Leah A. Cohen MD , Gregory A. Ratti MD , April R. Gorman MS , Bryan Garcia MD , Christina M. Mingora MD
{"title":"elexaftor - tezacaftor - ivacaftor在囊性纤维化和既往晚期肺部疾病患者治疗开始时的长期临床疗效","authors":"Leah A. Cohen MD , Gregory A. Ratti MD , April R. Gorman MS , Bryan Garcia MD , Christina M. Mingora MD","doi":"10.1016/j.chpulm.2024.100099","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Elexacaftor-tezacaftor-ivacaftor (ETI) is associated with increased FEV<sub>1</sub>, decreased exacerbation frequency, and BMI in people with cystic fibrosis. Landmark clinical trials excluded patients with advanced lung disease as defined by FEV<sub>1</sub> < 40%. We have previously reported an improvement in % predicted FEV<sub>1</sub> of 7.9% after 3 months of ETI in people with advanced cystic fibrosis lung disease (ACFLD). The long-term effects of ETI on this cohort are unknown. This study reports the efficacy of ETI after 24 months of treatment in people with ACFLD.</div></div><div><h3>Research Question</h3><div>What are the long-term effects of ETI on people with cystic fibrosis and pre-existing advanced lung disease on lung function, BMI, and pulmonary exacerbation rates?</div></div><div><h3>Study Design and Methods</h3><div>We conducted a retrospective cohort study of adult patients with FEV<sub>1</sub> < 40% and/or other high-risk features defined by the 2019 Cystic Fibrosis Foundation lung transplant guidelines who were started on ETI between September 2019 and February 2020. Response to therapy was assessed with repeat spirometry measured at 12 and 24 months. All measurements were taken outside of an acute exacerbation. Demographics and clinical data including BMI and pulmonary exacerbation frequency were extracted from the medical record.</div></div><div><h3>Results</h3><div>A total of 57 of 64 people with ACFLD showed improved lung function with a mean change in % predicted FEV<sub>1</sub> of 6.74% (<em>P</em> ≤ .001; 95% CI, 4.25%-9.23%) between baseline and 24 months of treatment. BMI increased by a mean change of 1.55 kg/m<sup>2</sup> (<em>P</em> ≤ .001; 95% CI, 0.93-2.18 kg/m<sup>2</sup>) during this interval. The annual exacerbation rate between the year before ETI and 24 months on ETI declined with a median of 1 less per year (<em>P</em> = .0007).</div></div><div><h3>Interpretation</h3><div>People with ACFLD experienced a significant increase in lung function at 24 months on ETI, but less than those with higher baseline lung function compared with prior studies. They also had an increase in BMI and a decline in the rate of annual pulmonary exacerbations.</div></div>","PeriodicalId":94286,"journal":{"name":"CHEST pulmonary","volume":"3 1","pages":"Article 100099"},"PeriodicalIF":0.0000,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Long-Term Clinical Efficacy of Elexacaftor-Tezacaftor-Ivacaftor in People With Cystic Fibrosis and Preexisting Advanced Lung Disease at Treatment Initiation\",\"authors\":\"Leah A. Cohen MD , Gregory A. Ratti MD , April R. Gorman MS , Bryan Garcia MD , Christina M. Mingora MD\",\"doi\":\"10.1016/j.chpulm.2024.100099\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Elexacaftor-tezacaftor-ivacaftor (ETI) is associated with increased FEV<sub>1</sub>, decreased exacerbation frequency, and BMI in people with cystic fibrosis. Landmark clinical trials excluded patients with advanced lung disease as defined by FEV<sub>1</sub> < 40%. We have previously reported an improvement in % predicted FEV<sub>1</sub> of 7.9% after 3 months of ETI in people with advanced cystic fibrosis lung disease (ACFLD). The long-term effects of ETI on this cohort are unknown. This study reports the efficacy of ETI after 24 months of treatment in people with ACFLD.</div></div><div><h3>Research Question</h3><div>What are the long-term effects of ETI on people with cystic fibrosis and pre-existing advanced lung disease on lung function, BMI, and pulmonary exacerbation rates?