Real-Life Safety and Effectiveness of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis
- 14 January 2020
- journal article
- research article
- Published by American Thoracic Society in American Journal of Respiratory and Critical Care Medicine
- Vol. 201 (2), 188-197
- https://doi.org/10.1164/rccm.201906-1227OC
Abstract
Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation. Objectives: To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (>12 yr) and adults (>18 yr) in a real-life postapproval setting. Methods: The study was conducted in the 47 CF reference centers in France. All patients who initiated lumacaftor-ivacaftor from January 1 to December 31, 2016, were eligible. Patients were evaluated for lumacaftor-ivacaftor safety and effectiveness over the first year of treatment following the French CF Learning Society's recommendations. Measurements and Main Results: Among the 845 patients (292 adolescents and 553 adults) who initiated lumacaftor-ivacaftor, 18.2% (154 patients) discontinued treatment, often owing to respiratory (48.1%, 74 patients) or nonrespiratory (27.9%, 43 patients) adverse events. In multivariable logistic regression, factors associated with increased rates of discontinuation included adult age group, percent predicted FEV1 (ppFEV1) less than 40%, and numbers of intravenous antibiotic courses during the year before lumacaftorivacaftor initiation. Patients with continuous exposure to lumacaftorivacaftor showed an absolute increase in ppFEV1 (13.67%), an increase in body mass index (10.73 kg/m(2)), and a decrease in intravenous antibiotic courses by 35%. Patients who discontinued treatment had significant decrease in ppFEV1, without improvement in body mass index or decrease in intravenous antibiotic courses. Conclusions: Lumacaftor-ivacaftorwas associated with improvement in lung disease andnutritional status inpatientswho tolerated treatment. Adults who discontinued lumacaftor-ivacaftor, often owing to adverse events, were found at high risk of clinical deterioration.Keywords
This publication has 26 references indexed in Scilit:
- Cystic fibrosisThe Lancet, 2016
- Causes of death in French cystic fibrosis patients: The need for improvement in transplantation referral strategies!Journal of Cystic Fibrosis, 2016
- From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutationsMolecular Biology of the Cell, 2016
- Response to: ‘Lumacaftor/ivacaftor for patients homozygous for Phe508del-CFTR: should we curb our enthusiasm?’ by Jones and BarryThorax, 2015
- Report of the European Respiratory Society/European Cystic Fibrosis Society task force on the care of adults with cystic fibrosisEuropean Respiratory Journal, 2015
- Lumacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508delCFTRThe New England Journal of Medicine, 2015
- Lumacaftor/ivacaftor for patients homozygous for Phe508del-CFTR: should we curb our enthusiasm?Thorax, 2015
- Future trends in cystic fibrosis demography in 34 European countriesEuropean Respiratory Journal, 2015
- A CFTR Potentiator in Patients with Cystic Fibrosis and theG551DMutationThe New England Journal of Medicine, 2011
- Exacerbation frequency and clinical outcomes in adult patients with cystic fibrosisThorax, 2011