Work

Long-term impact of elexacaftor/tezacaftor/ivacaftor on small and large airways in people with cystic fibrosis aged ≥6 years: 24-month real-world evidence from the German Cystic Fibrosis Registry

Year: 2025

Type: article

Abstract: Background While studies have consistently reported improvements in lung function during elexacaftor/tezacaftor/ivacaftor (ETI) therapy for people with cystic fibrosis (pwCF), individual response predictors remain poorly understood and there is limited real-world data relating to children aged 6–11 years. Methods Lung function data from the German CF Registry 2020–2024 were analysed before and up to 24 months after ETI therapy initiation in adults, adolescents and children aged ≥6 years. Data were stratified for percent predicted forced expiratory volume in 1 s (ppFEV 1 ) increase during therapy (<5% versus >5%), underlying mutation and pre-treatment disease severity. Findings Data from 2375 pwCF were analysed. After starting ETI, ppFEV 1 increased most in adolescents with baseline ppFEV 1 >40–60% (median increase 16.8–20.2%); the corresponding increase in adults with the same initial lung function was 11.2–11.5%. After an initial increase, ppFEV 1 remained stable for 24 months in all age groups. No predictors for greater improvement (>5% ppFEV 1 gain) were identified but pwCF with normal ppFEV 1 before ETI therapy had smaller increases during treatment. Forced mid-expiratory flow at 25–75% of forced vital capacity increased to a similar extent in children and adolescents (+13%) and adults (+9.5%). Interpretation Our real-world data showed significant improvements in lung function, including large and small airways, during 24 months’ ETI therapy in pwCF aged ≥6 years. Notable improvements, particularly in small airways, were observed even in children and adolescents with normal ppFEV 1 before ETI. These findings underscore the importance of early ETI therapy initiation to prevent irreversible lung damage.

Source: ERJ Open Research

DOI: 10.1183/23120541.00813-2025