Lipid Clinic Heart Institute, University of São Paulo Medical School Hospital and Hospital Israelita Albert Einstein, São Paulo, Brazil.
Global Clinical Development, Amgen, Thousand Oaks, CA, USA.
Lancet Diabetes Endocrinol. 2022 Oct;10(10):732-740. doi: 10.1016/S2213-8587(22)00221-2. Epub 2022 Sep 5.
The HAUSER-RCT study showed that 24 weeks of evolocumab (a proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitor) in paediatric patients with heterozygous familial hypercholesterolaemia was safe and improved lipid parameters compared to placebo. Here, we aimed to evaluate the safety and efficacy of evolocumab in this population for an additional 80 weeks.
HAUSER-OLE was an 80-week, single-arm, open-label extension of HAUSER-RCT, a randomised controlled trial, and was conducted at 46 centres in 23 countries. Paediatric patients aged 10-17 years with heterozygous familial hypercholesterolaemia who completed 24 weeks of monthly treatment with subcutaneously administered placebo or 420 mg evolocumab in HAUSER-RCT with no serious treatment-emergent adverse events were eligible to enrol in HAUSER-OLE. All patients received open-label subcutaneous evolocumab 420 mg monthly with background statins with or without ezetimibe for 80 additional weeks. The primary endpoint was treatment-emergent adverse events. Efficacy was evaluated by changes in lipids from the baseline of HAUSER-RCT to the end of HAUSER-OLE (104 weeks). This study is registered with ClinicalTrials.gov (NCT02624869) and is now completed.
Between Sept 10, 2016, and Nov 25, 2019, 157 patients were enrolled in HAUSER-RCT and received randomised treatment; 150 continued to HAUSER-OLE, received evolocumab treatment, and were included in the full analysis set, presented here. 146 (97%) of 150 patients completed the open-label extension. The incidence of treatment-emergent adverse events in HAUSER-OLE was 70% (105 of 150). Overall, the most common treatment-emergent adverse events were nasopharyngitis (22 [15%] of 150), headache (14 [9%]), and influenza-like illness (13 [9%]). Serious treatment-emergent adverse events occurred in four (3%) of 150 patients (perforated appendicitis and peritonitis, wrist fracture, anorexia nervosa, and headache); none was considered related to evolocumab. No treatment-emergent adverse events led to treatment discontinuation. At week 80, the mean percentage change from baseline in LDL cholesterol was -35·3% (SD 28·0).
After 80 weeks of treatment, evolocumab was safe, well tolerated, and led to sustained reductions in LDL cholesterol in paediatric patients with heterozygous familial hypercholesterolaemia. When lipid goals cannot be achieved with conventional treatments, evolocumab is an effective add-on therapy in paediatric patients.
Amgen.
For the French, Spanish, Spanish, Portuguese, Italian and Dutch translations of the abstract see Supplementary Materials section.
HAUSER-RCT 研究表明，24 周的依洛尤单抗（一种前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9 [PCSK9]抑制剂）治疗杂合子家族性高胆固醇血症的儿科患者是安全的，与安慰剂相比，可改善血脂参数。在这里，我们旨在评估依洛尤单抗在这一人群中的安全性和疗效，额外治疗 80 周。
HAUSER-OLE 是一项 80 周、单臂、开放性扩展的 HAUSER-RCT，这是一项随机对照试验，在 23 个国家的 46 个中心进行。在 HAUSER-RCT 中完成 24 周每月皮下给予安慰剂或 420mg 依洛尤单抗治疗且无严重治疗出现的不良事件的 10-17 岁杂合子家族性高胆固醇血症儿科患者有资格入组 HAUSER-OLE。所有患者在 80 周内均接受每月皮下注射 420mg 依洛尤单抗联合背景他汀类药物，可加用或不加用依折麦布。主要终点为治疗出现的不良事件。从 HAUSER-RCT 的基线到 HAUSER-OLE 的结束（104 周）时，通过血脂变化来评估疗效。本研究在 ClinicalTrials.gov 注册（NCT02624869），现已完成。
2016 年 9 月 10 日至 2019 年 11 月 25 日期间，157 名患者入组 HAUSER-RCT 并接受随机治疗；150 名患者继续接受 HAUSER-OLE 治疗，并纳入本分析集，在此介绍。150 名患者中有 146 名（97%）完成了开放性扩展。HAUSER-OLE 中治疗出现的不良事件发生率为 70%（150 名中的 105 名）。总体而言，最常见的治疗出现的不良事件为鼻咽炎（22[15%]名中的 150 名）、头痛（14[9%]名）和流感样疾病（13[9%]名）。4 名（3%）的 150 名患者发生严重的治疗出现的不良事件（阑尾炎穿孔和腹膜炎、腕骨骨折、神经性厌食症和头痛）；均不认为与依洛尤单抗有关。没有治疗出现的不良事件导致治疗停止。第 80 周时，LDL 胆固醇从基线的平均百分比变化为-35.3%（SD 28.0）。
在 80 周的治疗后，依洛尤单抗是安全的，耐受性良好，并导致杂合子家族性高胆固醇血症儿科患者的 LDL 胆固醇持续降低。当常规治疗无法达到血脂目标时，依洛尤单抗是儿科患者的一种有效的附加治疗方法。
安进公司。
