Impact of elexacaftor/tezacaftor/ivacaftor therapy on lung clearance index and magnetic resonance imaging in children with cystic fibrosis and one or two F508del alleles

Eur Respir J. 2024 Sep 5;64(3):2400004. doi: 10.1183/13993003.00004-2024. Print 2024 Sep.

Abstract

Background: We 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 two F508del alleles.

Methods: This 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.

Results: A total of 107 children with CF including 40 heterozygous for F508del and a minimal function mutation (F/MF) and 67 homozygous for F508del (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).

Conclusions: ETI improves early abnormalities in lung ventilation and morphology in school-age children with CF and at least one F508del allele 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.

Publication types

  • Observational Study
  • Multicenter Study

MeSH terms

  • Alleles*
  • Aminophenols* / therapeutic use
  • Benzodioxoles* / therapeutic use
  • Child
  • Cystic Fibrosis Transmembrane Conductance Regulator* / genetics
  • Cystic Fibrosis* / diagnostic imaging
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / genetics
  • Drug Combinations
  • Female
  • Homozygote
  • Humans
  • Indoles* / therapeutic use
  • Lung* / diagnostic imaging
  • Lung* / drug effects
  • Lung* / physiopathology
  • Magnetic Resonance Imaging*
  • Male
  • Mutation
  • Prospective Studies
  • Pyrazoles* / therapeutic use
  • Pyridines / therapeutic use
  • Pyrrolidines / therapeutic use
  • Quinolones* / therapeutic use

Substances

  • Aminophenols
  • Quinolones
  • Indoles
  • Benzodioxoles
  • Pyrazoles
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Drug Combinations
  • Pyridines
  • elexacaftor
  • ivacaftor
  • Pyrrolidines
  • tezacaftor