Improvements in health-related quality of life in people with cystic fibrosis ≥6 years of age treated with vanzacaftor/tezacaftor/deutivacaftor

Abstract

Background Vanzacaftor/tezacaftor/deutivacaftor (VNZ/TEZ/D-IVA) was shown to provide greater restoration of cystic fibrosis transmembrane conductance regulator (CFTR) function than prior CFTR modulators in people with cystic fibrosis (CF) aged ≥6 years. Here, we assessed the impact of VNZ/TEZ/D-IVA on health-related quality of life (HRQoL) in children, adolescents, and adults with CF. Methods Post-hoc analyses were conducted using VNZ/TEZ/D-IVA Phase 3 studies in adolescents and adults with F508del /minimal function variant ( F /MF) genotypes (SKYLINE 102) or F/F and other responsive genotypes (SKYLINE 103) and children aged 6–11 years across all responsive genotypes (RIDGELINE 105). For participants aged ≥14 years, CF Questionnaire-Revised-8 Dimensions (CFQ-R-8D) utility scores, a CF-specific, preference-based scoring algorithm based on CFQ-R data, were compared for VNZ/TEZ/D-IVA and ELX/TEZ/IVA treatment through Week 52. For children aged 6–11 years, absolute changes in CFQ-R non-respiratory domain (CFQ-R non-RD) scores from baseline, following an ELX/TEZ/IVA run-in period, were assessed through Week 24. Results CFQ-R-8D utility scores were higher in adolescents and adults given VNZ/TEZ/D-IVA compared to ELX/TEZ/IVA (pooled 0.017; nominal P = 0.01); participants with F /MF genotypes had larger changes (0.031; nominal P = 0.004) compared to non- F /MF genotypes (0.008; nominal P = 0.35). Children treated with VNZ/TEZ/D-IVA had improvements in 6 out of 7 CFQ-R non-RD scores, ranging from 3.7 [95 % CI: 1.0, 6.3] points in emotional functioning to 7.2 [95 % CI: 3.8, 10.5] points in social functioning. Conclusions VNZ/TEZ/D-IVA was associated with higher HRQoL in adolescents and adults aged ≥14 years compared to ELX/TEZ/IVA, with largest changes in participants with F /MF genotypes, and in children aged 6–11 years compared to ELX/TEZ/IVA baseline. These results highlight potential HRQoL benefits from greater CFTR function restoration with VNZ/TEZ/D-IVA.