Long-Term Outcomes in Real Life of Lumacaftor–Ivacaftor Treatment in Adolescents With Cystic Fibrosis

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.

Cystic fibrosis year in review 2021

“…Of note, however the French participants had an increase in FEV1pp 10 , while the US study did not, mentioning that US participants had a higher starting FEV1 compared to the phase 3 clinical trial 9 . Exacerbations were not improved in either study, while the US found no differences in hospitalizations, or PA infection 9 and the French analysis found no changes in oral or IV antibiotic usage or CT scan evaluations 10 . Improvement in FEV1pp was noted to have an inverse correlation with age at LUM/IVA initiation 10 .…”

“…Exacerbations were not improved in either study, while the US found no differences in hospitalizations, or PA infection 9 and the French analysis found no changes in oral or IV antibiotic usage or CT scan evaluations 10 . Improvement in FEV1pp was noted to have an inverse correlation with age at LUM/IVA initiation 10 . Neither study found a correlation between changes in SC and FEV1pp, BMI percentile or BMI 9,10 .…”

“…Improvement in FEV1pp was noted to have an inverse correlation with age at LUM/IVA initiation 10 . Neither study found a correlation between changes in SC and FEV1pp, BMI percentile or BMI 9,10 . This lack of correlation with SC was also seen in a single center study of 160 participants over six months.…”

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

“…Lumacaftor and ivacaftor serum levels were also not predictive of clinical response [ 33 ]. In 2021, Bui et al prospectively investigated the clinical, radiological, and metabolic response of LUM/IVA over 24 months in 40 adolescents with CF [ 35 ]. Lung function was found to increase by +5.8 percentage points 2 years after treatment initiation, while BMI Z -score and sweat chloride concentrations improved and were sustained over 24 months.…”

“…Age at LUM/IVA initiation was lower in good responders and was associated with a greater ppFEV 1 change during the 2 years of treatment. There were no significant changes in exacerbation rates, antibiotic use, or CT scan scores [ 35 ].…”