Real-world efficacy, safety and heterogenicity of efficacy of elexacaftor-tezacaftor-ivacaftor in younger children (6-11 years old) with cystic fibrosis.

BACKGROUND: Heterogenicity of efficacy of elexacaftor-tezacaftor-ivacaftor (ETI) therapy in the real world in younger children (6-11 years old) is not known.

METHODS: This is a longitudinal observational study. Clinical data at baseline and at one-year of therapy were compared for the total cohort and for following subgroups: genotype (homozygous vs. heterozygous for F508del), severity of lung disease at ETI initiation (ppFEV1 <80 vs. ≥80) and naïve vs. previously exposed to cystic fibrosis transmembrane conductance regulator (CFTR) modulators.

RESULTS: Among the total cohort of 70 chCF (children with cystic fibrosis), median (interquartile range) age was 9.0 (6.4, 10.0) years, 40 (57%) were homozygous for F508del, 52 (80%) had ppFEV1 ≥80 at baseline and 31 (44%) were naive to previous CFTR modulator therapies. Significant increases in mean ppFEV1 (+4.8%, p = 0.002) and mean body mass index (BMI) (+0.68 kg/m2, p < 0.001) were observed at one year of ETI therapy, limited to homozygous and naïve subgroups and those with lower ppFEV1 at baseline. After one-year on ETI therapy, significant improvements were noted in pulmonary exacerbations, hospital admissions, antibiotic courses, number of chCF receiving daily chest therapy, dornase alfa and hypertonic saline (p < 0.05 for all) in total cohort and in most of the subgroups- CONCLUSION: ETI therapy was associated with improved clinical outcomes in younger children, and heterogenicity was noted in effectiveness.