目的:纯合子家族性高胆固醇血症(HoFH)是一种罕见的遗传性疾病,其特征是LDL胆固醇(LDL-C)严重升高和动脉粥样硬化性心血管疾病。在关键阶段3HoFH试验(NCT03399786)中,evinacumab显着降低了HoFH患者的LDL-C。这项研究评估了evinacumab在成人和青少年HoFH患者中的长期安全性和有效性。
方法:在此开放标签中,单臂,第3阶段试验(NCT03409744),年龄≥12岁且未接受evinacumab治疗或以前曾在其他试验(evinacumab-continue)中接受过evinacumab治疗的HoFH患者每4周接受静脉内evinacumab15mg/kg稳定的降脂治疗.
结果:共纳入116例患者(成人:n=102;青少年:n=14),其中57人(49.1%)为女性。患者接受治疗的中位(范围)持续时间为104.3(28.3-196.3)周。总的来说,93例(80.2%)和27例(23.3%)患者报告了因治疗引起的不良事件(TEAE)和严重TEAE,分别。报告了2例(1.7%)死亡(均未被认为与evinacumab有关)。三名(2.6%)患者因TEAE而停药(无一例被认为与evinacumab相关)。从基线到第24周,evinacumab将平均LDL-C降低了43.6%[平均值(标准偏差,SD),在总体人群中3.4(3.2)mmol/L;成人和青少年的LDL-C平均降低为41.7%[平均值(SD),3.2(3.3)mmol/L和55.4%[平均值(SD),4.7(2.5)mmol/L],分别。
结论:在这个大的HoFH患者队列中,evinacumab总体耐受性良好,无论年龄和性别,LDL-C均显著降低.此外,evinacumab的疗效和安全性长期持续.
OBJECTIVE: Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disorder characterized by severely elevated LDL cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease. In the pivotal Phase 3 HoFH trial (NCT03399786), evinacumab significantly decreased LDL-C in patients with HoFH. This study assesses the long-term safety and efficacy of evinacumab in adult and adolescent patients with HoFH.
METHODS: In this open-label, single-arm, Phase 3 trial (NCT03409744), patients aged ≥12 years with HoFH who were evinacumab-naïve or had previously received evinacumab in other trials (evinacumab-continue) received intravenous evinacumab 15 mg/kg every 4 weeks with stable lipid-lowering therapy.
RESULTS: A total of 116 patients (adults: n = 102; adolescents: n = 14) were enrolled, of whom 57 (49.1%) were female. Patients were treated for a median (range) duration of 104.3 (28.3-196.3) weeks. Overall, treatment-emergent adverse events (TEAEs) and serious TEAEs were reported in 93 (80.2%) and 27 (23.3%) patients, respectively. Two (1.7%) deaths were reported (neither was considered related to evinacumab). Three (2.6%) patients discontinued due to TEAEs (none were considered related to evinacumab). From baseline to Week 24, evinacumab decreased mean LDL-C by 43.6% [mean (standard deviation, SD), 3.4 (3.2) mmol/L] in the overall population; mean LDL-C reduction in adults and adolescents was 41.7% [mean (SD), 3.2 (3.3) mmol/L] and 55.4% [mean (SD), 4.7 (2.5) mmol/L], respectively.
CONCLUSIONS: In this large cohort of patients with HoFH, evinacumab was generally well tolerated and markedly decreased LDL-C irrespective of age and sex. Moreover, the efficacy and safety of evinacumab was sustained over the long term.