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 ₁ (ppFEV ₁ ) 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 ₁ 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 ₁ . In each age group, ppFEV ₁ 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.
Competing Interests: Declaration of Competing Interest All authors received nonfinancial assistance (assistance with manuscript preparation) from ArticulateScience LLC, which received funding from Vertex Pharmaceuticals Incorporated. Additional disclosures are as follows: GSS reports personal fees from Vertex; KVB and JB are employees of Vertex and may own stock or stock options in Vertex; EB is a former employee of Vertex and may own stock or stock options in the company; SJM is an employee of ICON Clinical Research, which received funding from various pharmaceutical, biotechnology, and device companies for providing clinical research services and received funding from Vertex for analytical services during the conduct of this study; MWK reports grants and personal fees from Vertex; PAF reports grants and personal fees from Vertex.
(Copyright © 2021. Published by Elsevier B.V.)