Effect of Aging on Deferasirox Therapy in Transfusion-dependent Patients. A Prospective- Retrospective, Cohort-study

Iron-chelation therapy is life-saving in patients on a chronic transfusion regimen as it reduces organ damage related to iron deposition in the tissues. Deferasirox, an iron-chelator, is characterized by pharmacokinetics variability, and some patients may discontinue the treatment due to toxicities.

Understanding whether deferasirox plasma levels are related to patients' specific characteristics could help to optimize DFX dosage.

We analyzed deferasirox plasma concentration in 57 transfusion-dependent anemic patients using the HPLC method in this prospective-retrospective cohort study. All outpatients (3 to 98 years) were treated with deferasirox (film-coated tablet) for at least one year (median dose, 16.5 mg/Kg once a day). Deferasirox plasma concentration was normalized for dose/Kg (C/dose) and corrected with a linear regression model that relates C/dose and the time of blood sampling (C^ref/dose).

No significant differences in C^ref/dose were found between males and females, either between different types of hemoglobinopathies or depending on the presence of the UGT1A1*28 polymorphism. C^ref/dose has a positive and significant correlation with age, creatinine, and direct bilirubin. C^ref/dose, instead, has a negative and significant correlation with Liver Iron Concentration (LIC), ferritin, and eGFR. C^ref/dose was significantly different between three age categories <18yrs, 18-50yrs, and >50yrs, with C^ref/dose median values of 1.0, 1.2, and 1.5, respectively.

The study evidenced that to ensure the efficacy of deferasirox in terms of control over LIC and, at the same time, a lesser influence on renal function, the dose of the drug to be administered to an elderly patient could be reduced.