Effects of Elexacaftor/Tezacaftor/Ivacaftor on cough frequency, physical activity patterns, and sleep quality in adolescents and adults with cystic fibrosis

Background

Cystic fibrosis (CF) transmembrane conductance regulator modulators improve lung function, however, effects on cough frequency, physical activity, and sleep have not been assessed in clinical studies.

Methods

After a 12-week, phase 4 pilot feasibility study, we conducted a 13-week, phase 3b, open-label study in participants with CF aged ≥12 years previously naïve to elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) to assess the effects of ELX/TEZ/IVA on cough frequency, physical activity, and sleep using wearable cough monitors and actigraphy sensors (VX-445–126).

Results

In study VX-445–126 (N = 81), participants treated with ELX/TEZ/IVA experienced a 91.7% reduction in cough frequency (cough events per day) (95% CI, 89.2% to 93.6%; 241.3 coughs per day at baseline to 20.3 coughs per day) from baseline at the average of week 8 through week 12 (primary endpoint). Total steps per day (secondary endpoint) increased by 638 (95% CI, 298 to 977) at the average of week 8 through week 12. Time spent above sedentary physical activity per day, time spent on moderate-to-vigorous physical activity per day, and total mean activity count per day all increased from baseline at the average of week 8 through week 12 (other efficacy endpoints). While no changes in sleep activity patterns were observed in actigraphy data, patient-reported measures of sleep quality improved (other efficacy endpoints). ELX/TEZ/IVA was generally safe and well-tolerated.

Conclusions

ELX/TEZ/IVA treatment led to a > 90% reduction in daily cough frequency, with sustained improvements in physical activity and better perceptions of sleep quality.