Cases Aleix
Nephrology Unit, Hospital Clinic, Barcelona, Spain.
Drugs Today (Barc). 2003 Jul;39(7):477-95. doi: 10.1358/dot.2003.39.7.799441.
Darbepoetin alfa is a novel erythropoiesis-stimulating protein developed for the treatment of anemia. It is a hyperglycosylated analog of recombinant human erythropoietin with the same mechanism of action as erythropoietin, but with a three-fold longer terminal half-life after intravenous administration than recombinant human erythropoietin and the native hormone both in animal models and in humans. Clinical studies in patients with chronic renal failure either receiving or not receiving dialysis have shown that darbepoetin alfa is equivalent to recombinant human erythropoietin in terms of increases in hemoglobin concentration, percentage of patients achieving target hemoglobin concentration and average time to reach target hemoglobin concentration, although darbepoetin alfa is administered less frequently (once weekly or every other week). Clinical trials in cancer patients either receiving or not receiving chemotherapy have demonstrated that darbepoetin alfa is safe and effective in alleviating anemia at dose intervals of once every 1, 2 or 3 weeks, and results suggest that it may achieve greater and more rapid responses than recombinant human erythropoietin in cancer patients. Furthermore, an improvement in health-related quality of life has been observed in association with anemia correction using darbepoetin alfa therapy in these patients. Darbepoetin alfa has been approved for intravenous and subcutaneous administration by the European Commission and the FDA for the treatment of anemia in patients with chronic renal failure. Additionally, this product was recently approved by the FDA for the treatment of anemia in patients with nonmyeloid malignancies where anemia is due to the effect of concomitantly administered chemotherapy. The recommended starting dose in chronic renal failure patients is 0.45 microg/kg once weekly for both intravenous and subcutaneous administration, with subsequent titration based on the hemoglobin concentration. In cancer patients, the recommended starting dose is 2.25 microg/kg once weekly by subcutaneous injection and subsequent titration. The adverse event profile of darbepoetin alfa is similar to that of recombinant human erythropoietin in both settings. There are no reports of antibody formation associated with darbepoetin alfa in chronic renal failure patients, and three cases of antibody formation, with neutralizing activity in one of the cases, have been reported in cancer patients. However, no cases of antibody-mediated pure red cell aplasia have been reported. The longer half-life of darbepoetin alfa, together with a similar efficacy and safety profile, confers the clinical advantage over recombinant human erythropoietin of allowing a less frequent dosing (once weekly or every other week versus one to three times weekly in renal patients), thus reducing health-care utilization and probably improving patient compliance.
达比泊汀α是一种开发用于治疗贫血的新型促红细胞生成蛋白。它是重组人促红细胞生成素的高糖基化类似物，作用机制与促红细胞生成素相同，但在动物模型和人类中，静脉给药后其终末半衰期比重组人促红细胞生成素和天然激素长三倍。对接受或未接受透析的慢性肾衰竭患者的临床研究表明，就血红蛋白浓度的增加、达到目标血红蛋白浓度的患者百分比以及达到目标血红蛋白浓度的平均时间而言，达比泊汀α与重组人促红细胞生成素相当，尽管达比泊汀α的给药频率较低（每周一次或每隔一周一次）。对接受或未接受化疗的癌症患者的临床试验表明，达比泊汀α在每1、2或3周一次的剂量间隔下缓解贫血是安全有效的，结果表明它在癌症患者中可能比重组人促红细胞生成素产生更大、更快的反应。此外，在这些患者中，观察到使用达比泊汀α治疗纠正贫血与健康相关生活质量的改善相关。达比泊汀α已获欧盟委员会和美国食品药品监督管理局批准用于静脉和皮下给药，以治疗慢性肾衰竭患者的贫血。此外，该产品最近获美国食品药品监督管理局批准用于治疗非髓样恶性肿瘤患者的贫血，这些患者的贫血是由同时进行的化疗作用所致。慢性肾衰竭患者的推荐起始剂量为静脉和皮下给药均为每周一次0.45微克/千克，随后根据血红蛋白浓度进行滴定。在癌症患者中，推荐起始剂量为皮下注射每周一次2.25微克/千克，随后进行滴定。在这两种情况下，达比泊汀α的不良事件谱与重组人促红细胞生成素相似。在慢性肾衰竭患者中没有与达比泊汀α相关的抗体形成报告，在癌症患者中报告了3例抗体形成病例，其中1例具有中和活性。然而，没有抗体介导的纯红细胞再生障碍性贫血病例报告。达比泊汀α较长的半衰期，连同相似的疗效和安全性，使其相对于重组人促红细胞生成素具有临床优势，即允许给药频率较低（每周一次或每隔一周一次，而肾病患者为每周一至三次），从而减少医疗保健利用并可能提高患者依从性。
