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.