Effect of Aging on Deferasirox Therapy in Transfusion-dependent Patients. A prospective-retrospective, cohort-study

Valeria Marini; Valeria Maria Pinto; Manuela Stella; Carmen Fucile; Francesca Lantieri; Giacomo Luci; Barbara Gianesin; Lorenzo Bacigalupo; Gian Luca Forni; Francesca Mattioli

doi:10.2174/1389200224666221209144420

Effect of Aging on Deferasirox Therapy in Transfusion-dependent Patients. A prospective-retrospective, cohort-study

Curr Drug Metab. 2022 Dec 9. doi: 10.2174/1389200224666221209144420. Online ahead of print.

Authors

Valeria Marini^{1

2}, Valeria Maria Pinto³, Manuela Stella^{1

2}, Carmen Fucile⁴, Francesca Lantieri⁵, Giacomo Luci⁴, Barbara Gianesin^{3

6}, Lorenzo Bacigalupo⁷, Gian Luca Forni³, Francesca Mattioli^{1

2}

Affiliations

¹ Clinical Pharmacology Unit, EO Ospedali Galliera, Mura delle Cappuccine, n. 14. I-16128 Genoa, Italy.
² Department of Internal Medicine, Clinical Pharmacology and Toxicology Unit, University of Genoa, Viale Benedetto XV, n. 2. I-16132 Genoa, Italy.
³ Centro della Microcitemia, Anemie Congenite e Dismetabolismo del Ferro, EO Ospedali Galliera, Mura delle Cappuccine, n. 14. I-16128 Genoa, Italy.
⁴ Department of Clinical and Experimental Medicine, University of Pisa, Via Savi, n.10. I-56126 Pisa, Italy.
⁵ Health Science Department, Biostatistics Unit, University of Genoa, Via Pastore, n. 1. I-16132 Genoa, Italy.
⁶ ForAnemia Foundation, Via Garibaldi, n. 7. I-16124 Genoa, Italy.
⁷ Department of Diagnostic Imaging, Radiology and Nuclear Medicine, EO Ospedali Galliera, Mura delle Cappuccine, n. 14. I-16128 Genoa, Italy.

PMID: 36503397
DOI: 10.2174/1389200224666221209144420

Abstract

Background: 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.

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

Methods: 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 (Cref/dose).

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

Conclusion: 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.

Keywords: Aging; Deferasirox; Iron chelation; Physiologically-based pharmacokinetics; Therapeutic drug monitoring.; Tolerability; Transfusion-dependent patients.