P-R Burgel, A Orenti, E Cromwell, M Macek, H H Gutierrez, B Karadag, A Faro, J G van Rens, L Naehrlich, E Bakkeheim, S B Carr, A Lindblad, A Zolin, E Lammertyn, R Ruseckaite, M Zampoli, C A Byrnes, Lvrf da Silva-Filho, A Elbert, S Y Cheng, A L Stephenson
{"title":"CFTR变异的全球流行程度与它们对基因因子-基因因子-基因因子的响应性有关。","authors":"P-R Burgel, A Orenti, E Cromwell, M Macek, H H Gutierrez, B Karadag, A Faro, J G van Rens, L Naehrlich, E Bakkeheim, S B Carr, A Lindblad, A Zolin, E Lammertyn, R Ruseckaite, M Zampoli, C A Byrnes, Lvrf da Silva-Filho, A Elbert, S Y Cheng, A L Stephenson","doi":"10.1016/j.jcf.2025.10.007","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Elexacaftor-tezacaftor-ivacaftor (ETI) is mostly approved in people with cystic fibrosis (pwCF) with a p.Phe508del CFTR variant. The US Food and Drug Administration (FDA) approved ETI for an additional 177 rare CFTR variants and studies identified 7 non-FDA approved variants also responsive to ETI. The global impact of expanding the ETI label to rare responsive CFTR variants on the number of eligible pwCF is unknown.</p><p><strong>Methods: </strong>Data were obtained from CF registries and individual CF clinics in countries without registries. Individuals were classified according to five mutually-exclusive categories (1) at least one p.Phe508del variant (2) at least one of the 177 FDA-approved variants (3) at least one non-FDA-approved variant responsive to ETI (4) two variants resulting in no CFTR protein (5) all other variants. The first 3 groups were considered responsive to ETI, group 4 was nonresponsive and group 5 of undetermined responsiveness.</p><p><strong>Results: </strong>Data were obtained from 95,838 pwCF living in 69 countries: 78,566 (82.0 %) had at least one p.Phe508del, 6175 (6.4 %) at least one FDA-approved variants, and 2981 (3.1 %) at least one non-FDA-approved responsive variants. Two variants resulting in no CFTR protein were found in 3574 (3.7 %) and other variant combinations in 4490 (4.7 %). The prevalence of p.Phe508del ranged from 7 % to 98 % in individual countries and expanding the eligibility to responsive non-p.Phe508del variants resulted in greatest eligibility increase in countries with low p.Phe508del prevalence.</p><p><strong>Conclusion: </strong>Expanding the label of ETI to rare responsive CFTR variants will make at least 91.5 % of pwCF eligible to this disease-modifying therapy.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0000,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Global prevalence of CFTR variants with respect to their responsiveness to elexacaftor-tezacaftor-ivacaftor.\",\"authors\":\"P-R Burgel, A Orenti, E Cromwell, M Macek, H H Gutierrez, B Karadag, A Faro, J G van Rens, L Naehrlich, E Bakkeheim, S B Carr, A Lindblad, A Zolin, E Lammertyn, R Ruseckaite, M Zampoli, C A Byrnes, Lvrf da Silva-Filho, A Elbert, S Y Cheng, A L Stephenson\",\"doi\":\"10.1016/j.jcf.2025.10.007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Elexacaftor-tezacaftor-ivacaftor (ETI) is mostly approved in people with cystic fibrosis (pwCF) with a p.Phe508del CFTR variant. The US Food and Drug Administration (FDA) approved ETI for an additional 177 rare CFTR variants and studies identified 7 non-FDA approved variants also responsive to ETI. The global impact of expanding the ETI label to rare responsive CFTR variants on the number of eligible pwCF is unknown.</p><p><strong>Methods: </strong>Data were obtained from CF registries and individual CF clinics in countries without registries. Individuals were classified according to five mutually-exclusive categories (1) at least one p.Phe508del variant (2) at least one of the 177 FDA-approved variants (3) at least one non-FDA-approved variant responsive to ETI (4) two variants resulting in no CFTR protein (5) all other variants. The first 3 groups were considered responsive to ETI, group 4 was nonresponsive and group 5 of undetermined responsiveness.</p><p><strong>Results: </strong>Data were obtained from 95,838 pwCF living in 69 countries: 78,566 (82.0 %) had at least one p.Phe508del, 6175 (6.4 %) at least one FDA-approved variants, and 2981 (3.1 %) at least one non-FDA-approved responsive variants. Two variants resulting in no CFTR protein were found in 3574 (3.7 %) and other variant combinations in 4490 (4.7 %). The prevalence of p.Phe508del ranged from 7 % to 98 % in individual countries and expanding the eligibility to responsive non-p.Phe508del variants resulted in greatest eligibility increase in countries with low p.Phe508del prevalence.</p><p><strong>Conclusion: </strong>Expanding the label of ETI to rare responsive CFTR variants will make at least 91.5 % of pwCF eligible to this disease-modifying therapy.</p>\",\"PeriodicalId\":15452,\"journal\":{\"name\":\"Journal of Cystic Fibrosis\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2025-10-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Cystic Fibrosis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jcf.2025.10.007\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cystic Fibrosis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jcf.2025.10.007","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
Global prevalence of CFTR variants with respect to their responsiveness to elexacaftor-tezacaftor-ivacaftor.
Background: Elexacaftor-tezacaftor-ivacaftor (ETI) is mostly approved in people with cystic fibrosis (pwCF) with a p.Phe508del CFTR variant. The US Food and Drug Administration (FDA) approved ETI for an additional 177 rare CFTR variants and studies identified 7 non-FDA approved variants also responsive to ETI. The global impact of expanding the ETI label to rare responsive CFTR variants on the number of eligible pwCF is unknown.
Methods: Data were obtained from CF registries and individual CF clinics in countries without registries. Individuals were classified according to five mutually-exclusive categories (1) at least one p.Phe508del variant (2) at least one of the 177 FDA-approved variants (3) at least one non-FDA-approved variant responsive to ETI (4) two variants resulting in no CFTR protein (5) all other variants. The first 3 groups were considered responsive to ETI, group 4 was nonresponsive and group 5 of undetermined responsiveness.
Results: Data were obtained from 95,838 pwCF living in 69 countries: 78,566 (82.0 %) had at least one p.Phe508del, 6175 (6.4 %) at least one FDA-approved variants, and 2981 (3.1 %) at least one non-FDA-approved responsive variants. Two variants resulting in no CFTR protein were found in 3574 (3.7 %) and other variant combinations in 4490 (4.7 %). The prevalence of p.Phe508del ranged from 7 % to 98 % in individual countries and expanding the eligibility to responsive non-p.Phe508del variants resulted in greatest eligibility increase in countries with low p.Phe508del prevalence.
Conclusion: Expanding the label of ETI to rare responsive CFTR variants will make at least 91.5 % of pwCF eligible to this disease-modifying therapy.
期刊介绍：
The Journal of Cystic Fibrosis is the official journal of the European Cystic Fibrosis Society. The journal is devoted to promoting the research and treatment of cystic fibrosis. To this end the journal publishes original scientific articles, editorials, case reports, short communications and other information relevant to cystic fibrosis. The journal also publishes news and articles concerning the activities and policies of the ECFS as well as those of other societies related the ECFS.
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