Effect of elexacaftor-tezacaftor-ivacaftor on pulmonary and endothelial function in a patient with advanced cystic fibrosis

Introduction. Cystic fibrosis (CF) is a genetic disorder of cystic fibrosis transmembrane conductance regulator (CFTR) resulting in production of thick mucus. The latest novelty in treatment of CF patients is triple combination of CFTR modulators (elexacaftor-tezacaftor-ivacaftor) that greatly improves CFTR function in epithelial cells leading to better pulmonary function. Objectives. CFTR is also located on endothelial cells and might be associated with endothelial dysfunction in CF. The aim of our single case study to explore the influence of CFTR modulators on endothelial function, which has yet to be investigated. Methods. Flow mediated dilation (FMD) is a well-established method for assessing endothelial function. FMD values below 4% are considered pathological. We evaluated FMD before and 1 month after introduction of elexacaftor-tezacaftor-ivacaftor in a 26-year-old female with advanced CF, who was among first patients in Slovenia to receive this treatment. Results. Patient’s condition quickly improved. She coughed up less mucus, her physical performance and pulmonary function improved (FEV1 increased from 26% to 38%), she no longer needed oxygen supplement during exercise and her need for pancreatic enzymes replacement therapy decreased. She reported no side effects. Before treatment her FMD value was dimished to 1.99%, one month after the initiation, the FMD value rose to 5.21%, reaching normal values for her age. Relative FMD improvement was as much as 261.8%. Conclusion. Endothelial function of our patient was severely impaired, as expected in CF. Its normalization was noted one month after initiation of the new treatment. The latter speaks in favour of the systemic effects of this drug, outside epithelial cells, specifically on endothelial cells.