The clinical impact of Lumacaftor-Ivacaftor on structural lung disease and lung function in children aged 6-11 with cystic fibrosis in a real-world setting

Paul McNally, Barry Linnane, Michael Williamson, Basil Elnazir, Christopher Short, Clare Saunders, Laura Kirwan, Rea David, Mariette P.C. Kemner-Van de Corput, Harm A.W.M. Tiddens, Jane C. Davies, Des W. Cox*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Background: Data from clinical trials of lumacaftor-ivacaftor (LUM-IVA) demonstrate improvements in lung clearance index (LCI) but not in FEV 1 in children with Cystic Fibrosis (CF) aged 6–11 years and homozygous for the Phe508del mutation. It is not known whether LUM/IVA use in children can impact the progression of structural lung disease. We sought to determine the real-world impact of LUM/IVA on lung structure and function in children aged 6–11 years. Methods: This real-world observational cohort study was conducted across four paediatric sites in Ireland over 24-months using spirometry-controlled CT scores and LCI as primary outcome measures. Children commencing LUM-/IVA as part of routine care were included. CT scans were manually scored with the PRAGMA CF scoring system and analysed using the automated bronchus-artery (BA) method. Secondary outcome measures included rate of change of ppFEV 1, nutritional indices and exacerbations requiring hospitalisation. Results: Seventy-one participants were recruited to the study, 31 of whom had spirometry-controlled CT performed at baseline, and after one year and two years of LUM/IVA treatment. At two years there was a reduction from baseline in trapped air scores (0.13 to 0.07, p = 0.016), but an increase from baseline in the % bronchiectasis score (0.84 to 1.23, p = 0.007). There was no change in overall % disease score (2.78 to 2.25, p = 0.138). Airway lumen to pulmonary artery ratios (A lumenA ratio) were abnormal at baseline and worsened over the course of the study. In 28 participants, the mean annual change from baseline LCI 2.5 (-0.055 (-0.61 to 0.50), p = 0.85) measurements over two years were not significant. Improvements from baseline in weight (0.10 (0.06 to 0.15, p < 0.0001), height (0.05 (0.02 to 0.09), p = 0.002) and BMI (0.09 (0.03 to 0.15) p = 0.005) z-scores were seen with LUM/IVA treatment. The mean annual change from baseline ppFEV 1 (-2.45 (-4.44 to 2.54), p = 0.66) measurements over two years were not significant. Conclusion: In a real-world setting, the use of LUM/IVA over two years in children with CF aged 6–11 resulted in improvements in air trapping on CT but worsening in bronchiectasis scores. Our results suggest that LUM/IVA use in this age group improves air trapping but does not prevent progression of bronchiectasis over two years of treatment.

Original languageEnglish
Article number199
Number of pages1
JournalRespiratory Research
Issue number1
Publication statusPublished - Dec 2023

Bibliographical note

Funding Information:
Funding was provided by Children’s Health Foundation, Dublin through a National Children’s Research Centre innovation grant and Vertex pharmaceuticals (IIS-2017-106550).

Funding Information:
Professor Jane Davies is supported by the National Institutes of Health Research through the Imperial Biomedical Research Centre, the Royal Brompton Clinical Research Facility and a Senior Investigator Award. The remaining authors declare no competing interests.

Publisher Copyright:
© 2023, BioMed Central Ltd., part of Springer Nature.


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