Lung function trajectories in children with cystic fibrosis aged 3-17 years: impact of elexacaftor-tezacaftor-ivacaftor on lung function
- 1Griffith Biostatistics Unit, Griffith Health, Griffith University, Gold Coast, Queensland, Australia. Wesley Research Institute, Brisbane, Queensland, Australia
Abstract
BackgroundElexacaftor-tezacaftor-ivacaftor (ETI) has been demonstrated to improve lung function in clinical trials; however, evidence describing effects on trajectories and whether long-term improvements are sustained (>1-year) is lacking. We estimated within-person lung clearance index (LCI) trajectories before and after ETI initiation, assessing changes in level and rate of change, alongside acute LCI change, up to three years after ETI initiation.
MethodsProspective observational study of children at a tertiary hospital. Children aged 3-17 years with [≥]2 LCI testing occasions (i) before and (ii) after starting ETI were used to describe lung function trajectories. Children with [≥]1 pre-ETI and [≥]1 post-ETI LCI occasion(s) were used to describe acute LCI change after ETI initiation. Age-adjusted LCI trajectories for time periods (i) before and (ii) after ETI initiation were estimated using linear mixed-effects models, and pre- and post-ETI LCIs were compared using paired Wilcoxon tests.
ResultsMean pre-ETI and post-ETI longitudinal changes in LCI were -0.007 (95% CI: -0.28, 0.27; n=35) and 0.12 (95% CI: -0.17, 0.41; n=20) turnovers per year, respectively. Before ETI initiation, 57% (30/53) of patients had an LCI[≥]7.1 turnovers (indicating impaired lung function), compared to 26% (14/53) post-ETI, with a median LCI difference of -0.70 (95% CI -0.84, -0.46; p<0.001) turnovers. Within-individual variability in LCI decreased post-ETI.
ConclusionsOur real-world data within a unique longitudinal study provide a comprehensive picture of ETI benefit by outlining not only acute improvement in LCI but maintained stability in LCI trajectories and improved LCI stability sustained up to three years post-initiation.
Related
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BibTeX
@misc{dyer2026lung,
title = {{Lung function trajectories in children with cystic fibrosis aged 3-17 years: impact of elexacaftor-tezacaftor-ivacaftor on lung function}},
author = {B. P. Dyer and M. Deery and R. Heyman and P. Robinson and C. Wainwright and P. Sly and R. Ware and T. Blake},
howpublished = {medRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.31.26361791},
url = {https://www.medrxiv.org/content/10.64898/2026.08.31.26361791v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Lung function trajectories in children with cystic fibrosis aged 3-17 years: impact of elexacaftor-tezacaftor-ivacaftor on lung function
AU - B. P. Dyer
AU - M. Deery
AU - R. Heyman
AU - P. Robinson
AU - C. Wainwright
AU - P. Sly
AU - R. Ware
AU - T. Blake
PY - 2026
DA - 2026/08/31
PB - medRxiv
DO - 10.64898/2026.08.31.26361791
UR - https://www.medrxiv.org/content/10.64898/2026.08.31.26361791v1
AB - BackgroundElexacaftor-tezacaftor-ivacaftor (ETI) has been demonstrated to improve lung function in clinical trials; however, evidence describing effects on trajectories and whether long-term improvements are sustained (>1-year) is lacking. We estimated within-person lung clearance index (LCI) trajectories before and after ETI initiation, assessing changes in level and rate of change, alongside acute LCI change, up to three years after ETI initiation. MethodsProspective observational study of children at a tertiary hospital. Children aged 3-17 years with [≥]2 LCI testing occasions (i) before and (ii) after starting ETI were used to describe lung function trajectories. Children with [≥]1 pre-ETI and [≥]1 post-ETI LCI occasion(s) were used to describe acute LCI change after ETI initiation. Age-adjusted LCI trajectories for time periods (i) before and (ii) after ETI initiation were estimated using linear mixed-effects models, and pre- and post-ETI LCIs were compared using paired Wilcoxon tests. ResultsMean pre-ETI and post-ETI longitudinal changes in LCI were -0.007 (95% CI: -0.28, 0.27; n=35) and 0.12 (95% CI: -0.17, 0.41; n=20) turnovers per year, respectively. Before ETI initiation, 57% (30/53) of patients had an LCI[≥]7.1 turnovers (indicating impaired lung function), compared to 26% (14/53) post-ETI, with a median LCI difference of -0.70 (95% CI -0.84, -0.46; p<0.001) turnovers. Within-individual variability in LCI decreased post-ETI. ConclusionsOur real-world data within a unique longitudinal study provide a comprehensive picture of ETI benefit by outlining not only acute improvement in LCI but maintained stability in LCI trajectories and improved LCI stability sustained up to three years post-initiation.
ER -