Profiling the response to lumacaftor‐ivacaftor in children with cystic between fibrosis and new insight from a French‐Italian real‐life cohort. Issue 12 (6th September 2022)

• Record Type: Journal Article
• Authors: Cornet, Matthieu; Robin, Geneviève; Ciciriello, Fabiana; Bihouee, Tiphaine; Marguet, Christophe; Roy, Valérie; Lebourgeois, Muriel; Chedevergne, Frédérique; Bonnel, Anne Sophie; Kelly, Mairead; Reix, Philippe; Lucidi, Vincenzina; Stoven, Véronique; Sermet‐Gaudelus, Isabelle
• Is Part Of: Pediatric pulmonology. Volume 57:Issue 12(2022)
• Page Start: 2992
• Page End: 2999
• Publication Date: 2022-09-06
• Subjects: children -- lumacaftor‐ivacaftor -- principal component analysis; Pediatric respiratory diseases -- Periodicals; Pediatrics -- Periodicals; 618.922
• DOI: 10.1002/ppul.26123
• Languages: English
• ISSNs: 8755-6863

Abstract

Abstract: Introduction: Clinical trials for CFTR modulators consider mean changes of clinical status at the cohort level, and thus fail to assess the heterogeneity of the response. We aimed to study the different response profiles to lumacaftor‐ivacaftor according to age in children with cystic fibrosis (CF). Methods: A mathematical framework, including principal component analysis, data clustering, and data completion, was applied to a multicenter cohort of 112 children aged 6–18 years, treated with lumacaftor‐ivacaftor. Studied parameters at baseline and 6 months included body mass index (BMI), number of days of antibiotics (ATB), Sweat test (ST), forced expiratory volume in 1 s expressed in percentage predicted (ppFEV1 ), forced vital capacity (ppFVC), and forced expiratory flow at 25%–75% of FVC (ppFEF25–75 ). Results: Change in ppFEV1 was the most significant parameter in characterizing response heterogeneity among the 12–18‐year‐old patients. Patients with minimal changes in ppFEV1 were further separated by change in BMI and ATB course. In the 6–12‐year‐old children both BMI and ppFEV1 evolution were the most relevant. ST change was not associated with a clinical response. Conclusions: Change in ppFEV1, BMI, and ATB course are the most relevant outcomes to discriminate clinical response profiles in children treated with lumacaftor‐ivacaftor. Prepubertal and pubertal children display different response profiles. Highlights: Mathematical framework highlights different profiles of response to lumacaftor‐ivacaftor in 6–12‐ and 12–18‐year‐old children. Change in forced expiratory volume in 1 s is the most discriminant parameter in adolescents. Change in body mass index is an important parameter of the clinical response in 6–12‐year‐old children.