The long-term effect of elexacaftor/tezacaftor/ivacaftor on cardiorespiratory fitness in adolescent patients with cystic fibrosis: a pilot observational study.

Stastna N; Department of Pulmonology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
Hrabovska L;Homolka P; Homola L; Svoboda M; Brat K;Fila L;

BMC pulmonary medicine [BMC Pulm Med] 2024 May 28; Vol. 24 (1), pp. 260.
Date of Electronic Publication: 2024 May 28.

Background: Physical activity is a crucial demand on cystic fibrosis treatment management. The highest value of oxygen uptake (VO 2peak ) is an appropriate tool to evaluate the physical activity in these patients. However, there are several other valuable CPET parameters describing exercise tolerance (W peak , VO 2VT1 , VO 2VT2, VO 2 /HR peak , etc.), and helping to better understand the effect of specific treatment (V E , V T , V D /V T etc.). Limited data showed ambiguous results of this improvement after CFTR modulator treatment. Elexacaftor/tezacaftor/ivacaftor medication improves pulmonary function and quality of life, whereas its effect on CPET has yet to be sufficiently demonstrated.
Methods: We performed a single group prospective observational study of 10 adolescent patients with cystic fibrosis who completed two CPET measurements between January 2019 and February 2023. During this period, elexacaftor/tezacaftor/ivacaftor treatment was initiated in all of them. The first CPET at the baseline was followed by controlled CPET at least one year after medication commencement. We focused on interpreting the data on their influence by the novel therapy. We hypothesized improvements in cardiorespiratory fitness following treatment. We applied the Wilcoxon signed-rank test. The data were adjusted for age at the time of CPET to eliminate bias of aging in adolescent patients.
Results: We observed significant improvement in peak workload, VO 2 peak , VO 2VT1 , VO 2VT2 , V E /VCO 2 slope, V E , V T , RQ, VO 2 /HR peak and RR peak. The mean change in VO peak was 5.7 mL/kg/min, or 15.9% of the reference value (SD ± 16.6; p= 0.014). VO 2VT1 improved by 15% of the reference value (SD ± 0.1; p= 0.014), VO 2VT2  improved by 0.5 (SD ± 0.4; p= 0.01). There were no differences in other parameters.
Conclusion: Exercise tolerance improved after elexacaftor/tezacaftor/ivacaftor treatment initiation. We suggest that the CFTR modulator alone is not enough for recovering physical decondition, but should be supplemented with physical activity and respiratory physiotherapy. Further studies are needed to examine the effect of CFTR modulators and physical therapy on cardiopulmonary exercise tolerance.