One year effect of tezacaftor and ivacaftor on functional exercise capacity and muscle strength in people with cystic fibrosis

Abstract

Background: The 1-min sit-to-stand test (1STST) is a practical tool to evaluate physical capacity. The aim of this study was to assess the impact of tezacaftor and ivacaftor on functional exercise capacity, muscle strength and symptoms in people with cystic fibrosis (PwCF).

Methods: The assessments were performed during the first year of tezacaftor and ivacaftor using the 1STST, 6-min walk test (6MWT), MicroFET2 dynamometer®, CF Questionnaire-Revised (CFQ-R), Leicester Cough Questionnaire (LCQ). Forced expiratory volume in 1 s (FEV1), body mass index (BMI), pancreatic sufficiency status, genotype and microbiologic data were also collected.

Results: Fifty-four PwCF participated to the study and took at least one dose of tezacaftor-ivacaftor. Mean age was 26y±10 (±SD), median BMI 20.9 kg/m² (interquartile range) (19.4; 23.5) and mean FEV1 82 percent of predicted values (%PV) ± 21. Significant correlations were found at baseline between the 1STST and the 6MWT (r = 0.617, p < 0.0001), the quadriceps strength (r = 0.6556, p < 0.0001) and the FEV1 (r = 0.29, p = 0.03). After one year of treatment, the 1STST increased significantly in terms of number of repetitions (n) (median 50 versus 58.5, p < 0.0001), %PV (101.1 versus 115.2%PV, p = 0.0003) and n times weight in kg (2885 versus 3389nxkg, p < 0.0001). The 6MWT distance and quadriceps strength were not modified after treatment but during the 6MWT, oxygen desaturation decreased significantly. FEV1, BMI, CFQ-R, LCQ improved as previously demonstrated.

Conclusion: After one year of tezacaftor and ivacaftor, the 1STST improves, suggesting that the 1STST seems more responsive than the 6MWT and the MicroFET2 dynamometer® to assess the effects of CFTR modulators.

Keywords: CFTR modulators; Cystic fibrosis; Functional exercise capacity; One-minute sit-to-stand test; Quadriceps strength.

Fig. 1

Correlations at baseline between 1STST and lung function n = 51, Spearman correlation and simple linear regression (A), 6MWT distance n = 49, Pearson correlation and simple linear regression (B) and MVCQ n = 49, Pearson correlation and simple linear regression (C). FEV1, forced expiratory volume in 1 s; PV, predicted values; 1STST, the 1-min sit-to-stand test; nxkg, number of repetitions as a product of bodyweight expressed in kilogram; 6MWT, 6-min walk test; m, meter; MVCQ, maximal isometric voluntary contraction of the quadriceps; N-m, Newton-meter.

Fig. 2

1STST before and after 12 months of tezacaftor and ivacaftor expressed in number of repetitions n = 51 and 46, Wilcoxon test (A), % predicted values n = 48 and 42, paired t-test (B) and nxkg n = 51 and 46, paired t-test (C). 6MWT oxygen desaturation in people with CF having oxygen desaturation during the test n = 28 and 28, Wilcoxon test (D). 1STST, 1-min sit-to-stand test; nxkg, number of repetitions as a product of bodyweight expressed in kilogram; 6MWT, 6-min walk test.

Fig. 3

Evolution of 1STST expressed in number of repetitions n = 51, n = 51, n = 47, n = 40, n = 46 (A), FEV1 n = 54, n = 53, n = 50, n = 45 and n = 50 (B) and BMI n = 54, n = 53, n = 51, n = 46 and n = 50 (B) after 1, 4, 7 and 12 months of treatment. 1STST, the 1-min sit-to-stand test; FEV1, forced expiratory volume in 1 s; PV, predicted values; BMI, body mass index; kg/m², kilogram divided by the square meter. Mixed-effects model, **p < 0.01, ***p < 0.001, ****p < 0.0001 compared to baseline.

Fig. 4

Effects of one year of tezacaftor and ivacaftor on FEV1 n = 54 and n = 50 (A), BMI n = 54 and n = 50 (B), CFQ-R n = 49 and n = 47 (C), LCQ n = 52 and n = 49 (D), intravenous antibiotherapy days the year before and after tezacaftor and ivacaftor n = 54 and n = 54 (E). FEV1, forced expiratory volume in 1 s; PV, predicted values; BMI, body mass index; kg/m², kilogram divided by the square meter; CFQ-R, cystic fibrosis questionnaire-revised; LCQ, Leicester cough questionnaire; IV, intravenous. Wilcoxon test.