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

Stéphanie Bui; Alexandra Masson; Raphaël Enaud; Léa Roditis; Gaël Dournes; François Galode; Cyrielle Collet; Emmanuel Mas; Jeanne Languepin; Michael Fayon; Fabien Beaufils; Marie Mittaine

doi:10.3389/fped.2021.744705

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

Front Pediatr. 2021 Nov 15:9:744705. doi: 10.3389/fped.2021.744705. eCollection 2021.

Authors

Stéphanie Bui¹, Alexandra Masson², Raphaël Enaud^{1

3}, Léa Roditis⁴, Gaël Dournes³, François Galode¹, Cyrielle Collet¹, Emmanuel Mas⁴, Jeanne Languepin², Michael Fayon^{1

3}, Fabien Beaufils^{1

3}, Marie Mittaine⁴

Affiliations

¹ Bordeaux University Hospital, Hôpital Pellegrin-Enfants, Paediatric Cystic Fibrosis Reference Center (CRCM), Centre d'Investigation Clinique (CIC 1401), Bordeaux, France.
² Limoges University Hospital, Paediatric Cystic Fibrosis Reference Center (CRCM), Limoges, France.
³ Bordeaux University, Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, Radiology, Bordeaux, France.
⁴ Toulouse University Hospital, Paediatric Cystic Fibrosis Reference Center (CRCM), Department of Pediatric-pulmonology, Toulouse, France.

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.

Keywords: CFTR corrector; CFTR potentiator; child; cystic fibrosis; lung function testing; nutritional status; sweat chloride.