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

• Published in: ERJ open research 2024-11, Vol.10 (6), p.339
• Main Authors: Leo-Hansen, Christian, Faurholt-Jepsen, Daniel, Qvist, Tavs, Højte, Christine, Nielsen, Bibi U, Bryrup, Thomas, Henriksen, Esben H, Katzenstein, Terese, Skov, Marianne, Mathiesen, Inger H M, Jeppesen, Majbritt, Jensen-Fangel, Søren, Olesen, Hanne V, Buchvald, Frederik Fouirnaies, Nielsen, Kim Gjerum, Jimenez-Solem, Espen, Ritz, Christian, Pressler, Tacjana, Olsen, Mette F
• Format: Article
• Language: English
• Subjects: Original s
• ISSN: 2312-0541; 2312-0541
• DOI: 10.1183/23120541.00339-2024

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. 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 ), forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC (ppFEF ) 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. 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 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 in the pre-treatment year to 2.7 (1.8-3.5) ppFEV per year during treatment. Similarly, ppFVC increased by 8.0 (7.1-8.9) and FEF by 19.5 (17.0-21.9). 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.