Pierre-Régis Burgel1, Isabelle Durieu2, Raphaël Chiron3, Laurent Mely4, Anne Prevotat5, Marlene Murris-Espin6, Michele Porzio7, Michel Abely8, Philippe Reix9, Christophe Marguet10, Julie Macey11, Isabelle Sermet-Gaudelus12, Harriet Corvol13, Stéphanie Bui14, Tiphaine Biouhee15, Dominique Hubert16, Anne Munck17, Lydie Lemonnier18, Clémence Dehillotte18, Jennifer Da Silva19, Jean-Louis Paillasseur20, Clémence Martin21. 1. Université de Paris, Institut Cochin, Paris, France; Respiratory Medicine and National Reference Cystic Fibrosis Reference Center, Cochin Hospital; Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France; ERN-Lung CF network. Electronic address: pierre-regis.burgel@aphp.fr. 2. ERN-Lung CF network; Centre de référence Adulte de la Mucoviscidose, Service de médecine interne, Hospices civils de Lyon, F-69495, Pierre Bénite, France; Université de Lyon, Équipe d'Accueil Health Services and Performance Research (HESPER) 7425, F-69003 Lyon, France. 3. Cystic Fibrosis Center, Hôpital Arnaud de Villeneuve, Centre Hospitalier Universitaire de Montpellier, Univ Montpellier, France. 4. Hôpital Renée Sabran, Cystic Fibrosis Center, Giens, France. 5. CHU-Lille Cystic Fibrosis Center Service de Pneumologie et Immuno-allergologie, Hôpital Calmette and Univ. Lille, Lille, France. 6. Cystic Fibrosis Center Service de Pneumologie Pôle des Voies Respiratoires, Hôpital Larrey CHU de Toulouse, Toulouse, France. 7. Department of Respiratory Medicine and Cystic Fibrosis Center, Federation of Translational Medicine of Strasbourg (FMTS), University Hospitals, Strasbourg, France. 8. Department of Pediatrics A and Cystic Fibrosis Center, American Memorial Hospital, Reims, France. 9. UMR 5558 CNRS Equipe EMET Université Claude Bernard Lyon 1 Lyon, France Cystic Fibrosis Center, Hospices Civils de Lyon, Lyon, France. 10. Pediatric Respiratory Disease and Cystic Fibrosis Center, Hospital UNIROUEN Inserm EA 2656, Rouen University Hospital Normandie Univ, Rouen, France. 11. Respiratory Medicine and Cystic Fibrosis Center, CHU de Bordeaux, Bordeaux, France. 12. ERN-Lung CF network; Pediatric Respiratory Disease and Cystic Fibrosis Center National Reference Cystic Fibrosis Reference Center, Hôpital Necker Enfants Malades, Paris France; INSERM U 1151, Institut Necker Enfants Malades, Paris, France. 13. Sorbonne Université, Centre de Recherche Saint-Antoine (CRSA), Paris, France; Pediatric Respiratory Disease and Cystic Fibrosis Center, Hôpital Trousseau, APHP, Paris, France. 14. Pediatric Respiratory Disease and Cystic Fibrosis Center and CIC 1401, CHU de Bordeaux, Bordeaux, France. 15. Pediatric CF Center, Nantes University Hospital, Nantes, France. 16. Respiratory Medicine and National Reference Cystic Fibrosis Reference Center, Cochin Hospital; Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France; ERN-Lung CF network. 17. Hôpital Robert Debré, AP-HP, Paris, France. 18. Association Vaincre la Mucoviscidose, Paris, France. 19. Université de Paris, Institut Cochin, Paris, France; ERN-Lung CF network; URC-CIC Paris Descartes Necker Cochin, AP-HP, Hôpital Cochin, Paris, France. 20. Effi-stat, Paris, France. 21. Université de Paris, Institut Cochin, Paris, France; Respiratory Medicine and National Reference Cystic Fibrosis Reference Center, Cochin Hospital; Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France; ERN-Lung CF network.
