Change in the 6-min walk test among 71 patients with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor.

BACKGROUND

Elexacaftor/tezacaftor/ivacaftor (ETI) has led to substantial improvements in the clinical outcome of people with cystic fibrosis (pwCF). However, its effects on exercise capacity remain uncertain.

METHODS

This retrospective cohort study included 71 pwCF who started ETI between March 2020 and September 2022. The best performance on the 6-min walk test (6MWT), defined as the peak walking distance achieved, was compared between the 12 months preceding ETI initiation and the first 14 months of treatment. Pulmonary function tests (PFT) and Cystic Fibrosis Questionnaire-Revised (CFQ-R) were analyzed at treatment initiation and after 12 months.

RESULTS

After starting ETI, the 6MWT was performed at a median interval of 356 [296-380] days. The mean 6-min walk distance (6MWD) was 641 m ± 85.5 at baseline. After treatment, the 6MWD showed a significant absolute increase of 15.8 m (P = 0.007). Improvement was greater in pwCF with a percent predicted FEV1 (ppFEV1) ≤40, showing a mean increase of 37.8 m (P = 0.009), and in those without prior CFTR modulator therapy with an increase of 21.6 m (P = 0.016). After 12 months, the absolute increase in ppFEV1 was 15.8 (P < 0.001). The absolute changes from baseline in CFQ-R physical and respiratory scores were 17.9 (P < 0.001) and 27 points (P < 0.001), respectively. No correlation was found between changes in 6MWT and changes in PFT results.

CONCLUSIONS

ETI improved exercise capacity in pwCF, as evidenced by a significant increase in the 6MWD. ETI was also associated with improvements in physical-related quality of life. Changes in PFT results cannot predict changes in 6MWT results after ETI therapy.