Pediatric Department, Cystic Fibrosis Pediatric Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Department of Pediatric Medicine, Meyer Children's Hospital IRCCS, Cystic Fibrosis Regional Reference Center, Florence, Italy.
Pediatr Pulmonol. 2024 Nov;59(11):2792-2799. doi: 10.1002/ppul.27125. Epub 2024 Jun 13.
Elexacaftor-tezacaftor-ivacaftor (ETI) is a highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulating therapy for people with CF and at least one F508del variant. However, there is limited data about the safety and efficacy of this therapy in pediatric populations and in real-world settings. This study aimed at evaluating the effectiveness, tolerability, and safety of ETI in children with CF.
This was a prospective observational study including all children aged 6-11 years who initiated ETI therapy between October 2022 and March 2023 at the Pediatric CF Center of Milan (Italy). Study outcomes included changes in sweat chloride concentration, FEV, LCI, body mass index (BMI), tolerance, and safety. Mean changes in study outcomes from baseline through 24 weeks were estimated using mixed-effects regression models.
The study included 34 children with CF (median age: 8.3 years). At Week 12, we observed an average decrease in LCI of 2.3 units (95% confidence interval [CI]: -3.1; -1.5). At Week 24, sweat chloride concentration decreased by 63 mEq/L (95% CI: -69; -58), FEV increased by 8.8 percentage point (95% CI: 3.7; 13.9) and BMI increased by 0.15 standard deviation scores (95% CI: 0.04; 0.25). Skin rashes appeared in 6 patients which spontaneously resolved within a few days. One month after treatment initiation, one patient experienced an elevation in liver function test results, which subsequently decreased during follow-up visits without necessitating discontinuation of therapy.
Our data indicate that ETI therapy is well tolerated by children with CF and is effective in improving signs of lung function abnormalities from early childhood.
依伐卡托与泰比卡托和艾地苯醌（ETI）是一种高效的囊性纤维化（CF）跨膜电导调节因子（CFTR）调节剂，适用于至少有一种 F508del 变体的 CF 患者。然而，关于这种治疗方法在儿科人群和真实环境中的安全性和有效性的数据有限。本研究旨在评估 ETI 在 CF 儿童中的疗效、耐受性和安全性。
这是一项前瞻性观察性研究，纳入了 2022 年 10 月至 2023 年 3 月期间在米兰儿科 CF 中心（意大利）开始接受 ETI 治疗的所有 6-11 岁儿童。研究结果包括汗液氯化物浓度、FEV1、LCI、体重指数（BMI）的变化、耐受性和安全性。采用混合效应回归模型估计从基线到 24 周的研究结果的平均变化。
该研究纳入了 34 名 CF 儿童（中位年龄：8.3 岁）。在第 12 周，我们观察到 LCI 平均下降 2.3 个单位（95%置信区间 [CI]：-3.1；-1.5）。在第 24 周，汗液氯化物浓度降低了 63 mEq/L（95% CI：-69；-58），FEV1 增加了 8.8 个百分点（95% CI：3.7；13.9），BMI 增加了 0.15 个标准差评分（95% CI：0.04；0.25）。6 名患者出现皮疹，数天后自行消退。治疗开始后 1 个月，1 名患者的肝功能检查结果升高，随后在随访期间下降，无需停药。
我们的数据表明，ETI 治疗在 CF 儿童中耐受良好，可有效改善儿童早期肺功能异常的迹象。
