Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome

作者：Erik S G Stroes, Veronica Alexander, Ewa Karwatowska‐Prokopczuk, Robert A. Hegele, Marcello Arca, Christie M. Ballantyne, Handrean Soran, Thomas A Prohaska, Shuting Xia, Henry N. Ginsberg, Joseph L. Witztum, Sotirios Tsimikas · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2400201 · 被引用次数：256 · 研究领域：Lipid metabolism and disorders、Diabetes, Cardiovascular Risks, and Lipoproteins、Peroxisome Proliferator-Activated Receptors

BACKGROUND: Familial chylomicronemia syndrome is a genetic disorder associated with severe hypertriglyceridemia and severe acute pancreatitis. Olezarsen reduces the plasma triglyceride level by reducing hepatic synthesis of apolipoprotein C-III. METHODS: In a phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with genetically identified familial chylomicronemia syndrome to receive olezarsen at a dose of 80 mg or 50 mg or placebo subcutaneously every 4 weeks for 49 weeks. There were two primary end points: the difference between the 80-mg olezarsen group and the placebo group in the percent change in the fasting triglyceride level from baseline to 6 months, and (to be assessed if the first was significant) the difference between the 50-mg olezarsen group and the placebo group. Secondary end points included the mean percent change from baseline in the apolipoprotein C-III level and an independently adjudicated episode of acute pancreatitis. RESULTS: A total of 66 patients underwent randomization; 22 were assigned to the 80-mg olezarsen group, 21 to the 50-mg olezarsen group, and 23 to the placebo group. At baseline, the mean (±SD) triglyceride level among the patients was 2630±1315 mg per deciliter, and 71% had a history of acute pancreatitis within the previous 10 years. Triglyceride levels at 6 months were significantly reduced with the 80-mg dose of olezarsen as compared with placebo (-43.5 percentage points; 95% confidence interval [CI], -69.1 to...