Pure red-cell aplasia and epoetin therapy
Pure red-cell aplasia and epoetin therapy
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DOI：
10.1056/nejmoa040528
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发表时间：
2004-09-30
影响因子：
158.5
通讯作者：
Casadevall, N
中科院分区：
文献类型：
--
作者：
Bennett, CL;Luminari, S;Casadevall, N
背景：1988年至1998年间，有3例接受重组人促红细胞生成素（epoetin）治疗的患者报告了抗体相关的纯红细胞发育不全。1998年至2000年间，法国报告了13例此类病例——12例患者接受了Eprex配方的epoetin α， 1例患者接受了neorecmon（一种epoetin β配方）；两者都是在美国以外销售的产品。方法：我们从美国食品和药物管理局以及Eprex、Epogen（另一种促红细胞生成素α的制剂）和neorecmon的制造商那里获得了促红细胞生成素相关的纯红细胞发育不全的报告。根据产品、贫血的原因、给药途径、发现纯红细胞发育不全的国家和报告纯红细胞发育不全的日期，分析病例报告的数量和暴露调整发生率的估计。结果：1998年1月至2004年4月，共报告依普瑞、neorecmon、依普健5例与依普瑞相关的纯红细胞发育不全175例。半数以上的病例发生在法国、加拿大、英国和西班牙。2001年至2003年期间，经暴露调整后的发病率估计为：不含人血清白蛋白的Eprex制剂为每10万患者年18例，含人血清白蛋白的Eprex制剂为每10万患者年6例，neorecmon为每10万患者年1例，Epogen为每10万患者年0.2例。在对慢性肾病患者采用适当的储存、处理和给药程序后，世界范围内经暴露调整的发生率下降了83%。结论：在2001年Eprex相关的纯红细胞发育不全发生率达到峰值后，针对全球药物监测项目设计的干预措施使Eprex引起的纯红细胞发育不全发生率降低了80%以上。
BACKGROUND:Between 1988 and 1998, antibody-associated pure red-cell aplasia was reported in three patients who had undergone treatment with recombinant human erythropoietin (epoetin). Between 1998 and 2000, 13 such cases were reported from France -- 12 in patients who had received the Eprex formulation of epoetin alfa and 1 in a patient who had received Neorecormon (a formulation of epoetin beta); both are products that are marketed outside the United States.METHODS:We obtained reports of epoetin-associated pure red-cell aplasia from the Food and Drug Administration and from the manufacturers of Eprex, Epogen (another formulation of epoetin alfa), and Neorecormon. The numbers of case reports and estimates of exposure-adjusted incidence were analyzed according to the product, the cause of anemia, the route of administration, the country in which pure red-cell aplasia was identified, and the date on which pure red-cell aplasia was reported.RESULTS:Between January 1998 and April 2004, 175 cases of epoetin-associated pure red-cell aplasia were reported for Eprex, 11 cases for Neorecormon, and 5 cases for Epogen. Over half these cases had occurred in France, Canada, the United Kingdom, and Spain. Between 2001 and 2003, the estimated exposure-adjusted incidence was 18 cases per 100,000 patient-years for the Eprex formulation without human serum albumin, 6 per 100,000 patient-years for the Eprex formulation with human serum albumin, 1 case per 100,000 patient-years for Neorecormon, and 0.2 case per 100,000 patient-years for Epogen. After procedures were adopted to ensure appropriate storage, handling, and administration of Eprex to patients with chronic kidney disease, the exposure-adjusted incidence decreased by 83 percent worldwide.CONCLUSIONS:After the peak incidence of Eprex-associated pure red-cell aplasia was reached in 2001, interventions designed in response to drug-monitoring programs worldwide resulted in a reduction of more than 80 percent in the incidence of pure red-cell aplasia due to Eprex.