“Shifting sands in cystic fibrosis”: impacts of CFTR modulators on reproductive health in people with cystic fibrosis and challenges related to in utero exposure
File(s)
Author(s)
Felton, Imogen
Downes, Amy
Bokobza, Idan
Weitnauer, Ladina
Davies, Jane C
Type
Journal Article
Abstract
Introduction
Mutation-specific disease modifying drugs such as the triple combination Elexacaftor/Tezacaftor/Ivacaftor (ETI), are associated with significant improvements in physical health. Reproductive health and a pursuit of parenthood are of increased relevance; a dramatic increase in childbirth rates for females with CF has already been observed.
Areas covered
Fertility in males and females with CF, and any subsequent impact of CFTR modulator therapy, is reviewed. The potential impacts of maternal use of CFTR modulator drugs on offspring health are considered, as constituent components have been found in fetal circulation in animals and humans, and the implications for maternal continuation or cessation of treatment. Clinical data are reassuring, although cases of lens opacities, and missed CF diagnoses due to false negative newborn screening results have been reported.
Expert opinion
More research and high-quality evidence are needed to characterize maternal, fetal and long-term offspring outcomes following CFTR modulator therapy use during pregnancy and breastfeeding. There is a potential therapeutic impact of targeting CFTR-related organ dysfunction in CF-fetuses via maternal-administration of CFTR modulators. Additionally, any consequences of CFTR-modulation in heterozygote carrier infant warrants urgent and collective consensus regarding ethical and clinical research programs to evaluate this discrete population.
Mutation-specific disease modifying drugs such as the triple combination Elexacaftor/Tezacaftor/Ivacaftor (ETI), are associated with significant improvements in physical health. Reproductive health and a pursuit of parenthood are of increased relevance; a dramatic increase in childbirth rates for females with CF has already been observed.
Areas covered
Fertility in males and females with CF, and any subsequent impact of CFTR modulator therapy, is reviewed. The potential impacts of maternal use of CFTR modulator drugs on offspring health are considered, as constituent components have been found in fetal circulation in animals and humans, and the implications for maternal continuation or cessation of treatment. Clinical data are reassuring, although cases of lens opacities, and missed CF diagnoses due to false negative newborn screening results have been reported.
Expert opinion
More research and high-quality evidence are needed to characterize maternal, fetal and long-term offspring outcomes following CFTR modulator therapy use during pregnancy and breastfeeding. There is a potential therapeutic impact of targeting CFTR-related organ dysfunction in CF-fetuses via maternal-administration of CFTR modulators. Additionally, any consequences of CFTR-modulation in heterozygote carrier infant warrants urgent and collective consensus regarding ethical and clinical research programs to evaluate this discrete population.
Date Issued
2024-11-21
Date Acceptance
2024-11-04
Citation
Expert Opinion on Pharmacotherapy, 2024, 25 (17), pp.2243-2252
ISSN
1465-6566
Publisher
Taylor and Francis Group
Start Page
2243
End Page
2252
Journal / Book Title
Expert Opinion on Pharmacotherapy
Volume
25
Issue
17
Copyright Statement
Copyright © 2024 Informa UK Limited, trading as Taylor & Francis Group. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Identifier
http://dx.doi.org/10.1080/14656566.2024.2426677
Publication Status
Published
Date Publish Online
2024-11-14