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)
- PMID: 39242338
- DOI: 10.1016/j.jcf.2024.08.001
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)
Abstract
Background: 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.
Methods: 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).
Results: 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).
Conclusions: 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.
Keywords: CF; CFTR modulator; Cystic fibrosis; ETI; GI; MRI; elexacaftor/tezacaftor/ivacaftor; gastrointestinal; gut; magnetic resonance imaging.
Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AR, CH, FL, and ND have nothing to disclose. This work was supported by an investigator-initiated grant from Vertex Pharmaceuticals including salary support for AY and CN. CZ reports an investigator-initiated grant from Vertex Pharmaceuticals. JGM reports investigator-initiated grants from Vertex Pharmaceuticals and has received honoraria previously for lectures from Vertex, Pari and Chiesi. JGM also reports participation in monitoring or advisory board previously for Vertex, Viatris and Chiesi. GM reports investigator-initiated grants from Vertex Pharmaceuticals. GM also reports previous employment to Société Produits Nestlé during this study period. GM reports receiving support to attend conferences from Société Produits Nestlé previously. PG reports investigator-initiated grants from Vertex Pharmaceuticals paid to their institution. IS reports grants from the Rayne Foundation Fellowship. LM reports grants from Vertex Pharmaceuticals, Cystic Fibrosis Trust and Cystic Fibrosis Foundation paid to their institution. RS reports grants from Sanofi and Société Produits Nestlé paid to their institution and payments for consultation from Enterobiotix. ARS reports grants from Vertex pharmaceuticals paid to their institution and grants from the Cystic Fibrosis Trust and Cystic Fibrosis Foundation. ARS has previously been part of an advisory board from Viatris Pharmaceuticals (outside this current work). ARS and HLB hold a patent issued “Alkyl quinolones as biomarkers of Pseudomonas aeruginosa infection and uses thereof”. ARS reports membership of the Data Safety Monitoring Board of the Cystic Fibrosis Foundation. HLB reports grants from Cystic Fibrosis Trust, Cystic Fibrosis Foundation, LifeArc and is a board member and chief medical officer for MiDx(Ⓡ) company.
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