Abstract:
The 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 Exjade®. 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 ≥7 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 ≥7 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 ± 2.4 mg Fe-g dw, -57 ng-mL; P = not significant) and significantly decreased in the high-iron cohort (-6.1 ± 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 ≥7 mg Fe-g dw cohort (39.4 versus 20.8 percent; 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. © 2012 The Author(s).