Real-world assessment of LCI following lumacaftor-ivacaftor initiation in adolescents and adults with cystic fibrosis

Reix, Philippe; Tatopoulos, Aurélie; Ioan, Iulia; Bourgeois, M. Le; Bui, Stéphanie; Choukroun, M.L.; Bessaci-Kabouya, K.; Gérardin, M.; Bokov, Plamen; Silva, Jennifer Da; Paillasseur, Jean-Louis; Burgel, P.-R.

doi:10.1016/j.jcf.2021.06.002

Cited by 7 publications

(7 citation statements)

References 14 publications

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“…Other real-world studies have reported improvements in ppFEV 1 in those with impaired lung function at baseline but not in those with preserved lung function [29] [43]. In the French real-world study of outcomes with LUM/IVA, adolescents with impaired pulmonary function and raised LCI values (mean 12.3) did not demonstrate improvements in LCI or ppFEV 1 over one year [44]. Similar to the clinical trials and real-world studies that included children aged 6-11 years; our study did not identify any improvement in ppFEV 1 .…”

Section: Discussionmentioning

confidence: 83%

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

McNally

Linnane

Williamson

et al. 2023

Preprint

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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 airway-artery (AA) 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.

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Section: Discussionmentioning

confidence: 83%

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

McNally

Linnane

Williamson

et al. 2023

Preprint

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“…25,30,31 Two previous observational studies showed that LUM/IVA therapy was associated with a decrease in LCI, while no significant changes were observed in ppFEV 1 . 32,33 Unfortunately, a recent real-world study by Reix et al 34 could not confirm these results in a heterogenous group of patients monitored during the first year of LUM/IVA treatment. LCI nor FEV 1 changed significantly, and discordant results between FEV 1 and LCI were observed on an individual level.…”

Section: Discussionmentioning

confidence: 92%

The short-term effects of ORKAMBI (lumacaftor/ivacaftor) on regional and distal lung structures using functional respiratory imaging

Lauwers

Belmans

Mignot

et al. 2021

Ther Adv Respir Dis

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Background: Lumacaftor/ivacaftor (LUM/IVA) has shown modest benefits in previous research, but the exact effects in the cystic fibrosis (CF) lung remain unclear. This study aims to offer novel information on the mode of action of the cystic fibrosis transmembrane conductance regulator (CFTR)-modulating drug by assessing lung structure and function using functional respiratory imaging (FRI). Methods: CF patients aged ⩾12 years homozygous for F508del were recruited in an open-label study. Before and after 12 weeks of treatment with LUM/IVA, FRI was used to visualize regional information, such as air trapping, lobar volume and airway wall volume. Secondary outcomes included the CF-CT scoring system, spirometry, the Cystic Fibrosis Questionnaire–Revised (CFQ-R) questionnaire, exercise tolerance and nutritional status. Results: Of the 12 patients enrolled in the study, 11 completed all study visits. Concerning the FRI parameters, hyperinflation of the lung decreased, indicated by a reduction in air trapping and lobar volume at expiration. Also, a decrease in airway wall volume and a redistribution of pulmonary blood volume were noted, which might be related to a decrease in mucus impaction. Airway resistance, airway volume, internal airflow distribution and aerosol deposition pattern did not show significant changes. No significant improvements were found in any of the CF-CT scores or in the spirometric parameters. Other secondary outcomes showed similar results compared with previous research. Correlations at baseline were found between FRI and conventional outcomes, including physical functioning, spirometry and CF-CT scores. Conclusions: LUM/IVA decreased lung hyperinflation in combination with a potential decrease in mucus impaction, which can be related to an improved mucociliary transport. These results indicate that several FRI parameters, reflecting regional and distal lung structures, are more sensitive to changes caused by LUM/IVA than conventional respiratory outcomes.

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“…The authors reported a substantial decrease in fecal calprotectin concentrations in 15 adolescents with CF treated for a mean of 336 days with LUM/IVA. This decrease in intestinal inflammation was not correlated with respiratory function changes, suggesting that CF-related digestive disorders may evolve independently from pulmonary disease [ 43 ]. The long-term consequences of such a decrease in intestinal inflammation have yet to be determined, particularly in terms of the risk of colorectal cancer risk in pwCF.…”

Section: Lumacaftor/ivacaftormentioning

confidence: 99%

“…The effects of LUM/IVA on the lung clearance index (LCI) were evaluated in a retrospective study by Reix et al, who also examined the clinical value of using LCI to assess lung function in comparison with ppFEV 1 at 6 and 12 months [ 43 ]. Their results showed no improvement in LCI at either time point and a mismatch between LCI and ppFEV 1 , suggesting that LCI is not an ideal outcome measure to evaluate CFTR-modulator effectiveness in adolescent and young adult pwCF with more advanced lung disease but could provide interesting indications in younger populations with milder disease [ 43 ]. These results are, however, somewhat different than recently published studies.…”

Section: Lumacaftor/ivacaftormentioning

confidence: 99%

CFTR Modulators in People with Cystic Fibrosis: Real-World Evidence in France

Regard

Martin

Burnet

et al. 2022

Cells

Self Cite

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Cystic fibrosis (CF) is a rare genetic multisystemic disease, the manifestations of which are due to mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein and can lead to respiratory insufficiency and premature death. CFTR modulators, which were developed in the past decade, partially restore CFTR protein function. Their clinical efficacy has been demonstrated in phase 3 clinical trials, particularly in terms of lung function and pulmonary exacerbations, nutritional status, and quality of life in people with gating mutations (ivacaftor), homozygous for the F508del mutation (lumacaftor/ivacaftor and tezacaftor/ivacaftor), and in those with at least one F508del mutation (elexacaftor/tezacaftor/ivacaftor). However, many questions remain regarding their long-term safety and effectiveness, particularly in patients with advanced lung disease, liver disease, renal insufficiency, or problematic bacterial colonization. The impact of CFTR modulators on other important outcomes such as concurrent treatments, lung transplantation, chest imaging, or pregnancies also warrants further investigation. The French CF Reference Network includes 47 CF centers that contribute patient data to the comprehensive French CF Registry and have conducted nationwide real-world studies on CFTR modulators. This review seeks to summarize the results of these real-world studies and examine their findings against those of randomized control trials.

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Real-world assessment of LCI following lumacaftor-ivacaftor initiation in adolescents and adults with cystic fibrosis

Cited by 7 publications

References 14 publications

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

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

The short-term effects of ORKAMBI (lumacaftor/ivacaftor) on regional and distal lung structures using functional respiratory imaging

CFTR Modulators in People with Cystic Fibrosis: Real-World Evidence in France

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