Real-world impact of Elexacaftor-Tezacaftor-Ivacaftor treatment in young people with Cystic Fibrosis: A longitudinal study

Abstract

Introduction: Elexacaftor, Tezacaftor, Ivacaftor (ETI) became available in the UK in August 2020 to treat people with Cystic Fibrosis (CF) aged > 12 years. We report a real-world study of clinical outcomes in young people treated with ETI at our CF centre within the first two years of its availability. Methods: Participants aged 12 to 17 were identified within our clinic, with demographic data supplemented by the UK CF registry. Comprehensive outcome data spanning two years pre and two years post-initiation of CFTR modulators were compiled from various local sources, including patient records, medication delivery logs, and clinical notes. Results: Of the 62 patients started on ETI (32 male, mean age 13.3 years), most (76%) were homozygous for the F508del mutation. Three discontinuations occurred: one pregnancy, two related to side effects. Adherence was high (Proportion of Days covered >90% both years). Following ETI initiation there was a significant increase in mean FEV1% (+11.7 units; 95% CI 7.4 - 15.6), sustained throughout the two-year treatment period. There was no association between baseline lung function and the degree of improvement or rate of decline post-treatment. Improvements were similar for all treatable genotypes. There was a small increase in BMI z-score at four months of treatment, returning to baseline by 24 months. There was a marked reduction in the need for intravenous antibiotics. Conclusions: ETI use in adolescents in a real-world setting led to sustained improvements in health outcomes, consistent with those seen in open trial extension studies