Christian Leo-Hansen, Daniel Faurholt-Jepsen, Tavs Qvist, Christine Højte, Bibi U Nielsen, Thomas Bryrup, Esben H Henriksen, Terese Katzenstein, Marianne Skov, Inger H M Mathiesen, Majbritt Jeppesen, Søren Jensen-Fangel, Hanne V Olesen, Frederik Fouirnaies Buchvald, Kim Gjerum Nielsen, Espen Jimenez-Solem, Christian Ritz, Tacjana Pressler, Mette F Olsen
{"title":"三重调节剂改善肺功能:来自丹麦囊性纤维化队列的高分辨率全国数据","authors":"Christian Leo-Hansen, Daniel Faurholt-Jepsen, Tavs Qvist, Christine Højte, Bibi U Nielsen, Thomas Bryrup, Esben H Henriksen, Terese Katzenstein, Marianne Skov, Inger H M Mathiesen, Majbritt Jeppesen, Søren Jensen-Fangel, Hanne V Olesen, Frederik Fouirnaies Buchvald, Kim Gjerum Nielsen, Espen Jimenez-Solem, Christian Ritz, Tacjana Pressler, Mette F Olsen","doi":"10.1183/23120541.00339-2024","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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<sub>1</sub>), forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC (ppFEF<sub>25-75%</sub>) 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.</p><p><strong>Results: </strong>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<sub>1</sub> 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<sub>1</sub> in the pre-treatment year to 2.7 (1.8-3.5) ppFEV<sub>1</sub> per year during treatment. Similarly, ppFVC increased by 8.0 (7.1-8.9) and FEF<sub>25--75%</sub> by 19.5 (17.0-21.9).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"10 6","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626609/pdf/","citationCount":"0","resultStr":"{\"title\":\"Lung function improvement on triple modulators: high-resolution, nationwide data from the Danish Cystic Fibrosis Cohort.\",\"authors\":\"Christian Leo-Hansen, Daniel Faurholt-Jepsen, Tavs Qvist, Christine Højte, Bibi U Nielsen, Thomas Bryrup, Esben H Henriksen, Terese Katzenstein, Marianne Skov, Inger H M Mathiesen, Majbritt Jeppesen, Søren Jensen-Fangel, Hanne V Olesen, Frederik Fouirnaies Buchvald, Kim Gjerum Nielsen, Espen Jimenez-Solem, Christian Ritz, Tacjana Pressler, Mette F Olsen\",\"doi\":\"10.1183/23120541.00339-2024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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<sub>1</sub>), forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC (ppFEF<sub>25-75%</sub>) 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.</p><p><strong>Results: </strong>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<sub>1</sub> 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<sub>1</sub> in the pre-treatment year to 2.7 (1.8-3.5) ppFEV<sub>1</sub> per year during treatment. Similarly, ppFVC increased by 8.0 (7.1-8.9) and FEF<sub>25--75%</sub> by 19.5 (17.0-21.9).</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":11739,\"journal\":{\"name\":\"ERJ Open Research\",\"volume\":\"10 6\",\"pages\":\"\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-12-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626609/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ERJ Open Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1183/23120541.00339-2024\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ERJ Open Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1183/23120541.00339-2024","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
Lung function improvement on triple modulators: high-resolution, nationwide data from the Danish Cystic Fibrosis Cohort.
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 (FEV1), forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC (ppFEF25-75%) 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 ppFEV1 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) ppFEV1 in the pre-treatment year to 2.7 (1.8-3.5) ppFEV1 per year during treatment. Similarly, ppFVC increased by 8.0 (7.1-8.9) and FEF25--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.
期刊介绍:
ERJ Open Research is a fully open access original research journal, published online by the European Respiratory Society. The journal aims to publish high-quality work in all fields of respiratory science and medicine, covering basic science, clinical translational science and clinical medicine. The journal was created to help fulfil the ERS objective to disseminate scientific and educational material to its members and to the medical community, but also to provide researchers with an affordable open access specialty journal in which to publish their work.