학술논문
Profiling the response to lumacaftor-ivacaftor in children with cystic between fibrosis and new insight from a French-Italian real-life cohort.
Document Type
Academic Journal
Author
Cornet M; Institut Necker-Enfants Malades, Paris, France.; Robin G; Laboratoire de Mathematiques et Modelisation d'Evry, Evry, France.; Ciciriello F; Ospedale Pediatrico Bambino Gesu, Roma, Italy.; Bihouee T; Centre Hospitalier Universitaire de Nantes, Nantes, France.; Marguet C; Hôpital Necker Enfants Malades, Paris, France.; Roy V; Mines Paris - PSL, Paris, France.; Lebourgeois M; Hôpital Necker Enfants Malades, Paris, France.; Chedevergne F; Hôpital Necker Enfants Malades, Paris, France.; Bonnel AS; Hôpital Necker Enfants Malades, Paris, France.; Kelly M; Institut Necker-Enfants Malades, Paris, France.; Reix P; Hospices Civils de Lyon, Lyon, France.; Lucidi V; Ospedale Pediatrico Bambino Gesu, Roma, Italy.; Stoven V; Mines Paris - PSL, Paris, France.; Sermet-Gaudelus I; Institut Necker-Enfants Malades, Paris, France.
Source
Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8510590 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1099-0496 (Electronic) Linking ISSN: 10990496 NLM ISO Abbreviation: Pediatr Pulmonol Subsets: MEDLINE
Subject
Language
English
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 (ppFEF 25-75 ).
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 ppFEV 1 were further separated by change in BMI and ATB course. In the 6-12-year-old children both BMI and ppFEV 1 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.
(© 2022 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)
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 (ppFEV
Results: Change in ppFEV
Conclusions: Change in ppFEV
(© 2022 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)