Multisystemic Effects of Elexacaftor-Tezacaftor-Ivacaftor in Adults with Cystic Fibrosis and Advanced Lung Disease.
Abstract
Rationale: 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.
Overview publication
| Title | Multisystemic Effects of Elexacaftor-Tezacaftor-Ivacaftor in Adults with Cystic Fibrosis and Advanced Lung Disease. |
| Date | 2024-07-01 |
| Issue name | Annals of the American Thoracic Society |
| Issue number | v21.7:1053-1064 |
| DOI | 10.1513/AnnalsATS.202312-1065OC |
| PubMed | 38579175 |
| Authors | |
| Info | Participating Investigators of the French Cystic Fibrosis Reference Network Study Group, Andrejak C, Poulet C, Chevalier MC, Jouvenot M, Marien C, Paris A, Person C, Priou P, Pernet D, Richaud-Thiriez B, Roux-Claude P, Blanc N, Macey J, Campbell K, Montcouquiol S, Ruivard M, Remus N, Douvry B, Beltramo G, Fanton A, Boldron-Ghaddar A, Bouzioukh R, Mely L, Simon C, Hamidfar R, Quetant S, Audousset C, Gicquello A, Le Rouzic O, Perez T, Paris N, Dupuy-Grasset M, Languepin J, Durieu I, Nove-Josserand R, Reynaud Q, Coltey B, Desmazes-Dufeu N, Gauthier C, Rey JB, Reynaud-Gaubert M, Caimmi D, Chiron R, Devrait M, Guillaumot A, Peretti L, Tiotiu A, Danner-Boucher I, Eschapasse E, Tissot, Leroy S, Pradelli J, Burgel PR, Carlier N, Honoré I, Kanaan R, Martin C, Dury S, Ravoninjatovo B, Vigier C, Belleguic C, Brinchault G, Barzic A, Dirou-Prigent A, Le Bihan J, Ramel S, Revert K, Ropars T, Dominique S, Marguet C, Morisse-Pradier H, Pramil S, Allou N, Enaud L, Gachelin E, Huchot E, Payet A, Perisson C, Piyaraly S, Valois S, Kessler R, Porzio M, Beaumont L, de Verdiere SC, Cuquemelle E, De Miranda S, Grenet D, Roux A, Roy C, Dupuis M, Faviez G, Labouret G, Murris-Espin M, Roditis L, Cosson L, Flament T, Giraut C, Mankikian J, Arnouat B, Mousset G, Storni V, Vigneron P |
| Keywords | cystic fibrosis transmembrane conductance regulator modulators, real-word evidence, severe cystic fibrosis liver disease |
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