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 lumacaftor–ivacaftor initiation. Patients with continuous exposure to lumacaftor–ivacaftor showed an absolute increase in ppFEV1 (+3.67%), an increase in body mass index (+0.73 kg/m2), 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–ivacaftor was associated with improvement in lung disease and nutritional status in patients who tolerated treatment. Adults who discontinued lumacaftor–ivacaftor, often owing to adverse events, were found at high risk of clinical deterioration.