Elexacaftor-Tezacaftor-Ivacaftor improves exercise capacity in adolescents with cystic fibrosis
Elexacaftor-Tezacaftor-Ivacaftor improves exercise capacity in adolescents with cystic fibrosis
Objective: Elexacaftor/Tezacaftor/Ivacaftor (Kaftrio®) is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator with the potential to improve exercise capacity. This case-series of 3 adolescents with CF aimed to investigate whether 6 weeks treatment with Kaftrio® could improve exercise capacity in CFTR modulator naive adolescents with CF.
Methods: three adolescents (14.0 ± 1.4 years) with CF (FEV1% predicted: 62.5 ± 17.1; F508del/F508del genotype) completed an exhaustive maximal cardiopulmonary exercise test on a cycle ergometer to determine peak oxygen uptake (O2peak) and measure changes in gas exchange and ventilation during exercise at 6 weeks. We also analysed wrist-worn device-based physical activity (PA) data in 2 of the 3 cases. Validated acceleration thresholds were used to quantify time spent in each PA intensity category.
Results: clinically meaningful improvements in O2peak were observed in all 3 cases (+17.6%, +52.4% and +32.9%, respectively), with improvements greatest in those with more severe lung disease and lower fitness at baseline. Although lung function increased in all cases, inconsistent changes in markers of ventilatory and peripheral muscle efficiency likely suggest different mechanisms of improvement in this case group of adolescents with CF. Device-based analysis of PA was variable, with one case increasing and one case decreasing.
Conclusion: in this case-series we have observed, for the first time, improvements in exercise capacity following 6 weeks treatment with Kaftrio®. Improvements were greatest in the presence of more severe CF lung disease and lower aerobic fitness at baseline. The mechanism(s) responsible for these changes warrant further investigation in larger trials.
Elexacaftor-Tezacaftor-Iacaftor, cardiorespiratory fitness, CFTR modulator therapy, cystic fibrosis-transmembrane conductance regulator, peak oxygen uptake, respiratory disease
2652-2658
Causer, Adam J.
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Shute, Janis K.
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Cummings, Michael H.
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Shepherd, Anthony I.
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Wallbanks, Samuel R.
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Pulsford, Richard M.
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Bright, Victoria
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Connett, Gary
55d5676c-90d8-46bf-a508-62eded276516
Saynor, Zoe L.
a4357c7d-db59-4fa5-b24f-58d2f7e74e39
17 October 2022
Causer, Adam J.
5a91c098-ffbd-4f66-841a-34a8ecae4e01
Shute, Janis K.
668c2b6d-d369-4536-8c78-7cf76f2e04c7
Cummings, Michael H.
49e830d1-aa87-4dd0-8258-35c3d5ac9c35
Shepherd, Anthony I.
7103ee4b-4fb4-41e0-8f00-9e647e15b3fb
Wallbanks, Samuel R.
153b083d-fb87-45ad-b571-517f738a2c6c
Pulsford, Richard M.
36d10809-075a-4358-b652-e9d25689b37d
Bright, Victoria
b9927700-00e1-489f-a671-27fa7d3d2995
Connett, Gary
55d5676c-90d8-46bf-a508-62eded276516
Saynor, Zoe L.
a4357c7d-db59-4fa5-b24f-58d2f7e74e39
Causer, Adam J., Shute, Janis K., Cummings, Michael H., Shepherd, Anthony I., Wallbanks, Samuel R., Pulsford, Richard M., Bright, Victoria, Connett, Gary and Saynor, Zoe L.
(2022)
Elexacaftor-Tezacaftor-Ivacaftor improves exercise capacity in adolescents with cystic fibrosis.
Pediatric Pulmonology, 57 (11), .
(doi:10.1002/ppul.26078).
Abstract
Objective: Elexacaftor/Tezacaftor/Ivacaftor (Kaftrio®) is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator with the potential to improve exercise capacity. This case-series of 3 adolescents with CF aimed to investigate whether 6 weeks treatment with Kaftrio® could improve exercise capacity in CFTR modulator naive adolescents with CF.
Methods: three adolescents (14.0 ± 1.4 years) with CF (FEV1% predicted: 62.5 ± 17.1; F508del/F508del genotype) completed an exhaustive maximal cardiopulmonary exercise test on a cycle ergometer to determine peak oxygen uptake (O2peak) and measure changes in gas exchange and ventilation during exercise at 6 weeks. We also analysed wrist-worn device-based physical activity (PA) data in 2 of the 3 cases. Validated acceleration thresholds were used to quantify time spent in each PA intensity category.
Results: clinically meaningful improvements in O2peak were observed in all 3 cases (+17.6%, +52.4% and +32.9%, respectively), with improvements greatest in those with more severe lung disease and lower fitness at baseline. Although lung function increased in all cases, inconsistent changes in markers of ventilatory and peripheral muscle efficiency likely suggest different mechanisms of improvement in this case group of adolescents with CF. Device-based analysis of PA was variable, with one case increasing and one case decreasing.
Conclusion: in this case-series we have observed, for the first time, improvements in exercise capacity following 6 weeks treatment with Kaftrio®. Improvements were greatest in the presence of more severe CF lung disease and lower aerobic fitness at baseline. The mechanism(s) responsible for these changes warrant further investigation in larger trials.
Text
Pediatric Pulmonology - 2022 - Causer - Elexacaftor Tezacaftor Ivacaftor improves exercise capacity in adolescents with
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More information
Accepted/In Press date: 25 June 2022
e-pub ahead of print date: 18 July 2022
Published date: 17 October 2022
Keywords:
Elexacaftor-Tezacaftor-Iacaftor, cardiorespiratory fitness, CFTR modulator therapy, cystic fibrosis-transmembrane conductance regulator, peak oxygen uptake, respiratory disease
Identifiers
Local EPrints ID: 493829
URI: http://eprints.soton.ac.uk/id/eprint/493829
ISSN: 8755-6863
PURE UUID: 7ae6978c-056c-4feb-b467-df11c9a227f3
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Date deposited: 13 Sep 2024 16:50
Last modified: 14 Sep 2024 02:13
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Contributors
Author:
Adam J. Causer
Author:
Janis K. Shute
Author:
Michael H. Cummings
Author:
Anthony I. Shepherd
Author:
Samuel R. Wallbanks
Author:
Richard M. Pulsford
Author:
Victoria Bright
Author:
Gary Connett
Author:
Zoe L. Saynor
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