IMPACT OF ELEXACAFTOR/TEZACAFTOR/yIVACAFTOR TRIPLE COMBINATION THERAPY ON HEALTH-RELATED QUALITY OF LIFE IN PEOPLE WITH CYSTIC FIBROSIS HOMOZYGOUS FOR F508DEL: RESULTS FROM A PHASE 3 CLINICAL STUDY

Introduction and Objectives Efficacy and safety of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), a novel CFTR modulator therapy, were evaluated in a Phase 3, randomised, double-blind, active-control study (NCT03525548) in people with cystic fibrosis aged ≥12 years with F/F genotypes; people with cystic fibrosis were randomised 1:1 to receive ELX/TEZ/IVA or TEZ/IVA for 4 weeks, after a 4-week TEZ/IVA run-in. Primary and secondary outcomes, including marked improvement in clinical outcomes and Cystic Fibrosis Questionnaire–Revised (CFQ-R) respiratory domain scores, were reported previously. The aim of this analysis is to report the effects of ELX/TEZ/IVA vs TEZ/IVA on 11 other CFQ-R domains. Methods The CFQ-R, a validated health-related quality of life instrument, was administered at study visits in the Phase 3 trial. Absolute change from baseline in CFQ-R respiratory domain score was a prespecified secondary endpoint; other domains were prespecified other endpoints. A mixed-effects model for repeated measures was used to calculate the change from baseline in CFQ-R domain scores vs TEZ/IVA. Minimal clinically important differences have not been determined for non-respiratory domains; score increases signify improvement. Results 107 people with cystic fibrosis were randomised and dosed in the treatment period. Improvements with ELX/TEZ/IVA over TEZ/IVA were seen in 7 of the 11 non-respiratory domain scores (Table), including vitality, physical functioning and health perceptions. Conclusions ELX/TEZ/IVA improved multiple aspects of health-related quality of life in people with cystic fibrosis with F/F genotypes over TEZ/IVA, illustrating broad benefits of treatment beyond previously reported clinical improvements. Please refer to page A239 for declarations of interest related to this abstract.