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 %; 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.
Highlights
R2-magnetic resonance imaging (R2-MRI) methodologyPatients with conditions resulting in iron overload, where their liver iron concentration (LIC) exceeds 7 mg Fe/g dry weight, are at an increased risk of progressive organ dysfunction and/or early death due to iron-related complications [1,2,3,4,5,6,7,8]
When determining whether ethnicity influenced the incidence of gastrointestinal Adverse events (AEs), the analysis showed that non-Oriental patients had a higher risk of gastrointestinal AEs, which was not confounded by diagnosis, baseline LIC category, or history of hepatitis B and/or C
With widening therapeutic and investigative/monitoring options in iron chelation therapy, an emerging theme includes the benefits and safety of achieving target LIC
Summary
R2-MRI methodologyPatients with conditions resulting in iron overload, where their liver iron concentration (LIC) exceeds 7 mg Fe/g dry weight (dw), are at an increased risk of progressive organ dysfunction and/or early death due to iron-related complications [1,2,3,4,5,6,7,8]. The international, multicenter Evaluation of Patients’ Iron Chelation with Exjade® (EPIC) study was the first to prospectively demonstrate that effective chelation can be achieved using fixed starting doses of deferasirox based on ongoing iron intake from blood transfusions, with subsequent dose titration guided by serum ferritin levels and safety markers [11]. Deferasirox efficacy in EPIC was primarily monitored using serum ferritin, a large subset of patients was assessed by noninvasive LIC measurement using R2-magnetic resonance imaging (R2-MRI). In this subset of patients, the efficacy and safety of deferasirox in patients with lower and higher iron burdens were, assessed. This predefined analysis evaluates deferasirox for maintaining LIC in patients with baseline LIC
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