Pierre-Régis Burgel1,2,3, Anne Munck4, Isabelle Durieu3,5,6, Raphaël Chiron7, Laurent Mely8, Anne Prevotat9, Marlene Murris-Espin10, Michele Porzio11, Michel Abely12, Philippe Reix13,14, Christophe Marguet15, Julie Macey16, Isabelle Sermet-Gaudelus3,17,18, Harriet Corvol19,20, Stéphanie Bui21, Lydie Lemonnier22, Clémence Dehillotte22, Jennifer Da Silva1,3,23, Jean-Louis Paillasseur24, Dominique Hubert2,3. 1. Université de Paris, Institut Cochin, INSERM U1016, Paris, France. 2. Respiratory Medicine and National Reference Cystic Fibrosis Reference Center, Cochin Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. 3. ERN-Lung CF Network. 4. Hôpital Robert Debré, AP-HP, Paris, France. 5. Centre de Référence Adulte de la Mucoviscidose, Service de Médecine Interne, Hospices Civils de Lyon, Pierre Bénite, France. 6. Université de Lyon, Équipe d'Accueil Health Services and Performance Research (HESPER) 7425, Lyon, France. 7. Cystic Fibrosis Center, Hôpital Arnaud de Villeneuve, Centre Hospitalier Universitaire de Montpellier, Université de Montpellier, Montpellier, France. 8. Hôpital Renée Sabran, Cystic Fibrosis Center, Giens, France. 9. CHU-Lille, Cystic Fibrosis Center, Service de Pneumologie et Immuno-allergologie, Hôpital Calmette and Université de Lille, Lille, France. 10. Cystic Fibrosis Center, Service de Pneumologie, Pôle des Voies Respiratoires, Hôpital Larrey, CHU de Toulouse, Toulouse, France. 11. Department of Respiratory Medicine and Cystic Fibrosis Center, Federation of Translational Medicine of Strasbourg, University Hospitals, Strasbourg, France. 12. Department of Pediatrics A and Cystic Fibrosis Center, American Memorial Hospital, Reims, France. 13. UMR 5558 CNRS, Equipe EMET, Université Claude Bernard Lyon 1, Lyon, France. 14. Cystic Fibrosis Center, Hospices Civils de Lyon, Lyon, France. 15. Pediatric Respiratory Disease and Cystic Fibrosis Center, Hospital, UNIROUEN, INSERM EA 2656, Rouen University Hospital, Université de Normandie, Rouen, France. 16. Respiratory Medicine and Cystic Fibrosis Center, CHU de Bordeaux, Bordeaux, France. 17. Pediatric Respiratory Disease and Cystic Fibrosis Center, National Reference Cystic Fibrosis Reference Center, Hôpital Necker Enfants Malades, Paris France. 18. INSERM U 1151, Institut Necker Enfants Malades, Paris, France. 19. Sorbonne Université, Centre de Recherche Saint-Antoine, Paris, France. 20. Pediatric Respiratory Disease and Cystic Fibrosis Center, Hôpital Trousseau, AP-HP, Paris, France. 21. Pediatric Respiratory Disease and Cystic Fibrosis Center and CIC 1401, CHU de Bordeaux, Bordeaux, France. 22. Association Vaincre la Mucoviscidose, Paris, France. 23. URC-CIC Paris Descartes Necker Cochin, AP-HP, Hôpital Cochin, Paris, France; and. 24. Effi-stat, Paris, France.
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 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.
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.
Entities:
Keywords:
cystic fibrosis; lumacaftor–ivacaftor; postmarketing study
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