Characteristics of individuals with cystic fibrosis in the United States ineligible for ivacaftor and elexacaftor/tezacaftor/ivacaftor.

BACKGROUND: We characterized people with cystic fibrosis (CF) ineligible by genotype (not age) for currently approved CFTR modulator therapy using data from the US CF Foundation Patient Registry (CFFPR).

METHODS: We summarized clinical characteristics using CFFPR data from 2017 to 2022. Annual rate of change in percent predicted of forced expiratory volume in one second (ppFEV1) was estimated using generalized estimating equations.

RESULTS: A total of 2,790 individuals with CF met inclusion criteria. In 2022, 12 % were less than 6 years old, 16 % were age 6-12 years, 18 % age 12-18 years and 54 % were ≥18 years. The proportion identified as White was 74 %, 17 % Black, and 26 % as Hispanic. The median (IQR) age at diagnosis was 1.2 (0.5, 9.1) months for children and 3.1 (0.3, 17.4) years for adults. Median (IQR) ppFEV1 among children was 91.9 (80.3; 102.4) and among adults, 74.3 (52.4; 90.4). Pancreatic enzymes were prescribed for 77.8 %. Population-level average (95 % CI) rates of decline in ppFEV1 among the pancreatic insufficient population was -1.5 per year (-1.8; -1.2) for ages 6 to <11 years, -2.2 per year (-2.6; -1.8) for ages 12 to <18 years, and -1.5 per year (-1.7; -1.3) for adults.

CONCLUSIONS: We describe the CFTR modulator ineligible population in the US in 2017-2022. With a growing pipeline of therapies aimed at improving CFTR function for those who cannot benefit from modulators due to ineligibility, characterization of both the size and outcomes of these populations are critical to inform optimal clinical development plans and future clinical trials.