Abstract
Background: The combination of the CFTR corrector lumacaftor (LUM) and potentiator ivacaftor (IVA) has been labeled in France since 2015 for F508del homozygote cystic fibrosis (CF) patients over 12 years. In this real-life study, we aimed (i) to compare the changes in lung function, clinical (e.g., body mass index and pulmonary exacerbations) and radiological parameters, and in sweat chloride concentration before and after initiation of LUM/IVA treatment; (ii) to identify factors associated with response to treatment; and (iii) to assess the tolerance to treatment.Materials and Methods: In this tri-center, non-interventional, and observational cohort study, children (12–18 years old) were assessed prospectively during the 2 years of therapy, and retrospectively during the 2 years preceding treatment. Data collected and analyzed for the study were exclusively extracted from the medical electronic system records of the patients.Results: Forty adolescents aged 12.0–17.4 years at LUM/IVA initiation were included. The lung function decreased significantly during and prior to treatment and increased after LUM/IVA initiation, becoming significant after 2 years of treatment. LUM/IVA significantly improved the BMI Z-score and sweat chloride concentration. By contrast, there was no significant change in exacerbation rates, antibiotic use, or CT scan scores. Age at LUM/IVA initiation was lower in good responders and associated with greater ppFEV1 change during the 2 years of treatment. LUM/IVA was well-tolerated.Conclusion: In F508del homozygote adolescents, real-life long-term LUM/IVA improved the ppFEV1 trajectory, particularly in the youngest patients, nutritional status, and sweat chloride concentration but not exacerbation rates or radiological scores. LUM/IVA was generally well-tolerated and safe.
Highlights
Cystic fibrosis (CF) is an inherited genetic disease leading to cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction
Among the 350 adolescents with CF followed within the French South-West network of pediatric CF centers (MUCOSUD), 50 were eligible for the lumacaftor/ivacaftor association (LUM/IVA) treatment of whom one had a contraindication for LUM/IVA and seven were included in new therapies clinical trials (Figure 2)
We found a significant improvement in the ppFEV1, from worsening in the 2 years preceding treatment to a significant increase during the 2 years of the LUM/IVA therapy, in patients with ppFEV1 < 80% or body mass index (BMI) Z-score < 0 at the LUM/IVA initiation and a concomitant improvement in BMI Z-score and sweat chloride concentration after the LUM/IVA treatment
Summary
Cystic fibrosis (CF) is an inherited genetic disease leading to cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Among more than 2,000 mutations of the CFTR gene, the homozygous F508del represents the most frequent in France with a prevalence of up to 41% of patients [5] This mutation leads to a processing and trafficking defect of the CFTR protein resulting in an early degradation or a dysfunctional protein expressed into the apical membrane of the cells [1, 4, 6]. The combination of the CFTR corrector lumacaftor (LUM) and potentiator ivacaftor (IVA) has been labeled in France since 2015 for F508del homozygote cystic fibrosis (CF) patients over 12 years In this real-life study, we aimed (i) to compare the changes in lung function, clinical (e.g., body mass index and pulmonary exacerbations) and radiological parameters, and in sweat chloride concentration before and after initiation of LUM/IVA treatment; (ii) to identify factors associated with response to treatment; and (iii) to assess the tolerance to treatment
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