Tailoring iron chelation by iron intake and serum ferritin: The prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias
Journal
Haematologica
Journal Volume
95
Journal Issue
4
Pages
557-566
Date Issued
2010
Author(s)
Abstract
Background: Following a clinical evaluation of deferasirox (Exjade?) it was concluded that, in addition to baseline body iron burden, ongoing transfusional iron intake should be considered when selecting doses. The 1-year EPIC study, the largest ever investigation conducted for an iron chelator, is the first to evaluate whether fixed starting doses of deferasirox, based on transfusional iron intake, with dose titration guided by serum ferritin trends and safety markers, provides clinically acceptable chelation in patients (aged ?2 years) with transfusional hemosiderosis from various types of anemia. Design and Methods: The recommended initial dose was 20 mg/kg/day for patients receiving 2-4 packed red blood cell units/month and 10 or 30 mg/kg/day was recommended for patients receiving less or more frequent transfusions, respectively. Dose adjustments were based on 3-month serum ferritin trends and continuous assessment of safety markers. The primary efficacy end-point was change in serum ferritin after 52 weeks compared with baseline. Results: The 1744 patients enrolled had the following conditions; thalassemia (n=1115), myelodysplastic syndromes (n=341), aplastic anemia (n=116), sickle cell disease (n=80), rare anemias (n=43) and other transfused anemias (n=49). Overall, there was a significant reduction in serum ferritin from baseline (-264 ng/mL; P<0.0001), reflecting dosage adjustments and ongoing iron intake. The most common (>5%) adverse events were gastrointestinal disturbances (28%) and skin rash (10%). Conclusions: Analysis of this large, prospectively collected data set confirms the response to chelation ther- apy across various anemias, supporting initial deferasirox doses based on transfusional iron intake, with subsequent dose titration guided by trends in serum ferritin and safety markers (clinicaltrials.gov identifier: NCT00171821). ? 2010 Ferrata Storti Foundation.
Subjects
Iron chelation therapy; Transfusion medicine; Transfusion-dependent anemias
SDGs
Other Subjects
alanine aminotransferase; deferasirox; deferiprone; ferritin; iron; abdominal pain; abnormal laboratory result; acute kidney failure; adolescent; adult; aged; alanine aminotransferase blood level; anemia; aplastic anemia; arthralgia; article; cataract; child; clinical trial; controlled clinical trial; controlled study; diarrhea; drug dose increase; drug dose reduction; drug dose titration; drug efficacy; drug eruption; drug response; drug safety; drug withdrawal; erythrocyte transfusion; female; ferritin blood level; gastrointestinal symptom; hemosiderosis; human; iron chelation; iron intake; major clinical study; male; multicenter study; myelodysplastic syndrome; nausea; outcome assessment; phase 3 clinical trial; proteinuria; recommended drug dose; sickle cell anemia; side effect; thalassemia; treatment duration; upper abdominal pain; vomiting; Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Benzoic Acids; Blood Transfusion; Child; Child, Preschool; Female; Ferritins; Humans; Iron Chelating Agents; Iron Overload; Iron, Dietary; Male; Middle Aged; Prospective Studies; Thalassemia; Tissue Distribution; Triazoles; Young Adult
Type
journal article