Department of Pediatrics, West China Second Hospital, Sichuan University, Chengdu 610041, China.
Department of Pediatrics, West China Xiamen Hospital of Sichuan University, Xiamen 361022, China.
Medicina (Kaunas). 2024 Oct 8;60(10):1646. doi: 10.3390/medicina60101646.
: The proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab are recently developed promising drugs used for treatment of familial hypercholesterolemia (FH). This systematic review and meta-analysis aimed to thoroughly evaluate the efficacy and safety of evolocumab and alirocumab among pediatric patients with FH. : A comprehensive search was conducted in PubMed, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov from inception through July 2024 to identify primary interventional studies among pediatric patients with FH. Meta-analyses were performed if appropriate. Statistics were analyzed using Review Manager version 5.4 and Stata version 16.0. : Fourteen articles reporting nine unique studies were included. There were three randomized controlled trials (RCTs) assessing evolocumab or alirocumab involving a total of 320 pediatric patients, one cross-over trial and five single-arm or observational studies. Pooled results showed significant efficacy of evolocumab/alirocumab in reducing low-density lipoprotein cholesterol (LDL-C) (weighted mean difference [WMD]: -37.92%, 95% confidence interval [CI]: -43.06% to -32.78%; I = 0.0%, = 0.60), apolipoprotein B (WMD: -33.67%, 95% CI: -38.12% to -29.22%; I = 0.0%, = 0.71), and also lipoprotein(a) (WMD: -16.94%, 95% CI: -26.20% to -7.69%; I = 0.0%, = 0.71) among pediatric patients with FH. The efficacies of evolocumab/alirocumab on LDL-C reduction within pediatric patients with heterozygous FH (HeFH) were consistent between studies, whereas in patients with homozygous FH (HoFH), it varied dramatically. Pediatric patients with the null/null variant may respond to the treatment. PCSK9 inhibitors were generally well tolerated within most pediatric patients, in line with previous studies among adult populations. : The PCSK9 inhibitors evolocumab/alirocumab significantly reduced LDL-C and some other lipid parameters, such as apolipoprotein B, in pediatric patients with HeFH. These drugs may be appropriate as a potential therapy for pediatric patients with HoFH who cannot achieve LDL-C targets with other treatments. Evolocumab/alirocumab was generally well tolerated in the pediatric population.
: 前蛋白转化酶枯草溶菌素 9（PCSK9）抑制剂依洛尤单抗和阿利西尤单抗是最近开发的用于治疗家族性高胆固醇血症（FH）的有前途的药物。本系统评价和荟萃分析旨在全面评估依洛尤单抗和阿利西尤单抗在 FH 儿科患者中的疗效和安全性。: 从研究开始到 2024 年 7 月，我们在 PubMed、Embase、CENTRAL（Cochrane 对照试验中心注册库）和 ClinicalTrials.gov 进行了全面检索，以确定 FH 儿科患者的主要干预性研究。如果合适，进行了荟萃分析。使用 Review Manager 版本 5.4 和 Stata 版本 16.0 分析统计数据。: 纳入了 14 篇报告 9 项独特研究的文章。其中 3 项随机对照试验（RCT）评估了依洛尤单抗或阿利西尤单抗，共纳入 320 名儿科患者，1 项交叉试验和 5 项单臂或观察性研究。汇总结果显示，依洛尤单抗/阿利西尤单抗在降低 LDL-C（加权均数差[WMD]：-37.92%，95%置信区间[CI]：-43.06%至-32.78%；I = 0.0%， = 0.60）、载脂蛋白 B（WMD：-33.67%，95%CI：-38.12%至-29.22%；I = 0.0%， = 0.71）和脂蛋白（a）（WMD：-16.94%，95%CI：-26.20%至-7.69%；I = 0.0%， = 0.71）方面均有显著疗效 FH 儿科患者。依洛尤单抗/阿利西尤单抗在杂合子 FH（HeFH）儿科患者中的 LDL-C 降低效果在研究间一致，而在纯合子 FH（HoFH）患者中差异显著。携带 null/null 变异的儿科患者可能对治疗有反应。PCSK9 抑制剂在大多数儿科患者中通常具有良好的耐受性，与成人人群中的先前研究一致。: PCSK9 抑制剂依洛尤单抗/阿利西尤单抗可显著降低 HeFH 儿科患者的 LDL-C 和其他一些脂质参数，如载脂蛋白 B。这些药物可能适合作为其他治疗方法不能达到 LDL-C 目标的 HoFH 儿科患者的潜在治疗方法。依洛尤单抗/阿利西尤单抗在儿科人群中通常具有良好的耐受性。