</div></div><div><h3>Study Design and Methods</h3><div>We conducted a retrospective cohort study of adult patients with FEV<sub>1</sub> < 40% and/or other high-risk features defined by the 2019 Cystic Fibrosis Foundation lung transplant guidelines who were started on ETI between September 2019 and February 2020. Response to therapy was assessed with repeat spirometry measured at 12 and 24 months. All measurements were taken outside of an acute exacerbation. Demographics and clinical data including BMI and pulmonary exacerbation frequency were extracted from the medical record.</div></div><div><h3>Results</h3><div>A total of 57 of 64 people with ACFLD showed improved lung function with a mean change in % predicted FEV<sub>1</sub> of 6.74% (<em>P</em> ≤ .001; 95% CI, 4.25%-9.23%) between baseline and 24 months of treatment. BMI increased by a mean change of 1.55 kg/m<sup>2</sup> (<em>P</em> ≤ .001; 95% CI, 0.93-2.18 kg/m<sup>2</sup>) during this interval. The annual exacerbation rate between the year before ETI and 24 months on ETI declined with a median of 1 less per year (<em>P</em> = .0007).</div></div><div><h3>Interpretation</h3><div>People with ACFLD experienced a significant increase in lung function at 24 months on ETI, but less than those with higher baseline lung function compared with prior studies. They also had an increase in BMI and a decline in the rate of annual pulmonary exacerbations.</div></div>\",\"PeriodicalId\":94286,\"journal\":{\"name\":\"CHEST pulmonary\",\"volume\":\"3 1\",\"pages\":\"Article 100099\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CHEST pulmonary\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2949789224000655\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CHEST pulmonary","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2949789224000655","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Long-Term Clinical Efficacy of Elexacaftor-Tezacaftor-Ivacaftor in People With Cystic Fibrosis and Preexisting Advanced Lung Disease at Treatment Initiation
Background
Elexacaftor-tezacaftor-ivacaftor (ETI) is associated with increased FEV1, decreased exacerbation frequency, and BMI in people with cystic fibrosis. Landmark clinical trials excluded patients with advanced lung disease as defined by FEV1 < 40%. We have previously reported an improvement in % predicted FEV1 of 7.9% after 3 months of ETI in people with advanced cystic fibrosis lung disease (ACFLD). The long-term effects of ETI on this cohort are unknown. This study reports the efficacy of ETI after 24 months of treatment in people with ACFLD.
Research Question
What are the long-term effects of ETI on people with cystic fibrosis and pre-existing advanced lung disease on lung function, BMI, and pulmonary exacerbation rates?
Study Design and Methods
We conducted a retrospective cohort study of adult patients with FEV1 < 40% and/or other high-risk features defined by the 2019 Cystic Fibrosis Foundation lung transplant guidelines who were started on ETI between September 2019 and February 2020. Response to therapy was assessed with repeat spirometry measured at 12 and 24 months. All measurements were taken outside of an acute exacerbation. Demographics and clinical data including BMI and pulmonary exacerbation frequency were extracted from the medical record.
Results
A total of 57 of 64 people with ACFLD showed improved lung function with a mean change in % predicted FEV1 of 6.74% (P ≤ .001; 95% CI, 4.25%-9.23%) between baseline and 24 months of treatment. BMI increased by a mean change of 1.55 kg/m2 (P ≤ .001; 95% CI, 0.93-2.18 kg/m2) during this interval. The annual exacerbation rate between the year before ETI and 24 months on ETI declined with a median of 1 less per year (P = .0007).
Interpretation
People with ACFLD experienced a significant increase in lung function at 24 months on ETI, but less than those with higher baseline lung function compared with prior studies. They also had an increase in BMI and a decline in the rate of annual pulmonary exacerbations.
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