Wilkinson Michael J, Bijlani Priyesha, Davidson Michael H, Duell P Barton, Horan Mary, Malloy Mary J, Newfield Ron S, Pradeep Pallavi, Shah Prediman K, Stock Eveline O, Warden Bruce A, Ito Matthew K
University of California San Diego, La Jolla (M.J.W., P.B., R.S.N.).
University of Chicago, IL (M.H.D., M.H., P.P.).
Arterioscler Thromb Vasc Biol. 2025 Jul;45(7):1310-1315. doi: 10.1161/ATVBAHA.124.322364. Epub 2025 May 29.
Homozygous familial hypercholesterolemia (HoFH) is an autosomal semidominant disorder characterized by extreme elevations in LDL-C (low-density lipoprotein cholesterol) and early-onset atherosclerotic cardiovascular disease. Evinacumab is a monoclonal antibody administered by monthly intravenous infusion that binds ANGPTL3 (angiopoietin-like 3) and when added to standard lipid-lowering therapies lowers LDL-C by ≈50% in HoFH clinical trials. Studies examining the real-world effectiveness and safety of evinacumab are limited.
We performed a retrospective study to assess the effectiveness and safety of evinacumab in patients with HoFH in clinical practice at 6 US academic medical centers. The primary end point was the percent change in LDL-C from baseline to first follow-up and to the most recent follow-up after evinacumab initiation. Secondary end points were percent change in non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, total cholesterol, HDL-C, and achievement of an LDL-C <70 mg/dL. Adverse events were recorded.
Twenty-four patients (mean age, 40 [range, 5-84] years) with HoFH were followed for a median of 48 weeks. Fifty percent were female, 66.7% had atherosclerotic cardiovascular disease, 87.5% were on a statin, 83.3% were on ezetimibe, 66.7% were on PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitors), 24% were on lomitapide, and 33.3% were undergoing lipoprotein apheresis. Significant reductions in LDL-C, non-HDL-C, total cholesterol, triglycerides, and HDL-C were observed both at the first follow-up (4 weeks) and the most recent follow-up (48 weeks); mean±SEM percent change from baseline to the most recent follow-up was as follows: LDL-C, -53.2% (±4.1); non-HDL-C, -52.7% (±3.9); triglycerides, -47.4% (±5.1); total cholesterol, -48.9% (±4.0); and HDL-C, -30.2% (±4.1); <0.001 for all. Significantly more patients achieved LDL-C <70 mg/dL after evinacumab was added. Nine (37.5%) patients reported adverse events during or following evinacumab infusions. Treatment was discontinued by 1 patient because of back pain.
Across 6 US academic medical centers, evinacumab was generally well tolerated by patients with HoFH and lowered LDL-C by ≈50%, consistent with results from clinical trials.
纯合子家族性高胆固醇血症（HoFH）是一种常染色体半显性疾病，其特征为低密度脂蛋白胆固醇（LDL-C）极度升高和早发性动脉粥样硬化性心血管疾病。依维那库单抗是一种每月静脉输注给药的单克隆抗体，可结合血管生成素样蛋白3（ANGPTL3），在HoFH临床试验中，当添加到标准降脂治疗中时，可使LDL-C降低约50%。关于依维那库单抗在现实世界中的有效性和安全性的研究有限。
我们进行了一项回顾性研究，以评估依维那库单抗在美国6家学术医疗中心临床实践中对HoFH患者的有效性和安全性。主要终点是从基线到首次随访以及依维那库单抗开始治疗后至最近一次随访时LDL-C的变化百分比。次要终点是非高密度脂蛋白胆固醇（non-HDL-C）、甘油三酯、总胆固醇、高密度脂蛋白胆固醇（HDL-C）的变化百分比以及LDL-C<70mg/dL的达成情况。记录不良事件。
24例HoFH患者（平均年龄40岁[范围5-84岁]）接受了中位48周的随访。50%为女性，66.7%患有动脉粥样硬化性心血管疾病，87.5%服用他汀类药物，83.3%服用依折麦布，66.7%服用前蛋白转化酶枯草溶菌素/kexin 9型抑制剂（PCSK9i），24%服用洛美他派，33.3%接受脂蛋白分离术。在首次随访（4周）和最近一次随访（48周）时均观察到LDL-C、non-HDL-C、总胆固醇、甘油三酯和HDL-C显著降低；从基线到最近一次随访的平均±标准误变化百分比如下：LDL-C，-53.2%（±4.1）；non-HDL-C，-52.7%（±3.9）；甘油三酯，-47.4%（±5.1）；总胆固醇，-48.9%（±4.0）；HDL-C，-30.2%（±4.1）；所有指标均P<0.001。添加依维那库单抗后，达到LDL-C<70mg/dL的患者显著增多。9例（37.5%）患者在依维那库单抗输注期间或之后报告了不良事件。1例患者因背痛停止治疗。
在美国6家学术医疗中心，HoFH患者对依维那库单抗总体耐受性良好，且LDL-C降低约50%，与临床试验结果一致。
