Titre
A longitudinal study assessing the impact of elexacaftor/tezacaftor/ivacaftor on gut transit and function in people with cystic fibrosis using magnetic resonance imaging (MRI).
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Yule, A.
Auteure/Auteur
Ng, C.
Auteure/Auteur
Recto, A.
Auteure/Auteur
Lockwood, F.
Auteure/Auteur
Dellschaft, N.S.
Auteure/Auteur
Hoad, C.L.
Auteure/Auteur
Zagoya, C.
Auteure/Auteur
Mainz, J.G.
Auteure/Auteur
Major, G.
Auteure/Auteur
Barr, H.L.
Auteure/Auteur
Gowland, P.A.
Auteure/Auteur
Stewart, I.
Auteure/Auteur
Marciani, L.
Auteure/Auteur
Spiller, R.C.
Auteure/Auteur
Smyth, A.R.
Auteure/Auteur
Liens vers les unités
ISSN
1873-5010
Statut éditorial
Publié
Date de publication
2024-09
Volume
23
Numéro
5
Première page
984
Dernière page/numéro d’article
990
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Observational Study
Publication Status: ppublish
Publication Status: ppublish
Résumé
Gastrointestinal (GI) symptoms in cystic fibrosis (CF) are common and disruptive. The effect of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on the GI tract is not fully understood. The aim was to use magnetic resonance imaging (MRI) to determine if elexacaftor/tezacaftor/ivacaftor (ETI) changed GI function and transit.
This was an 18 month prospective, longitudinal, observational study. We enrolled 24 people with CF aged 12 years or older to undergo MRI scans before starting ETI and 3, 6, and 18 months after starting ETI. The primary outcome measure was change in oro-caecal transit time (OCTT) at 6 and 18 months. Secondary outcome measures included change in small bowel water content (SBWC), change in the reduction in small bowel water content following a meal (DeltaSBWC) and change in total colonic volume (TCV).
A total of 21 participants completed MRI scans at 6 months and 11 completed at 18 months. After 18 months of ETI, median OCTT significantly reduced, from >360 min [IQR 240->360] to 240 min [IQR 180-300] (p = 0.02, Wilcoxon signed-rank). Both SBWC and DeltaSBWC increased after starting ETI. TCV reduced significantly after 18 months (p = 0.005, Friedman).
Our findings suggest an improvement in small bowel transit, small bowel response to food and a reduction in colonic volume after starting ETI. These effects may relate to CFTR activation in the small bowel. To our knowledge this is the first study to show a physiological change in GI transit and function in response to CFTR modulator use through imaging studies.
This was an 18 month prospective, longitudinal, observational study. We enrolled 24 people with CF aged 12 years or older to undergo MRI scans before starting ETI and 3, 6, and 18 months after starting ETI. The primary outcome measure was change in oro-caecal transit time (OCTT) at 6 and 18 months. Secondary outcome measures included change in small bowel water content (SBWC), change in the reduction in small bowel water content following a meal (DeltaSBWC) and change in total colonic volume (TCV).
A total of 21 participants completed MRI scans at 6 months and 11 completed at 18 months. After 18 months of ETI, median OCTT significantly reduced, from >360 min [IQR 240->360] to 240 min [IQR 180-300] (p = 0.02, Wilcoxon signed-rank). Both SBWC and DeltaSBWC increased after starting ETI. TCV reduced significantly after 18 months (p = 0.005, Friedman).
Our findings suggest an improvement in small bowel transit, small bowel response to food and a reduction in colonic volume after starting ETI. These effects may relate to CFTR activation in the small bowel. To our knowledge this is the first study to show a physiological change in GI transit and function in response to CFTR modulator use through imaging studies.
Sujets
PID Serval
serval:BIB_3D663DEB2F8C
PMID
Open Access
Oui
Date de création
2024-09-13T14:06:10.126Z
Date de création dans IRIS
2025-05-20T16:32:13Z
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Nom
39242338.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
1.27 MB
Format
Adobe PDF
PID Serval
serval:BIB_3D663DEB2F8C.P001
URN
urn:nbn:ch:serval-BIB_3D663DEB2F8C5
Somme de contrôle
(MD5):e4602c0bb2e05b9c6cdda6a846eda39e