Elizabeth A Cromwell, Josh S Ostrenga, Don B Sanders, Wayne Morgan, Carlo Castellani, Rhonda Szczesniak, Pierre-Regis Burgel
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The evolution of forced expiratory volume in 1 s (FEV<sub>1</sub>) percentage predicted and rates of pulmonary exacerbations were analysed over the first year following ETI initiation, using a linear regression with generalised estimating equations and a negative binomial model, respectively.</p><p><strong>Results: </strong>A total of 1791 individuals aged ≥6 years with rare <i>CFTR</i> variants were eligible for ETI, corresponding to 5.2% of CFFPR participants. 815 individuals (45.5%), of which 57.9% were already treated with another CFTR modulator, initiated ETI within the first 2 years following approval. Individuals with more severe respiratory disease were more likely to initiate ETI, whereas those previously treated with another CFTR modulator or those with no private insurance coverage had less ETI initiation. ETI initiation was associated with an increase in mean FEV<sub>1</sub> % pred by +3.39 (95% CI 2.14-4.64) and a decrease in the rates of pulmonary exacerbations (adjusted rate ratio 0.55, 95% CI 0.38-0.79). These effects were greater in individuals naïve of previous CFTR modulators.</p><p><strong>Conclusions: </strong>Extension of the ETI label to rare <i>CFTR</i> variants is associated with meaningful improvements in lung function and a marked reduction in pulmonary exacerbations.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6000,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561404/pdf/","citationCount":"0","resultStr":"{\"title\":\"Impact of the expanded label for elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with no F508del variant in the USA.\",\"authors\":\"Elizabeth A Cromwell, Josh S Ostrenga, Don B Sanders, Wayne Morgan, Carlo Castellani, Rhonda Szczesniak, Pierre-Regis Burgel\",\"doi\":\"10.1183/13993003.01146-2024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Elexacaftor/tezacaftor/ivacaftor (ETI), which is approved for people with cystic fibrosis (pwCF) with a F508del variant, was further approved based on <i>in vitro</i> data in the USA for those carrying at least one of 177 rare <i>CFTR</i> (cystic fibrosis transmembrane conductance regulator) variants.</p><p><strong>Methods: </strong>PwCF, aged ≥6 years, carrying no F508del variant but with at least one of these 177 rare variants, were identified within the US Cystic Fibrosis Foundation Patient Registry (CFFPR) between 2020 and 2022. The evolution of forced expiratory volume in 1 s (FEV<sub>1</sub>) percentage predicted and rates of pulmonary exacerbations were analysed over the first year following ETI initiation, using a linear regression with generalised estimating equations and a negative binomial model, respectively.</p><p><strong>Results: </strong>A total of 1791 individuals aged ≥6 years with rare <i>CFTR</i> variants were eligible for ETI, corresponding to 5.2% of CFFPR participants. 815 individuals (45.5%), of which 57.9% were already treated with another CFTR modulator, initiated ETI within the first 2 years following approval. Individuals with more severe respiratory disease were more likely to initiate ETI, whereas those previously treated with another CFTR modulator or those with no private insurance coverage had less ETI initiation. ETI initiation was associated with an increase in mean FEV<sub>1</sub> % pred by +3.39 (95% CI 2.14-4.64) and a decrease in the rates of pulmonary exacerbations (adjusted rate ratio 0.55, 95% CI 0.38-0.79). These effects were greater in individuals naïve of previous CFTR modulators.</p><p><strong>Conclusions: </strong>Extension of the ETI label to rare <i>CFTR</i> variants is associated with meaningful improvements in lung function and a marked reduction in pulmonary exacerbations.