Elexacaftor-Tezacaftor-Ivacaftor improves exercise capacity in adolescents with cystic fibrosis

Adam John Causer, Janis Kay Shute, Michael H. Cummings, Ant Shepherd, Samual R. Wallbanks, Richard M. Pulsford, Victoria Bright, Gary Connett, Zoe Saynor

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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 (V̇O2peak) 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 V̇O2peak 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.
Original languageEnglish
JournalPediatric Pulmonology
Early online date22 Jul 2022
DOIs
Publication statusEarly online - 22 Jul 2022

Keywords

  • Elexacaftor-Tezacaftor-Iacaftor
  • cardiorespiratory fitness
  • CFTR modulator therapy
  • cystic fibrosis-transmembrane conductance regulator
  • peak oxygen uptake
  • respiratory disease

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