Efficacy and safety of deferasirox at low and high iron burdens: results from the EPIC magnetic resonance imaging substudy

WOS: 000313445100009PubMed ID: 23086508The effect of deferasirox dosing tailored for iron burden and iron loading based on liver iron concentration (LIC) was assessed over 1 year in less versus more heavily iron-overloaded patients in a substudy of the Evaluation of Patients' Iron Chelation with ExjadeA (R). Deferasirox starting dose was 10-30 mg/kg/day, depending on blood transfusion frequency, with recommended dose adjustments every 3 months. Therapeutic goals were LIC maintenance or reduction in patients with baseline LIC < 7 or a parts per thousand yen7 mg Fe/g dry weight (dw), respectively. Changes in LIC (R2-magnetic resonance imaging) and serum ferritin after 1 year were assessed. Adverse events (AEs) and laboratory parameters were monitored throughout. Of 374 patients, 71 and 303 had baseline LIC < 7 and a parts per thousand yen7 mg Fe/g dw, respectively; mean deferasirox doses were 20.7 and 27.1 mg/kg/day (overall average time to dose increase, 24 weeks). At 1 year, mean LIC and median serum ferritin levels were maintained in the low-iron cohort (-0.02 A +/- 2.4 mg Fe/g dw, -57 ng/mL; P = not significant) and significantly decreased in the high-iron cohort (-6.1 A +/- 9.1 mg Fe/g dw, -830 ng/mL; P < 0.0001). Drug-related gastrointestinal AEs, mostly mild to moderate, were more frequently reported in the < 7 versus a parts per thousand yen7 mg Fe/g dw cohort (39.4 versus 20.8 %; P = 0.001) and were not confounded by diagnosis, dosing, ethnicity, or hepatitis B and/or C history. Reported serum creatinine increases did not increase in low- versus high-iron cohort patients. Deferasirox doses of 20 mg/kg/day maintained LIC < 7 mg Fe/g dw and doses of 30 mg/kg/day were required for net iron reduction in the high-iron cohort, with clinically manageable safety profiles. The higher incidence of gastrointestinal AEs at lower iron burdens requires further investigation.Novartis Pharma AG; Novartis Pharmaceuticals; FerroKin BioSciences Inc.This study was sponsored by Novartis Pharma AG. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. We thank Rebecca Helson for the medical editorial assistance with this manuscript.; JBP reports participation in advisory boards for Novartis Pharmaceuticals. ATT reports receiving research funding and honoraria from Novartis Pharmaceuticals. YA reports receiving research grant support, consulting fees, and lecture fees from Novartis Pharmaceuticals and research grant support from FerroKin BioSciences Inc. PS reports receiving research funding from Novartis Pharmaceuticals. MSE, AE-B, S-HL, and LLC declare that they have no conflicts of interest to disclose. DH is a full-time employee of Novartis Pharmaceuticals. NM is a full-time employee of Novartis Pharma AG