Disease burden in people with cystic fibrosis heterozygous for F508del and a minimal function mutation.

Background: People with cystic fibrosis (CF) heterozygous for F508del-CFTR and a minimal function CFTR mutation (F/MF) that results in no CFTR protein or results in CFTR protein that is not responsive to tezacaftor, ivacaftor, and tezacaftor/ivacaftor in vitro comprise a sizeable percentage of the US CF population. This retrospective, cross-sectional, observational study aimed to characterize CF burden in this subpopulation.

Methods: People ≥2 years of age in the US CF Foundation Patient Registry with a CF diagnosis, F/MF genotype, and ≥1 encounters in 2017 were included. Descriptive analyses assessed lung function, nutritional parameters, microbiology, hospitalization and pulmonary exacerbation rates, and CF-related complications. Results were stratified by age group; select characteristics were summarized by percent predicted FEV (ppFEV) and ethnicity.

Results: 5348 people met inclusion criteria. Rates of positive bacterial cultures, pulmonary exacerbations, and hospitalizations were generally higher in older age groups. Prevalence of prescribed symptomatic CF therapies was substantial and also generally higher in older age groups. ppFEV was lower in older age groups. A greater percentage of adolescents and adults reported complications, including cirrhosis, osteoporosis, osteopenia, and sinus disease, than younger age groups. Increased prevalence of cultured Pseudomonas aeruginosa and prescribed chronic therapy was seen with decreasing ppFEV. In each age group, ppFEV was slightly higher in the non-Hispanic cohort than in the Hispanic cohort.

Conclusions: People with F/MF genotypes have substantial disease burden that worsened in older age groups consistent with the progressive nature of CF, indicating need for additional treatment options in this subpopulation.