Multisystemic Effects of Elexacaftor–Tezacaftor–Ivacaftor in Adults with Cystic Fibrosis and Advanced Lung Disease
Archive ouverte
Burgel, Pierre-Régis | Paillasseur, Jean-Louis | Durieu, Isabelle | Reynaud-Gaubert, Martine | Hamidfar, Rebecca | Murris-Espin, Marlène | Danner-Boucher, Isabelle | Chiron, Raphaël | Leroy, Sylvie | Douvry, Benoit | Grenet, Dominique | Mely, Laurent | Ramel, Sophie | Montcouquiol, Sylvie | Burnet, Espérie | Ouaalaya, El Hassane | Sogni, Philippe | da Silva, Jennifer | Martin, Clémence | Andrejak, Claire | Poulet, Claire | Chevalier, Marie-Chantal | Jouvenot, Marie | Marien, Caroline | Paris, Audrey | Person, Christine | Priou, Pascaline | Pernet, Didier | Richaud-Thiriez, Bénédicte | Roux-Claude, Pauline | Blanc, Nathalia | Macey, Julie | Campbell, Karine | Ruivard, Marc | Remus, Natacha | Beltramo, Guillaume | Fanton, Annlyse | Boldron-Ghaddar, Amale | Bouzioukh, Rabah | Simon, Charles | Hamidfar, Rébecca | Quetant, Sebastien | Audousset, Camille | Gicquello, Alice | Le Rouzic, Olivier | Perez, Thierry | Paris, Nicolas | Dupuy-Grasset, Magali | Languepin, Jane | Nove-Josserand, Raphaele | Reynaud, Quitterie | Coltey, Bérangère | Desmazes-Dufeu, Nadine | Gauthier, Clarisse | Rey, Jean-Baptiste | Caimmi, Davide | Chiron, Raphael | Devrait, Margot | Guillaumot, Anne | Peretti, Laura | Tiotiu, Angélica | Eschapasse, Emmanuel | Pradelli, Johana | Carlier, Nicolas | Honoré, Isabelle | Kanaan, Reem | Dury, Sandra | Ravoninjatovo, Bruno | Vigier, Clémentine | Belleguic, Chantal | Brinchault, Graziella | Barzic, Audrey | Dirou-Prigent, Anne | Le Bihan, Jean | Revert, Krista | Ropars, Thomas | Dominique, Stéphane | Marguet, Christophe | Morisse-Pradier, Hélène | Pramil, Stéphanie | Allou, Nathalie | Enaud, Laurent | Gachelin, Elsa | Huchot, Eric | Payet, Annabelle | Perisson, Caroline | Piyaraly, Saguiraly | Valois, Sophie | Kessler, Romain | Porzio, Michele | Beaumont, Laurence | de Verdiere, Sylvie Colin | Cuquemelle, Elise | de Miranda, Sandra | Roux, Antoine | Roy, Charlotte | Dupuis, Marion | Faviez, Guillaume | Labouret, Géraldine | Roditis, Léa | Cosson, Laure | Flament, Thomas | Giraut, Charlotte | Mankikian, Julie | Arnouat, Baptiste | Mousset, Gaétane | Storni, Véronique | Vigneron, Philippe
Edité par
CCSD ; American Thoracic Society -
International audience.
ationale: Limited data exist on the safety and effectiveness of elexacaftor-tezacaftor-ivacaftor (ETI) in people with cystic fibrosis (pwCF) and advanced lung disease. Objectives: To evaluate the effects of ETI in an unselected population of pwCF and advanced lung disease. Methods: A prospective observational study, including all adults aged 18 years and older with percentage predicted forced expiratory volume in 1 second (ppFEV1) ⩽ 40 who initiated ETI from December 2019 to June 2021 in France, was conducted. PwCF were followed until August 8, 2022. Results: ETI was initiated in 434 pwCF with a median ppFEV1 of 30 (interquartile range, 25-35), including 27 with severe cystic fibrosis liver disease and 183 with diabetes. PwCF were followed for a median of 587 (interquartile range, 396-728) days after ETI initiation. Discontinuation of ETI occurred in 12 (2.8%) pwCF and was due mostly to lung transplantation (n = 5) or death (n = 4). Absolute increase in ppFEV1 by a mean of +14.2% (95% confidence interval, 13.1-15.4%) occurred at 1 month and persisted throughout the study. Increase in ppFEV1 in the youngest age quartile was almost twice that of the oldest quartile (P < 0.001); body mass index < 18.5 kg/m2 was found in 38.6% at initiation versus 11.3% at 12 months (P = 0.0001). Increases in serum concentrations of vitamins A and E, but not 25-hydroxy vitamin D3, were observed. Significant reductions in the percentages of pwCF using oxygen therapy, noninvasive ventilation, nutritional support, and inhaled and systemic therapies (including antibiotics) were observed; insulin was discontinued in 12% of patients with diabetes. Conclusions: ETI is safe in pwCF and advanced lung disease, with multisystem pulmonary and extrapulmonary benefits.
