近日，西澳大利亚大学Gerald F. Watts团队研究了Plozasiran治疗持续性乳糜微粒血症患者对胰腺炎风险的影响。相关论文于2024年9月2日发表在《新英格兰医学杂志》上。

持续性乳糜微粒血症是一种遗传隐性疾病，通常由家族性乳糜微粒综合征（FCS）引起，但也有多因素的原因。这种疾病与复发性急性胰腺炎的风险有关。Plozasiran是一种小干扰RNA，可减少肝脏载脂蛋白C-III和循环甘油三酯的产生。

在一项3期临床试验中，研究组随机分配了75名患有持续性乳糜微粒血症（有或没有遗传诊断）的患者，每3个月接受一次皮下注射Plozasiran（25mg或50mg）或安慰剂，持续12个月。主要终点是10个月时空腹甘油三酯水平与基线相比的中位数百分比变化。关键次要终点是空腹甘油三酯水平从基线到10个月和12个月平均值的百分比变化，空腹载脂蛋白C-III水平从基线至10个月及12个月的变化，以及急性胰腺炎的发病率。

在基线时，甘油三酯水平的中位数为每分升2044毫克。在10个月时，25 mg plozasiran组空腹甘油三酯水平（主要终点）与基线相比的中位数变化为-80%，50 mg plozasilan组为-78%，安慰剂组为-17%（P<0.001）。关键次要终点显示，与安慰剂组相比，plozasiran组的预后更好，包括急性胰腺炎的发病率（比值比，0.17；95%置信区间，0.03至0.94；P=0.03）。各组不良事件的风险相似；最常见的不良事件是腹痛、鼻咽炎、头痛和恶心。与安慰剂组相比，Plozasiran组严重不良事件的发生率较低。一些患有糖尿病前期或糖尿病的患者在基线时出现了Plozasiran引起的高血糖。

研究结果表明，与接受安慰剂的患者相比，接受Plozasiran治疗的持续乳糜微粒血症患者的，甘油三酯水平和胰腺炎发病率显著降低。

附：英文原文

Title: Plozasiran for Managing Persistent Chylomicronemia and Pancreatitis Risk

Author: Gerald F. Watts, Robert S. Rosenson, Robert A. Hegele, Ira J. Goldberg, Antonio Gallo, Ann Mertens, Alexis Baass, Rong Zhou, Ma’an Muhsin, Jennifer Hellawell, Nicholas J. Leeper, Daniel Gaudet

Issue&Volume: 2024-09-02

Abstract:

BACKGROUND

Persistent chylomicronemia is a genetic recessive disorder that is classically caused by familial chylomicronemia syndrome (FCS), but it also has multifactorial causes. The disorder is associated with the risk of recurrent acute pancreatitis. Plozasiran is a small interfering RNA that reduces hepatic production of apolipoprotein C-III and circulating triglycerides.

METHODS

In a phase 3 trial, we randomly assigned 75 patients with persistent chylomicronemia (with or without a genetic diagnosis) to receive subcutaneous plozasiran (25 mg or 50 mg) or placebo every 3 months for 12 months. The primary end point was the median percent change from baseline in the fasting triglyceride level at 10 months. Key secondary end points were the percent change in the fasting triglyceride level from baseline to the mean of values at 10 months and 12 months, changes in the fasting apolipoprotein C-III level from baseline to 10 months and 12 months, and the incidence of acute pancreatitis.

RESULTS

At baseline, the median triglyceride level was 2044 mg per deciliter. At 10 months, the median change from baseline in the fasting triglyceride level (the primary end point) was 80% in the 25-mg plozasiran group, 78% in the 50-mg plozasiran group, and 17% in the placebo group (P<0.001). The key secondary end points showed better results in the plozasiran groups than in the placebo group, including the incidence of acute pancreatitis (odds ratio, 0.17; 95% confidence interval, 0.03 to 0.94; P=0.03). The risk of adverse events was similar across groups; the most common adverse events were abdominal pain, nasopharyngitis, headache, and nausea. Severe and serious adverse events were less common with plozasiran than with placebo. Hyperglycemia with plozasiran occurred in some patients with prediabetes or diabetes at baseline.

CONCLUSIONS

Patients with persistent chylomicronemia who received plozasiran had significantly lower triglyceride levels and a lower incidence of pancreatitis than those who received placebo.

DOI: NJ202409020000020

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2409368