OBJECTIVES

CF is a rare, multi-systemic genetic disease characterized by impaired survival and reduced health-related quality-of-life (HRQoL). The CFQ-R-8D (Acaster NACFC 2019) is a disease-specific preference-based scoring algorithm that estimates utilities based on a standard, well-validated HRQoL instrument in CF (CFQ-R). The CFTR modulator ELX/TEZ/IVA provided substantial improvements in lung function (measured by ppFEV₁) and CFQ-R respiratory symptom domains in a registrational trial enrolling people with CF (pwCF) aged ≥12 years with F508del/minimal function (F/MF) genotypes (NCT03525444). Here we applied the CFQ-R-8D to estimate utility benefit in pwCF not previously eligible for CFTR modulators treated with ELX/TEZ/IVA, including benefit beyond that explained by lung function.

METHODS

The CFQ-R-8D algorithm was used to calculate health-state utilities from CFQ-R data collected in participants aged ≥14 years in NCT03525444, a 24-week, placebo-controlled study. A mixed effects model for repeated measures (MMRM) was used to estimate the utility benefit of ELX/TEZ/IVA in pwCF using CFQ-R-8D data from Week 4 and beyond. Utility benefit was estimated with and without controlling for ppFEV₁, measured at time of CFQ-R-8D assessment (categorical variable: ≥70% vs <70%).

RESULTS

Average CFQ-R-8D utility at baseline was 0.81 (on a 0.00 to 1.00 scale) in both ELX/TEZ/IVA and placebo cohorts. By Week 4, average utility increased 0.07 among pwCF receiving ELX/TEZ/IVA and decreased 0.01 among those receiving placebo. Without adjusting for ppFEV₁, ELX/TEZ/IVA provided an estimated utility benefit of 0.083 (p<0.001) versus placebo measured across Weeks 4 to 24. Controlling for ppFEV₁, the estimated utility benefit was 0.079 (p<0.001).

CONCLUSIONS

Meaningful utility improvements in pwCF with F/MF genotypes were achieved by Week 4 after initiating ELX/TEZ/IVA and are consistent with improvements observed over the subsequent 20 weeks of treatment. Utility benefit was demonstrated even after controlling for ppFEV₁, suggesting ELX/TEZ/IVA confers substantial HRQoL benefits beyond those mediated by improvement in ppFEV₁.