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

2019; American Thoracic Society; Volume: 201; Issue: 2 Linguagem: Inglês

10.1164/rccm.201906-1227oc

1535-4970

Pierre‐Régis Burgel, À. Munck, I. Durieu, R. Chiron, Laurent Mély, Anne Prévötat, M. Murris‐Espin, Michele Porzio, M. Abély, Philippe Reix, Christophe Marguet, Julie Macey, Isabelle Sermet‐Gaudelus, Harriet Corvol, S. Bui, Lydie Lemonnier, Clémence Dehillotte, Jennifer Da Silva, Jean-Louis Paillasseur, D. Hubert, J. Mounard, Claire Poulet, Cinthia Rames, Christine Person, Françoise Troussier, T. Urban, Marie‐Laure Dalphin, Jean-Claude Dalphin, D. Pernet, Bénédicte Richaud-Thiriez, S. Bui, Michaël Fayon, Julie Macey-Caro, Karine Campbell, Muriel Laurans, Corinne Borderon, M Héraud, A. Labbé, Sylvie Montcouquiol, Laurence Bassinet, Natascha Remus, Annlyse Fanton, Anne Houzel-Charavel, Frédéric Huet, S. Bui, Amale Boldron-Ghaddar, Manuëla Scalbert, Laurent Mély, B. Camara, C. Llerena, Isabelle Pin, S. Quétant, Aurélie Cottereau, A. Deschildre, Alice Gicquello, T. Pérez, L. Stervinou-Wémeau, C. Thumerelle, B Wallaert, Nathalie Wizla, J. Languepin, Céline Ménétrey, M. Dupuy-Grasset, Lucie Bazus, Clélia Buchs, V. Jubin, Marie‐Christine Werck‐Gallois, Catherine Mainguy, Thomas Perrin, Philippe Reix, Agnès Toutain-Rigolet, I. Durieu, S. Durupt, Quitterie Reynaud, R. Nové-Josserand, Mélisande Baravalle‐Einaudi, Bérangère Coltey, Nadine Dufeu, J.‐C. Dubus, Nathalie Stremler, Davide Caimmi, R. Chiron, Yves Billon, J. Derelle, Sébastien Kieffer, Anne-Sophie Pichon, Cyril Schweitzer, Aurélie Tatopoulos, Sarah Abbes, Tiphaine Bihouée, Isabelle Danner‐Boucher, Valérie David, A. Haloun, Adrien Tissot, Sylvie Leroy, C. Bailly-Piccini, Annick Clément, Harriet Corvol, Aline Tamalet, Pierre‐Régis Burgel, Isabelle Honoré, D. Hubert, Reem Kanaan, C. Martín, Cécile Bailly, Frédérique Chedevergne, J. de Blic, Brigitte Fauroux, Murielle Le Bourgeois, Isabelle Sermet‐Gaudelus, Bertrand Delaisi, M. Gérardin, À. Munck, M. Abély, Bruno Ravoninjatovo, Chantal Belleguic, B. Desrues, Graziella Brinchault, M. Dagorne, Eric Deneuville, Sylvaine Lefeuvre, Anne Dirou, Jean Le Bihan, Sophie Ramel, S. Dominique, Christophe Marguet, Annabelle Payet, Romain Kessler, Michele Porzio, Vincent Rosner, Laurence Weiss, Sandra de Miranda, Dominique Grenet, Abdoul Hamid, C. Picard, François Brémont, A. Didier, Géraldine Labouret, M. Mittaine, M. Murris‐Espin, L. Têtu, Laure Cosson, C. Giraut, Anne-Cécile Henriet, Julie Mankikian, Sophie Marchand, Sandrine Hugé, V. Storni, Emmanuelle Coirier-Duet,

Tracheal and airway disorders

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.