</p>\",\"PeriodicalId\":12265,\"journal\":{\"name\":\"European Respiratory Journal\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":16.6000,\"publicationDate\":\"2024-11-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561404/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Respiratory Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1183/13993003.01146-2024\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/1 0:00:00\",\"PubModel\":\"Print\",\"JCR\":\"Q1\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Respiratory Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1183/13993003.01146-2024","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/1 0:00:00","PubModel":"Print","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
引用次数: 0
摘要
背景:Elexacaftor/tezacaftor/ivacaftor(ETI)已被批准用于F508del变体的囊性纤维化患者(pwCF),根据美国的体外数据,该药还被进一步批准用于携带177个罕见CFTR(囊性纤维化跨膜传导调节器)变体中至少一个变体的患者:方法:2020 年至 2022 年期间,在美国囊性纤维化基金会患者登记处 (CFFPR) 发现年龄≥6 岁、未携带 F508del 变异但至少携带 177 个罕见变异之一的 PwCF。研究人员分别使用线性回归广义估计方程和负二项模型分析了开始使用 ETI 后第一年的 1 秒用力呼气容积(FEV1)预测百分比和肺部恶化率的变化情况:共有1791名年龄≥6岁的罕见CFTR变异者符合ETI条件,占CFFPR参与者的5.2%。815人(45.5%)在获批后的头两年内开始接受ETI治疗,其中57.9%已经接受过另一种CFTR调节剂的治疗。呼吸系统疾病更严重的患者更有可能开始使用 ETI,而之前使用过另一种 CFTR 调节剂或没有私人保险的患者则较少开始使用 ETI。开始使用 ETI 与平均 FEV1 预测值增加 +3.39(95% CI 2.14-4.64)和肺部恶化率降低(调整后比率比为 0.55,95% CI 0.38-0.79)有关。这些效果在以前未使用过CFTR调节剂的患者中更为明显:结论:将 ETI 标签扩展到罕见的 CFTR 变异株与肺功能的显著改善和肺部恶化的明显减少有关。
Impact of the expanded label for elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with no F508del variant in the USA.
Background: Elexacaftor/tezacaftor/ivacaftor (ETI), which is approved for people with cystic fibrosis (pwCF) with a F508del variant, was further approved based on in vitro data in the USA for those carrying at least one of 177 rare CFTR (cystic fibrosis transmembrane conductance regulator) variants.
Methods: PwCF, aged ≥6 years, carrying no F508del variant but with at least one of these 177 rare variants, were identified within the US Cystic Fibrosis Foundation Patient Registry (CFFPR) between 2020 and 2022. The evolution of forced expiratory volume in 1 s (FEV1) percentage predicted and rates of pulmonary exacerbations were analysed over the first year following ETI initiation, using a linear regression with generalised estimating equations and a negative binomial model, respectively.
Results: A total of 1791 individuals aged ≥6 years with rare CFTR variants were eligible for ETI, corresponding to 5.2% of CFFPR participants. 815 individuals (45.5%), of which 57.9% were already treated with another CFTR modulator, initiated ETI within the first 2 years following approval. Individuals with more severe respiratory disease were more likely to initiate ETI, whereas those previously treated with another CFTR modulator or those with no private insurance coverage had less ETI initiation. ETI initiation was associated with an increase in mean FEV1 % pred by +3.39 (95% CI 2.14-4.64) and a decrease in the rates of pulmonary exacerbations (adjusted rate ratio 0.55, 95% CI 0.38-0.79). These effects were greater in individuals naïve of previous CFTR modulators.
Conclusions: Extension of the ETI label to rare CFTR variants is associated with meaningful improvements in lung function and a marked reduction in pulmonary exacerbations.
期刊介绍:
The European Respiratory Journal (ERJ) is the flagship journal of the European Respiratory Society. It has a current impact factor of 24.9. The journal covers various aspects of adult and paediatric respiratory medicine, including cell biology, epidemiology, immunology, oncology, pathophysiology, imaging, occupational medicine, intensive care, sleep medicine, and thoracic surgery. In addition to original research material, the ERJ publishes editorial commentaries, reviews, short research letters, and correspondence to the editor. The articles are published continuously and collected into 12 monthly issues in two volumes per year.