Università di Milano, Policlinico Foundation IRCCS, Milan, Italy.
Haematologica. 2010 Apr;95(4):557-66. doi: 10.3324/haematol.2009.014696. Epub 2009 Nov 30.
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 >or=2 years) with transfusional hemosiderosis from various types of anemia.
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.
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 therapy 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).
在对去铁酮（Exjade）进行临床评估后得出结论，在选择剂量时，除了基线体内铁负荷外，还应考虑正在进行的输血铁摄入。EPIC 研究是有史以来针对铁螯合剂进行的最大规模研究，首次评估了基于输血铁摄入的固定起始剂量去铁酮（根据输血铁摄入，推荐剂量为 20mg/kg/日用于每月接受 2-4 单位浓缩红细胞的患者，10 或 30mg/kg/日用于分别接受较少或更频繁输血的患者），并通过血清铁蛋白趋势和安全性标志物指导剂量滴定，是否能为各种类型贫血所致输血性血色素沉着症患者提供临床可接受的螯合作用。
建议的初始剂量为每月接受 2-4 单位浓缩红细胞的患者为 20mg/kg/日，接受更频繁输血的患者为 10 或 30mg/kg/日。剂量调整基于 3 个月的血清铁蛋白趋势和对安全性标志物的持续评估。主要疗效终点为与基线相比，52 周时血清铁蛋白的变化。
共纳入 1744 例患者，包括地中海贫血（n=1115）、骨髓增生异常综合征（n=341）、再生障碍性贫血（n=116）、镰状细胞病（n=80）、罕见性贫血（n=43）和其他输血性贫血（n=49）。总体而言，血清铁蛋白较基线显著降低（-264ng/mL；P<0.0001），反映了剂量调整和持续的铁摄入。最常见（>5%）的不良事件为胃肠道紊乱（28%）和皮疹（10%）。结论：对该大型前瞻性数据的分析证实了各种贫血患者对螯合治疗的反应，支持基于输血铁摄入的初始去铁酮剂量，随后根据血清铁蛋白和安全性标志物的趋势进行剂量滴定（临床试验注册号：NCT00171821）。