Abstract
BACKGROUND: Phase 3 trials have demonstrated the safety and efficacy of lumacaftor-ivacaftor (LUMA-IVA) in patients with cystic fibrosis (CF) homozygous for the Phe508del CFTR mutation and percent predicted forced expiratory volume in 1 s (ppFEV1) between 40 and 90. Marketing authorizations have been granted for patients at all levels of ppFEV1. METHODS: To evaluate the safety and effectiveness of LUMA-IVA over the first year of treatment in patients with ppFEV1<40 or ppFEV1≥90 in comparison with those with ppFEV1 [40-90[. Analysis of data collected during a real world study, which included all patients aged ≥12 years who started LUMA-IVA in 2016 across all 47 French CF centers. RESULTS: 827 patients were classified into 3 subgroups according to ppFEV1 at treatment initiation (ppFEV1<40, n = 121; ppFEV1 [40-90[, n = 609; ppFEV1≥90, n = 97). Treatment discontinuation rate was higher in ppFEV1<40 patients (28.9%) than in those with ppFEV1 [40-90[(16.4%) or ppFEV1≥90 (17.5%). In patients with uninterrupted treatment, significant increase in ppFEV1 occurred in the ppFEV1 [40-90[subgroup (+2.9%, P<0.001), and in those ppFEV1<40 (+0.5%, P = 0.03) but not in those with ppFEV1≥90 (P = 0.46). Compared with the year prior to initiation, the number of days of intravenous antibiotics were reduced in all subgroups, although 72% of patients with ppFEV1<40 still experienced at least one exacerbation/year under LUMA-IVA. Comparable increase in body mass index was seen in the three subgroups. CONCLUSION: Phe508del homozygous CF patients benefit from LUMA-IVA at all levels of baseline lung function, but the characteristics and magnitude of the response vary depending on ppFEV1 at baseline.
BACKGROUND: Phase 3 trials have demonstrated the safety and efficacy of lumacaftor-ivacaftor (LUMA-IVA) in patients with cystic fibrosis (CF) homozygous for the Phe508del CFTR mutation and percent predicted forced expiratory volume in 1 s (ppFEV1) between 40 and 90. Marketing authorizations have been granted for patients at all levels of ppFEV1. METHODS: To evaluate the safety and effectiveness of LUMA-IVA over the first year of treatment in patients with ppFEV1<40 or ppFEV1≥90 in comparison with those with ppFEV1 [40-90[. Analysis of data collected during a real world study, which included all patients aged ≥12 years who started LUMA-IVA in 2016 across all 47 French CF centers. RESULTS: 827 patients were classified into 3 subgroups according to ppFEV1 at treatment initiation (ppFEV1<40, n = 121; ppFEV1 [40-90[, n = 609; ppFEV1≥90, n = 97). Treatment discontinuation rate was higher in ppFEV1<40 patients (28.9%) than in those with ppFEV1 [40-90[(16.4%) or ppFEV1≥90 (17.5%). In patients with uninterrupted treatment, significant increase in ppFEV1 occurred in the ppFEV1 [40-90[subgroup (+2.9%, P<0.001), and in those ppFEV1<40 (+0.5%, P = 0.03) but not in those with ppFEV1≥90 (P = 0.46). Compared with the year prior to initiation, the number of days of intravenous antibiotics were reduced in all subgroups, although 72% of patients with ppFEV1<40 still experienced at least one exacerbation/year under LUMA-IVA. Comparable increase in body mass index was seen in the three subgroups. CONCLUSION: Phe508del homozygous CF patients benefit from LUMA-IVA at all levels of baseline lung function, but the characteristics and magnitude of the response vary depending on ppFEV1 at baseline.
Authors: Scott H Donaldson; Beth L Laube; Peter Mogayzel; Timothy E Corcoran; Joseph M Pilewski; Agathe Ceppe; Jihong Wu; Pradeep G Bhambhvani; Felix Ratjen; Scott D Sagel; J P Clancy; Steven M Rowe; William D Bennett Journal: J Cyst Fibros Date: 2021-05-31 Impact factor: 5.482
Authors: Clémence Martin; Camille Legeai; Lucile Regard; Christelle Cantrelle; Richard Dorent; Nicolas Carlier; François Kerbaul; Pierre-Régis Burgel Journal: Am J Respir Crit Care Med Date: 2022-03-01 Impact factor: 21.405
Authors: Francesca Saluzzo; Luca Riberi; Barbara Messore; Nicola Ivan Loré; Irene Esposito; Elisabetta Bignamini; Virginia De Rose Journal: Cells Date: 2022-04-06 Impact factor: 6.600