Abstract
Elexacaftor/Tezacaftor/Ivacaftor (ETI) therapy has significantly improved clinical outcomes in people with cystic fibrosis (PwCF) carrying at least one Phe508del CFTR mutation. However, real-world evidence on the safety and effectiveness of ETI in pediatric populations remains limited, particularly in children with more severe disease phenotypes who are often excluded from clinical trials. We analyzed clinical, functional, and microbiological data from pediatric CF patients aged 6-17 years treated with ETI between October 2022 and March 2024. Lung function (ppFEV(1), ppFVC), nutritional status (BMI, BMI z-score), sweat chloride concentration (SwCl), quality of life (CFQ-R), pulmonary exacerbations (PEx), and airway pathogens were assessed at baseline and after 6-12 months. Adverse events (AEs) and therapy discontinuations were also recorded. Twenty-four patients (n = 10 aged 6-11 years; n = 14 aged 12-17 years) were included. At 12 months, mean ppFEV(1) increased by 15% (p = 0.013), BMI by 2.4 kg/m(2) (p = 0.16), BMI weight z-score by 0.33 (p = 0.63), and height z-score by -0.33 (p = 0.72), SwCl decreased by 46 mmol/L (p < 0.001), and CFQ-R respiratory domain improved by 14 points (p < 0.001). PEx rates decreased by 27.6% after 12 months. Reductions in airway pathogen prevalence, particularly Staphylococcus aureus and Pseudomonas aeruginosa, were observed. AEs occurred in 14.8% (n = 4) of patients, were mild-to-moderate, and resolved with dose reduction. ETI therapy was associated with marked improvements in lung function, nutritional status, and quality of life, along with reductions in PEx and airway pathogens, in a real-world pediatric CF cohort. These findings support ETI use in this population, with careful AE monitoring and dose adjustment when needed.