Real-Life Safety and Effectiveness of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis

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.