Real-world outcomes after initiation of Elexacaftor/tezacaftor/ivacaftor in an adolescent cohort with cystic fibrosis.

Background: This study assessed the real-world clinical outcomes and adherence to Elexacaftor/tezacaftor/ivacaftor (ETI) in adolescents with cystic fibrosis (CF).

Methods: A retrospective cohort study was conducted in patients aged 12 to 18 years at a tertiary pediatric hospital in Adelaide, Australia. Demographic data include age, CF genotype, and prior use of modulator therapy. Primary outcome measures were percent predicted FEV1 (ppFEV1), body mass index (BMI), and BMI-for-age (BMI z-score). Secondary outcome measures included hospital admissions for pulmonary exacerbations, CF pathogens in sputum, elevated transaminase levels, and medication adherence (MPR) for ETI and dornase alfa.

Results: 42 patients (median age 15.29 years) were assessed over 12 months of ETI therapy. ppFEV1 increased by 4.1% (95% CI: 1.2, 7.0; p<0.001) in the cohort, with improvements in both homozygous (3.6%) and heterozygous (4.9%) subgroups. BMI increased by 1.0 kg/m² (95% CI: 0.5, 1.5; p<0.001), but no significant change in BMI z-score was observed (mean change 0.0, 95% CI -0.1,0.2). There was a 60% reduction in pulmonary exacerbations requiring hospital admission (rate ratio 0.4; p<0.001) and a 40% reduction in CF pathogens (rate ratio 0.6; p=0.004). Adherence (MPR) was 92.2% for ETI and 13.2% for dornase alfa.

Conclusions: This study demonstrated modest improvement in ppFEV1 and BMI compared to previous large studies. There was a decrease in pulmonary exacerbations and number of CF pathogens. ETI adherence was high, while dornase alfa adherence was low. These results highlight the importance of further real-world studies in CF, including methods of measuring and improving adherence to therapies.