Pierre-Régis Burgel1,2,3, Isabelle Durieu3,4,5, Raphaël Chiron6, Sophie Ramel7, Isabelle Danner-Boucher8, Anne Prevotat9, Dominique Grenet10, Christophe Marguet11, Martine Reynaud-Gaubert12, Julie Macey13, Laurent Mely14, Annlyse Fanton15, Sébastien Quetant16, Lydie Lemonnier17, Jean-Louis Paillasseur18, Jennifer Da Silva1,3,19, Clémence Martin1,2,3. 1. Université de Paris, Institut Cochin, Unité 1016, Institut National de la Santé et de la Recherche Médicale, Paris, France. 2. Respiratory Medicine and Cystic Fibrosis National Reference Center, Cochin Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. 3. Cystic Fibrosis Network, European Reference Network on Rare Respiratory Diseases, Frankfurt, Germany. 4. Centre de Référence Adulte de la Mucoviscidose, Service de Médecine Interne, Hospices Civils de Lyon, Pierre Bénite, France. 5. Équipe d'Accueil 7425, Services de Santé et Recherche sur le Rendement, Université de Lyon, Lyon, France. 6. Centre de Mucoviscidose, Hôpital Arnaud de Villeneuve, Centre Hospitalier Universitaire de Montpellier, Montpellier, France. 7. Centre de Ressources et de Compétences de la Mucoviscidose, Fondation Ildys, Roscoff, France. 8. Service de Pneumologie, L'Institut Du Thorax, Centre Hospitalier Universitaire de Nantes, Nantes, France. 9. Centre de Mucoviscidose, Service de Pneumologie et Immuno-allergologie, Hôpital Calmette, Centre Hospitalier Universitaire de Lille, Université de Lille, Lille, France. 10. Service de Pneumologie, Hôpital Foch, Suresnes, France. 11. Centre des Maladies Respiratoires Pédiatriques et de la Mucoviscidose, Hospitalier Universitaire de Rouen Normandie, Université de Rouen Normandie, Équipe d'Accueil 2656, Institut National de la Santé et de la Recherche Médicale, Rouen, France. 12. Department of Respiratory Medicine and Lung Transplantation, Nord Hospital, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France. 13. Respiratory Medicine and Cystic Fibrosis Center, University Hospital Center of Bordeaux, Bordeaux, France. 14. Cystic Fibrosis Center, Renée Sabran Hospital, Giens, France. 15. Cystic Fibrosis Resource and Competence Center for Adults, Department of Pulmonary Medicine, Dijon University Hospital, France. 16. Service Hospitalo-Universitaire de Pneumologie et Physiologie, Pôle Thorax et Vaisseaux, Centre Hospitalier Universitaire de Grenoble-Alpes, La Tronche, France. 17. Association Vaincre la Mucoviscidose, Paris, France. 18. Effi-Stat, Paris, France; and. 19. Unité de Recherche Clinique, Centre d'Investigation Clinique Paris Descartes Necker-Cochin, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France.
Abstract
Rationale: Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. Objectives: To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. Methods: A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV1 (ppFEV1) <40 who initiated elexacaftor-tezacaftor-ivacaftor from December 2019 to August 2020 in France was conducted. Clinical characteristics were collected at initiation and at 1 and 3 months. Safety and effectiveness were evaluated by September 2020. National-level transplantation and mortality figures for 2020 were obtained from the French CF and transplant centers and registries. Measurements and Main Results: Elexacaftor-tezacaftor- ivacaftor was initiated in 245 patients with a median (interquartile range) ppFEV1 = 29 (24-34). The mean (95% confidence interval) absolute increase in the ppFEV1 was +15.1 (+13.8 to +16.4; P < 0.0001), and the mean (95% confidence interval) in weight was +4.2 kg (+3.9 to +4.6; P < 0.0001). The number of patients requiring long-term oxygen, noninvasive ventilation, and/or enteral tube feeding decreased by 50%, 30%, and 50%, respectively (P < 0.01). Although 16 patients were on the transplant waiting list and 37 were undergoing transplantation evaluation at treatment initiation, only 2 received a transplant, and 1 died. By September 2020, only five patients were still on the transplantation path. Compared with the previous 2 years, a twofold decrease in the number of lung transplantations in patients with CF was observed in 2020, whereas the number of deaths without transplantation remained stable. Conclusions: In patients with advanced disease, elexacaftor-tezacaftor-ivacaftor is associated with rapid clinical improvement, often leading to the indication for lung transplantation being suspended.
Rationale: Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. Objectives: To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. Methods: A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV1 (ppFEV1) <40 who initiated elexacaftor-tezacaftor-ivacaftor from December 2019 to August 2020 in France was conducted. Clinical characteristics were collected at initiation and at 1 and 3 months. Safety and effectiveness were evaluated by September 2020. National-level transplantation and mortality figures for 2020 were obtained from the French CF and transplant centers and registries. Measurements and Main Results:Elexacaftor-tezacaftor- ivacaftor was initiated in 245 patients with a median (interquartile range) ppFEV1 = 29 (24-34). The mean (95% confidence interval) absolute increase in the ppFEV1 was +15.1 (+13.8 to +16.4; P < 0.0001), and the mean (95% confidence interval) in weight was +4.2 kg (+3.9 to +4.6; P < 0.0001). The number of patients requiring long-term oxygen, noninvasive ventilation, and/or enteral tube feeding decreased by 50%, 30%, and 50%, respectively (P < 0.01). Although 16 patients were on the transplant waiting list and 37 were undergoing transplantation evaluation at treatment initiation, only 2 received a transplant, and 1 died. By September 2020, only five patients were still on the transplantation path. Compared with the previous 2 years, a twofold decrease in the number of lung transplantations in patients with CF was observed in 2020, whereas the number of deaths without transplantation remained stable. Conclusions: In patients with advanced disease, elexacaftor-tezacaftor-ivacaftor is associated with rapid clinical improvement, often leading to the indication for lung transplantation being suspended.
Authors: Eusebi Chiner-Vives; Rosa Cordovilla-Pérez; David de la Rosa-Carrillo; Marta García-Clemente; José Luis Izquierdo-Alonso; Remedios Otero-Candelera; Luis Pérez-de Llano; Jacobo Sellares-Torres; José Ignacio de Granda-Orive Journal: Arch Bronconeumol Date: 2022-04-15 Impact factor: 6.333