespecified significance level, the observed safety and changes in lipid and lipoprotein levels support the further evaluation of evinacumab in larger trials of patients with sHTG. Trial registration number: ClinicalTrials.gov NCT03452228 .
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