Lung function improvement on triple modulators: high-resolution, nationwide data from the Danish Cystic Fibrosis Cohort.

Autor:	Leo-Hansen C; Department of Infectious Diseases, Center for Cystic Fibrosis, Rigshospitalet, Copenhagen, Denmark., Faurholt-Jepsen D; Department of Infectious Diseases, Center for Cystic Fibrosis, Rigshospitalet, Copenhagen, Denmark.; Department Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Qvist T; Department of Infectious Diseases, Center for Cystic Fibrosis, Rigshospitalet, Copenhagen, Denmark., Højte C; Department of Infectious Diseases, Center for Cystic Fibrosis, Rigshospitalet, Copenhagen, Denmark., Nielsen BU; Department of Infectious Diseases, Center for Cystic Fibrosis, Rigshospitalet, Copenhagen, Denmark., Bryrup T; Department of Infectious Diseases, Center for Cystic Fibrosis, Rigshospitalet, Copenhagen, Denmark., Henriksen EH; Department of Infectious Diseases, Center for Cystic Fibrosis, Rigshospitalet, Copenhagen, Denmark., Katzenstein T; Department of Infectious Diseases, Center for Cystic Fibrosis, Rigshospitalet, Copenhagen, Denmark., Skov M; Department of Pediatrics and Adolescent Medicine, Center for Cystic Fibrosis, Rigshospitalet, Copenhagen, Denmark., Mathiesen IHM; Department of Infectious Diseases, Center for Cystic Fibrosis, Rigshospitalet, Copenhagen, Denmark., Jeppesen M; Department of Infectious Diseases, Center for Cystic Fibrosis, Aarhus University Hospital, Copenhagen, Denmark., Jensen-Fangel S; Department of Infectious Diseases, Center for Cystic Fibrosis, Aarhus University Hospital, Copenhagen, Denmark., Olesen HV; Department of Pediatrics and Adolescent Medicine, Center for Cystic Fibrosis, Aarhus University Hospital, Copenhagen, Denmark., Buchvald FF; Department of Pediatrics and Adolescent Medicine, Center for Cystic Fibrosis, Rigshospitalet, Copenhagen, Denmark., Nielsen KG; Department Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.; Department of Pediatrics and Adolescent Medicine, Center for Cystic Fibrosis, Rigshospitalet, Copenhagen, Denmark., Jimenez-Solem E; Department Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.; Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark.; Copenhagen Phase IV Unit, Center for Clinical Research and Prevention, Frederiksberg Hospital, Copenhagen, Denmark., Ritz C; National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark., Pressler T; Department of Infectious Diseases, Center for Cystic Fibrosis, Rigshospitalet, Copenhagen, Denmark., Olsen MF; Department of Infectious Diseases, Center for Cystic Fibrosis, Rigshospitalet, Copenhagen, Denmark.; Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	ERJ open research [ERJ Open Res] 2024 Dec 09; Vol. 10 (6). Date of Electronic Publication: 2024 Dec 09 (Print Publication: 2024).
DOI:	10.1183/23120541.00339-2024
Abstrakt:	Background: People living with cystic fibrosis in Denmark had early, universal access to triple modulator treatment with elexacaftor/tezacaftor/ivacaftor. Close monitoring allowed us to assess the impact of treatment on lung function and progression of lung disease in an unselected nationwide cystic fibrosis population from 6 years of age. Methods: Data were analysed using linear mixed-effect models to assess changes in levels and annual rates of change (slopes) in percent predicted (pp) forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC (ppFEF 25-75% ) between the 12 months pre-treatment and treatment periods. Subgroup analyses assessed the impact of elexacaftor/tezacaftor/ivacaftor among those with/without previous modulator treatment, normal/mild/moderate/severe lung disease at treatment initiation, children/adults and birth cohorts. Results: We included 392 people living with cystic fibrosis with a median (interquartile range) 12 (nine to 15) spirometry measurements per person. The mean (95% CI) improvement in ppFEV 1 was 13.0 (11.3-14.6) 12 months after initiation of elexacaftor/tezacaftor/ivacaftor treatment. The annual rate of change improved from -1.4 (-2.1 - -0.6) ppFEV 1 in the pre-treatment year to 2.7 (1.8-3.5) ppFEV 1 per year during treatment. Similarly, ppFVC increased by 8.0 (7.1-8.9) and FEF 25--75% by 19.5 (17.0-21.9). Conclusions: Using high-resolution data from a nationwide real-world setting, our study documents the impact of elexacaftor/tezacaftor/ivacaftor on lung function across subgroups based on age, disease severity and treatment history. These findings point towards a new period of consistent lung function improvement among people living with cystic fibrosis on elexacaftor/tezacaftor/ivacaftor. Competing Interests: Conflict of interest: T. Qvist reports receiving payment for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Vertex Pharmaceuticals in 2021–2024, outside the submitted work. Conflict of interest: S. Jensen-Fangel reports receiving payment for a lecture on pulmonary infections in the immunocompromised host from GSK, outside the submitted work; and participation on a 2023 advisory board for Takeda, outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose. (Copyright ©The authors 2024.)
Databáze:	MEDLINE
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