S65 Impact of elexacaftor/tezacaftor/ivacaftor triple combination therapy on health-related quality of life in people with cystic fibrosis heterozygous for F508del and a minimal function mutation (F/MF): 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, placebo-controlled study (NCT03525444) in people with cystic fibrosis aged ≥12 years with F/MF genotypes; people with cystic fibrosis were randomised 1:1 to receive ELX/TEZ/IVA or placebo for 24 weeks. 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 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 placebo. Although a minimal clinically important difference has not been determined for non-respiratory domain scores, score increases signify improvement. Results 403 people with cystic fibrosis were randomised and dosed in the study. Improvements with ELX/TEZ/IVA over placebo were observed in all non-respiratory domain scores except digestion (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/MF genotypes, illustrating broad benefits of treatment beyond previously reported respiratory and other clinical improvements. Please refer to page A239 for declarations of interest related to this abstract.