Evinacumab治疗纯合子家族性高胆固醇血症：ELIPSE HoFH研究的意大利队列

IF 3.4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2025-04-02 DOI:10.1007/s12325-025-03160-4

Gabriella Iannuzzo, Ilenia Calcaterra, Marco Gentile, Claudia Stanzione, Francesca De Ruberto, Maria Donata Di Taranto, Giuliana Fortunato, Matteo Di Minno

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引用次数: 0

摘要

纯合子家族性高胆固醇血症（HoFH）是一种严重的罕见遗传疾病，其特征是血浆低密度脂蛋白（LDL）胆固醇水平升高。在这里，我们报告来自意大利纯合子家族性高胆固醇血症患者Evinacumab脂质研究（elisse HoFH）试验队列的数据。方法：elisse HoFH在11个国家的30个地点进行，每个国家入组2-10例患者。该研究纳入年龄≥12岁的患者，筛查时LDL胆固醇≥70 mg/dl (1.8 mmol / l)，尽管有稳定的最大耐受降脂治疗。患者随机分配evinacumab（每4周15 mg/kg）或匹配的安慰剂，为期24周，并可选择24周的开放标签延长或随访期。意大利队列包括7例分配到evinacumab的患者。结果：5例患者（男3例，女2例）接受evinacumab治疗，纳入本报告。在所有随访时间点，观察到所有患者的低密度脂蛋白胆固醇从基线水平持续大幅下降。总体而言，观察到LDL胆固醇中位数（范围）下降84.5%，从2016年的323 (203-587)mg/dl降至2019年的50.0 (13-103)mg/dl (P = 0.043)， LDL胆固醇水平稳定到2023年。总胆固醇、高密度脂蛋白（HDL）胆固醇、非高密度脂蛋白胆固醇和甘油三酯随时间显著下降。Evinacumab耐受性良好，无治疗相关不良事件报道。结论：Evinacumab可显著降低HoFH患者的LDL胆固醇水平，无论LDL受体功能如何，且低水平持续5年以上。试验注册：ClinicalTrials.gov识别码NCT03399786于2018年1月16日注册。

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Evinacumab for Homozygous Familial Hypercholesterolemia: The Italian Cohort of the ELIPSE HoFH Study

Introduction

Homozygous familial hypercholesterolemia (HoFH) is a severe rare genetic disorder characterized by elevated plasma low-density lipoprotein (LDL) cholesterol levels. Here, we report data from the Italian cohort of the Evinacumab Lipid Studies in Patients with Homozygous Familial Hypercholesterolemia (ELIPSE HoFH) trial.

Methods

ELIPSE HoFH was conducted at 30 sites in 11 countries, with 2–10 patients enrolled per country. The study included patients aged ≥ 12 years with LDL cholesterol ≥ 70 mg/dl (1.8 mmol per liter) at screening despite stable maximally tolerated lipid-lowering therapy. Patients were randomly assigned evinacumab (15 mg/kg every 4 weeks) or matching placebo for 24 weeks, with an option for a 24-week open-label extension or follow-up period thereafter. The Italian cohort included seven patients assigned to evinacumab.

Results

Five patients (3 males and 2 females) received evinacumab and were included in this report. Substantial and consistent reductions in LDL cholesterol from baseline levels were observed in all patients at all follow-up time points. Overall, an 84.5% decrease in median (range) LDL cholesterol was observed, from 323 (203–587) mg/dl in 2016 to 50.0 (13–103) mg/dl (P = 0.043) in 2019, with LDL cholesterol levels stable through 2023. Total cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, and triglycerides decreased markedly over time. Evinacumab was well tolerated, with no treatment-related adverse events reported.

Conclusion

Evinacumab substantially lowered LDL cholesterol levels in patients with HoFH regardless of the degree of LDL receptor function, with low levels sustained over 5 years of follow-up.

Trial Registration

ClinicalTrials.gov identifier NCT03399786 registered 16 January 2018.

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.