Real Life Evaluation of the Multi-organ Effects of Lumacaftor/Ivacaftor on F508del Homozygous Cystic Fibrosis Patients

Background: Lumacaftor/Ivacaftor (LUM-IVA), a cystic fibrosis transmembrane conductance regulator (CFTR) protein corrector-potentiator combination, improves lung function and reduces pulmonary exacerbations (PEx) in F508del homozygous CF patients. However, the systemic effects of LUM-IVA outside the respiratory and nutritional domains have not yet been thoroughly investigated. Methods: A prospective, real-world, one-year study was performed on F508del homozygous adult CF patients who commenced treatment with LUM-IVA. Pancreatic function, bone metabolism, fertility status, nutritional and pulmonary factors were evaluated. Results: 12 patients with a mean age of 28.3 years (18.6-43.9) were recruited. Following 12 months of treatment, no changes were detected in glucose, insulin, c-peptide or BMI values. A significant relative decrease in mean alkaline-phosphatase levels (122.8 U/L vs 108, p=0.008) and a trend toward an increase in calcium levels (9.5 vs 9.8 mg/dL, p=0.0681) were observed. A non-significant improvement in mean DEXA spine t-score after a year of treatment (-2.1 vs -1.6, n=4, p=0.12) was detected. Sweat chloride concentrations decreased significantly after treatment (-21.4 mEq/L; p=0.003). Pulmonary outcome evaluations revealed improvement in spirometry values during the first three months (FEV1 by 5.7% p=0.019, FEF25-75 by 4.3% p=0.035) with no change in chest CT Bhalla score and CFQR after one year. There was also a shift from IV to oral antibiotics for PEx treatment. Conclusions: After a year of treatment, a stabilization was observed in the pancreatic indices, nutritional status, structure and function of the lungs, with a beneficial effect on bone mineral metabolism and CFTR function. Additional studies should investigate the effect of CFTR modulators on extra-pulmonary manifestations.The ClinicalTrials.gov registration number of the study is NCT04623879, registered on 10/11/2020, “retrospectively registered”.