Impact of elexacaftor/tezacaftor/ivacaftor therapy on lung clearance index and magnetic resonance imaging in children with cystic fibrosis and one or twoF508delalleles

Abstract

BackgroundWe recently demonstrated that elexacaftor/tezacaftor/ivacaftor (ETI) improves the lung clearance index (LCI) and abnormalities in lung morphology detected by magnetic resonance imaging (MRI) in adolescent and adult patients with cystic fibrosis (CF). However, real-world data on the effect of ETI on these sensitive outcomes of lung structure and function in school-age children with CF have not been reported. The aim of this study was therefore to examine the effect of ETI on the LCI and the lung MRI score in children aged 6–11 years with CF and one or twoF508delalleles.MethodsThis prospective, observational, multicentre, post-approval study assessed the longitudinal LCI up to 12 months and the lung MRI score before and 3 months after initiation of ETI.ResultsA total of 107 children with CF including 40 heterozygous forF508deland a minimal function mutation (F/MF) and 67 homozygous forF508del(F/F) were enrolled in this study. Treatment with ETI improved the median (interquartile range (IQR)) LCI in F/MF (−1.0 (−2.0– −0.1); p<0.01) and F/F children (−0.8 (−1.9– −0.2); p<0.001) from 3 months onwards. Further, ETI improved the median (IQR) MRI global score in F/MF (−4.0 (−9.0–0.0); p<0.01) and F/F children (−3.5 (−7.3– −0.8); p<0.001).ConclusionsETI improves early abnormalities in lung ventilation and morphology in school-age children with CF and at least oneF508delallele in a real-world setting. Our results support early initiation of ETI to reduce or even prevent lung disease progression in school-age children with CF.