Assessment of Physical Condition in Cystic Fibrosis Patients during 12-month Treatment with Cystic Fibrosis Transmembrane Conductance Regulator Modulators

Abstract

Objective − To investigate the effect of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy on physical condition in children with cystic fibrosis (CF) during a 12month period.

Materials and Methods − This is a retrospective cohort study including children aged ≥5 years treated with Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) or Lumacaftor/ Ivacaftor (LUM/IVA). A six-minute walk test (6MWT) was performed at baseline and at the 3-month follow-ups. Changes in spirometry and sweat chlorides, and body mass index (BMI) were also observed. Collected data were analysed for changes in 6MWT results in correlation with other parameters. The 6MWT results were compared to those predicted for healthy peers. Missing values were replaced using imputation.

Results − Study includes 34 patients (median age 14 years); 28 received ELX/TEZ/ IVA, and 6 LUM/IVA. The average 6MWT walking distance (6MWD) increased from 519.3±107.7 m at baseline to 620.0±99.5 m after 12 months (P<0.0001). The 12 month 6MWD values matched those expected for healthy peers. The increase in BMI z-score (P=0.019) and ppFEV1 (P<0.0001) visible at the 3-month followup was sustained throughout the rest of the year. Sweat chloride concentration decreased (P< 0.0001); after 12 months 13/34 subjects had values below 60 mmol/L. No correlation between 6MWD and other parameters was observed.

Conclusion − Significant improvement in 6MWT results was already visible at three months following the initiation of CFTR modulator treatment. After 12 months patients performed 6MWT at a level indistinguishable from that expected of healthy peers.