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Observational Study
. 2023 Aug 11;24(1):199.
doi: 10.1186/s12931-023-02497-0.

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  1   2 , Barry Linnane  3 , Michael Williamson  1 , Basil Elnazir  1   4 , Christopher Short  5   6 , Clare Saunders  5   6 , Laura Kirwan  7 , Rea David  1 , Mariette P C Kemner-Van de Corput  8 , Harm A W M Tiddens  1 , Jane C Davies  5   6 , Des W Cox  9   10
Affiliations
Observational Study

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 et al. Respir Res. .

Abstract

Background: Data from clinical trials of lumacaftor-ivacaftor (LUM-IVA) demonstrate improvements in lung clearance index (LCI) but not in FEV1 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 ppFEV1, 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 (AlumenA ratio) were abnormal at baseline and worsened over the course of the study. In 28 participants, the mean annual change from baseline LCI2.5 (-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 ppFEV1 (-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.

Keywords: Children; Lung clearance index; PRAGMA CF scores; Real-world studies.

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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
Participant flow diagram. a: Number of participants that had acceptable baseline and at least one follow up LCI2.5 measurement. b: Two participants left the study to enrol in industry led clinical trials. c: CT chest performed on a subgroup of participants
Fig. 2
Fig. 2
Spaghetti plots of change from baseline in %Bronchiectasis and %Disease over two years
Fig. 3
Fig. 3
Boxplots of the BA ratios over two years. Each box shows median, interquartile range and outliers for each BA ratio at baseline, year one and year two
Fig. 4
Fig. 4
The data for all remaining clinical outcomes (LCI2.5, ppFEV1, weight z-score, height z-score, BMI z-score) are presented as scatter plots along with the predicted modelled change in clinical outcomes over the study period. The change over time in clinical outcomes is expressed as an annualised slope, which is interpreted as the predicted annual change in the outcome. Study day was defined as the number of days pre/post initiation of LUM/IVA therapy
See this image and copyright information in PMC

References

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