First real-world study of fetal therapy with CFTR modulators in cystic fibrosis: Report from the MODUL-CF study.

IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM
Anne-Sophie Bonnel, Tiphaine Bihouée, Mélanie Ribault, Marine Driessen, David Grèvent, Frantz Foissac, Ngoc Hoa Truong, Myriam Benhamida, Baptiste Arnouat, Roxana Borghese, Frédérique Chedevergne, Laure Couderc-Kohen, Jennifer da Silva, Dominique Grenet, Véronique Houdouin, Anais Le, Sarah Marchal, Eric Deneuville, Delphine Pouradier, Véronique Rousseau, Jean-Marc Treluyer, Arnaud Francart, Julie Steffann, Philippe Reix, Sihem Benaboud, Marie France Mamzer, Yves Ville, Clémence Martin, Pierre-Régis Burgel, Isabelle Sermet-Gaudelus
{"title":"First real-world study of fetal therapy with CFTR modulators in cystic fibrosis: Report from the MODUL-CF study.","authors":"Anne-Sophie Bonnel, Tiphaine Bihouée, Mélanie Ribault, Marine Driessen, David Grèvent, Frantz Foissac, Ngoc Hoa Truong, Myriam Benhamida, Baptiste Arnouat, Roxana Borghese, Frédérique Chedevergne, Laure Couderc-Kohen, Jennifer da Silva, Dominique Grenet, Véronique Houdouin, Anais Le, Sarah Marchal, Eric Deneuville, Delphine Pouradier, Véronique Rousseau, Jean-Marc Treluyer, Arnaud Francart, Julie Steffann, Philippe Reix, Sihem Benaboud, Marie France Mamzer, Yves Ville, Clémence Martin, Pierre-Régis Burgel, Isabelle Sermet-Gaudelus","doi":"10.1016/j.jcf.2025.03.009","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>We aimed to build a cohort of Maternal-Cystic Fibrosis (CF) fetal dyads treated in utero with Variant Specific Therapy (VST), to assess the efficacy on Meconium Ileus (MI) and potential adverse effects of treatment.</p><p><strong>Methods: </strong>Dyads were included if the foetus had a genetic diagnosis of CF and carried at least one variant responsive to VST. Standardized assessment included pre-VST Magnetic Resonance Imaging (MRI), repeated ultrasound (US), and VST drug concentrations in cord blood, maternal and infant plasma.</p><p><strong>Results: </strong>We enrolled 13 dyads. One withdrew from the study. VST therapies (Elexacaftor (ELX)/Tezacaftor (TEZ)/Ivacaftor(IVA) (ETI) n = 11, ivacaftor (IVA) n = 1) were administered to the pregnant women between 19 and 36 weeks' of gestation for a median[IQR] of 35[55] days, either as a curative indication of MI (n = 8) or as a tertiary prevention of fetal CF-related intestinal symptoms (n = 4). One foetus experienced increased bowel dilatation after ETI introduction. MRI revealed intestinal atresia. One dyad received only 2 doses. In the other 6 cases, resolution of MI was observed within 14[10] days of ETI. Fetal development and neonatal tolerance were excellent. Fecal elastase at birth was always below 200 ng/g even in the ETI breast-fed infant. Cord-to-maternal concentration yielded median ratios of 0.40 for ELX, 0.54 for IVA and 1.59 for TEZ.</p><p><strong>Conclusion: </strong>ETI administration from the third trimester of pregnancy enables MI resolution. Trans-placental transfer is high. Fetal tolerance at ETI initiation needs to be monitored by a standardized assessment.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4000,"publicationDate":"2025-03-24","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.2025.03.009","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
引用次数: 0

Abstract

Background: We aimed to build a cohort of Maternal-Cystic Fibrosis (CF) fetal dyads treated in utero with Variant Specific Therapy (VST), to assess the efficacy on Meconium Ileus (MI) and potential adverse effects of treatment.

Methods: Dyads were included if the foetus had a genetic diagnosis of CF and carried at least one variant responsive to VST. Standardized assessment included pre-VST Magnetic Resonance Imaging (MRI), repeated ultrasound (US), and VST drug concentrations in cord blood, maternal and infant plasma.

Results: We enrolled 13 dyads. One withdrew from the study. VST therapies (Elexacaftor (ELX)/Tezacaftor (TEZ)/Ivacaftor(IVA) (ETI) n = 11, ivacaftor (IVA) n = 1) were administered to the pregnant women between 19 and 36 weeks' of gestation for a median[IQR] of 35[55] days, either as a curative indication of MI (n = 8) or as a tertiary prevention of fetal CF-related intestinal symptoms (n = 4). One foetus experienced increased bowel dilatation after ETI introduction. MRI revealed intestinal atresia. One dyad received only 2 doses. In the other 6 cases, resolution of MI was observed within 14[10] days of ETI. Fetal development and neonatal tolerance were excellent. Fecal elastase at birth was always below 200 ng/g even in the ETI breast-fed infant. Cord-to-maternal concentration yielded median ratios of 0.40 for ELX, 0.54 for IVA and 1.59 for TEZ.

Conclusion: ETI administration from the third trimester of pregnancy enables MI resolution. Trans-placental transfer is high. Fetal tolerance at ETI initiation needs to be monitored by a standardized assessment.

求助全文
约1分钟内获得全文 求助全文
来源期刊
Journal of Cystic Fibrosis
Journal of Cystic Fibrosis 医学-呼吸系统
CiteScore
10.10
自引率
13.50%
发文量
1361
审稿时长
50 days
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信