Efficacy and safety of using Elexacaftor/Tezacaftor/Ivacaftor in the treatment of children with cystic fibrosis: real-world evidence from Brazil

IF 3 4区医学 Q1 PEDIATRICS

Jornal de pediatria Pub Date : 2025-09-01 Epub Date: 2025-06-25 DOI:10.1016/j.jped.2025.05.007

Guilherme da Silva Martins , Carolina Rambo , Gabriela Spessatto , Maitê Milagres Saab , Bruno Hernandes David João , Aline Didoni Fajardo , Juliana Gonçalves Primon , Thalita Gonçalves Picciani , Roberta Corrêa da Cunha , Herberto José Chong-Neto , Carlos Roberto Lebarbenchon Massignan , Luiz Vicente Ribeiro Ferreira da Silva-Filho , Carlos Antônio Riedi , Nelson Augusto Rosário Filho , Débora Carla Chong-Silva

{"title":"Efficacy and safety of using Elexacaftor/Tezacaftor/Ivacaftor in the treatment of children with cystic fibrosis: real-world evidence from Brazil","authors":"Guilherme da Silva Martins , Carolina Rambo , Gabriela Spessatto , Maitê Milagres Saab , Bruno Hernandes David João , Aline Didoni Fajardo , Juliana Gonçalves Primon , Thalita Gonçalves Picciani , Roberta Corrêa da Cunha , Herberto José Chong-Neto , Carlos Roberto Lebarbenchon Massignan , Luiz Vicente Ribeiro Ferreira da Silva-Filho , Carlos Antônio Riedi , Nelson Augusto Rosário Filho , Débora Carla Chong-Silva","doi":"10.1016/j.jped.2025.05.007","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Cystic fibrosis (CF) treatment has evolved significantly with the development of CFTR modulators, particularly elexacaftor/tezacaftor/ivacaftor (ETI). This study aimed to evaluate in a real-life context, the efficacy, safety and tolerability of ETI in children and adolescents with CF at a national reference center in Brazil.</div></div><div><h3>Methods</h3><div>A cohort of 39 patients (mean age: 11.7 years) who had been using ETI for at least three months were evaluated. Anthropometric data, pulmonary function, sweat chloride concentration, pulmonary exacerbations, antibiotic use, and liver function were assessed over a follow-up period of up to 17 months.</div></div><div><h3>Results</h3><div>Significant improvements were observed in weight Z-score at three months (<em>p</em> = 0.046) and six months (<em>p</em> = 0.018), as well as absolute weight gain (<em>p</em> < 0.001). Height showed absolute growth, but no significant changes in Z-scores. Sweat chloride concentration decreased by 52.8 mmol/L (<em>p</em> < 0.001). Pulmonary exacerbations and antibiotic use significantly declined (<em>p</em> < 0.001 for both). Despite limitations in spirometry data collection, FEV1 values showed a median increase of 6 percentage points. Oropharyngeal swab cultures for <em>Pseudomonas aeruginosa</em> positivity dropped from 43.6 % to 5.1 %. Safety assessments showed a transient rise in alkaline phosphatase (<em>p</em> = 0.011), but no significant hepatotoxicity. The most common adverse events were increased respiratory secretions (25.6 %) and abdominal pain (15.4 %). One temporary treatment suspension and one dose reduction occurred, but no patient required permanent discontinuation.</div></div><div><h3>Conclusions</h3><div>ETI demonstrated effectiveness in improving weight gain, reducing pulmonary exacerbations, and significantly lowering sweat chloride concentration. The treatment was well-tolerated, with a favorable safety profile. These findings align with existing literature, supporting ETI's role as a transformative therapy in pediatric CF management.</div></div>","PeriodicalId":14867,"journal":{"name":"Jornal de pediatria","volume":"101 5","pages":"Article 101420"},"PeriodicalIF":3.0000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Jornal de pediatria","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0021755725000981","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/25 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PEDIATRICS","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

Cystic fibrosis (CF) treatment has evolved significantly with the development of CFTR modulators, particularly elexacaftor/tezacaftor/ivacaftor (ETI). This study aimed to evaluate in a real-life context, the efficacy, safety and tolerability of ETI in children and adolescents with CF at a national reference center in Brazil.

Methods

A cohort of 39 patients (mean age: 11.7 years) who had been using ETI for at least three months were evaluated. Anthropometric data, pulmonary function, sweat chloride concentration, pulmonary exacerbations, antibiotic use, and liver function were assessed over a follow-up period of up to 17 months.

Results

Significant improvements were observed in weight Z-score at three months (p = 0.046) and six months (p = 0.018), as well as absolute weight gain (p < 0.001). Height showed absolute growth, but no significant changes in Z-scores. Sweat chloride concentration decreased by 52.8 mmol/L (p < 0.001). Pulmonary exacerbations and antibiotic use significantly declined (p < 0.001 for both). Despite limitations in spirometry data collection, FEV1 values showed a median increase of 6 percentage points. Oropharyngeal swab cultures for Pseudomonas aeruginosa positivity dropped from 43.6 % to 5.1 %. Safety assessments showed a transient rise in alkaline phosphatase (p = 0.011), but no significant hepatotoxicity. The most common adverse events were increased respiratory secretions (25.6 %) and abdominal pain (15.4 %). One temporary treatment suspension and one dose reduction occurred, but no patient required permanent discontinuation.

Conclusions

ETI demonstrated effectiveness in improving weight gain, reducing pulmonary exacerbations, and significantly lowering sweat chloride concentration. The treatment was well-tolerated, with a favorable safety profile. These findings align with existing literature, supporting ETI's role as a transformative therapy in pediatric CF management.

查看原文本刊更多论文

ELEXACAFTOR/Tezacaftor/Ivacaftor治疗囊性纤维化儿童的有效性和安全性：来自巴西的真实世界证据

目的：囊性纤维化（CF）的治疗随着CFTR调节剂，特别是elexexaftor /tezacaftor/ivacaftor （ETI）的发展而发生了重大变化。本研究旨在巴西国家参考中心评估ETI治疗CF儿童和青少年的有效性、安全性和耐受性。方法：对39例使用ETI至少3个月的患者（平均年龄：11.7岁）进行队列评估。在长达17个月的随访期间评估人体测量数据、肺功能、汗液氯化物浓度、肺恶化、抗生素使用和肝功能。结果：在3个月（p = 0.046）和6个月（p = 0.018）体重z评分以及绝对体重增加（p ）方面观察到显著改善。结论：ETI在改善体重增加、减少肺部恶化和显著降低汗液氯化物浓度方面表现出有效性。治疗耐受性良好，具有良好的安全性。这些发现与现有文献一致，支持ETI在儿童CF治疗中的变革性治疗作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Jornal de pediatria 医学-小儿科

CiteScore

5.60

自引率

3.00%

发文量

审稿时长

43 days

期刊介绍： Jornal de Pediatria is a bimonthly publication of the Brazilian Society of Pediatrics (Sociedade Brasileira de Pediatria, SBP). It has been published without interruption since 1934. Jornal de Pediatria publishes original articles and review articles covering various areas in the field of pediatrics. By publishing relevant scientific contributions, Jornal de Pediatria aims at improving the standards of pediatrics and of the healthcare provided for children and adolescents in general, as well to foster debate about health.