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)

Yule, Alexander; Ng, Christabella; Recto, Arantxa; Lockwood, Florence; Dellschaft, Neele S; Hoad, Caroline L; Zagoya, Carlos; Mainz, Jochen G; Major, Giles; Barr, Helen L; Gowland, Penny A; Stewart, Iain; Marciani, Luca; Spiller, Robin C; Smyth, Alan R

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.

Citation

Yule, A., Ng, C., Recto, A., Lockwood, F., Dellschaft, N. S., Hoad, C. L., Zagoya, C., Mainz, J. G., Major, G., Barr, H. L., Gowland, P. A., Stewart, I., Marciani, L., Spiller, R. C., & Smyth, A. R. (2024). 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). Journal of Cystic Fibrosis, 23(5), 984-990. https://doi.org/10.1016/j.jcf.2024.08.001

• Journal Article Type: Article
• Acceptance Date: Aug 4, 2024
• Online Publication Date: Sep 5, 2024
• Publication Date: Sep 5, 2024
• Deposit Date: May 12, 2025
• Publicly Available Date: May 13, 2025
• Journal: Journal of Cystic Fibrosis
• Print ISSN: 1569-1993
• Electronic ISSN: 1873-5010
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 23
• Issue: 5
• Pages: 984-990
• DOI: https://doi.org/10.1016/j.jcf.2024.08.001
• Public URL: https://nottingham-repository.worktribe.com/output/39177652
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S1569199324008270?via%3Dihub
• Additional Information: This article is maintained by: Elsevier; Article Title: 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); Journal Title: Journal of Cystic Fibrosis; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.jcf.2024.08.001; Content Type: article; Copyright: © 2024 The Author(s). Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.