Safety of intravenous equine F(ab')2: Insights following clinical trials involving 1534 recipients of scorpion antivenom
Safety of intravenous equine F(ab')2: Insights following clinical trials involving 1534 recipients of scorpion antivenom
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DOI：
10.1016/j.toxicon.2013.07.017
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发表时间：
2013-12-15
期刊：
影响因子：
2.8
通讯作者：
Alagon, Alejandro
中科院分区：
文献类型：
--
作者：
Boyer, Leslie;Degan, Janice;Alagon, Alejandro
简介：抗蛇毒血清的生产技术自世纪之交最早生产抗血清以来逐渐发生了变化。早期抗血清的使用与频繁的急性不良反应和血清病相关。使用胃蛋白酶降解免疫球蛋白并沉淀不需要的蛋白质和白蛋白血清组分生产的新F（ab '）（2）产品在概念上应在临床使用中引起较少的免疫反应。马F（ab '）（2）抗蛇毒血清的一组五项前瞻性临床试验，以及一项历史对照研究，在产品开发期间完成，以通过美国FDA申请生物许可证。不良事件进行了记录和分类，特别注意免疫reactions.Results的频率：共1534例患者年龄为0.1-90.5岁，在亚利桑那州和墨西哥，蝎envenomation治疗抗蛇毒血清。总给药范围为1 - 5瓶，1个离群值除外，其接受了10瓶。估计的蛋白质暴露量为12-275 mg/患者（离群值，高达550 mg）。3例患者（0.2%）对抗蛇毒血清输注有急性反应（1例荨麻疹，1例荨麻疹和呼吸困难，1例惊恐发作）。8例（0.5%）出现皮疹，提示3型免疫反应，但没有一例出现血清病综合征。两名妇女进行了治疗envenomation在怀孕的头三个月，其中一人随后经历了自然流产。结论：该产品的免疫反应率是两个数量级低于范围（高达75%的早期和81%的晚期反应）历史上报道的使用最低限度的精制全免疫球蛋白产品对各种感染和envenomations。较低的蛋白剂量、较高纯度的活性成分、免疫球蛋白分子免疫原性Fc部分的缺乏以及缓慢的静脉内输注可能是其原因。更安全的产品的临床意义包括，它可以在抗蛇毒血清曾经被认为太危险而不能使用的环境中使用，如初级保健诊所和偏远农村地区。(C)2013爱思唯尔有限公司保留所有权利。
Introduction: The technology of antivenom production has gradually changed since the earliest production of antisera around the turn of the 20th century. Use of early antisera was associated with frequent acute adverse reactions and serum sickness. New F(ab')(2) products, manufactured using pepsin degradation of immunoglobulin together with precipitation of unwanted protein and albumin serum fractions, should in concept cause fewer immune reactions in clinical use.Methods: A linked set of five prospective clinical trials of an equine F(ab')(2) antivenom, together with one historical control study, were completed during development of the product for a Biological License Application through the US FDA. Adverse events were recorded and categorized, with particular attention to the frequency of immune reactions.Results: A total of 1534 patients ages 0.1-90.5 years received antivenom, in Arizona and in Mexico, for treatment of scorpion envenomation. Total dosing ranged from 1 to 5 vials except for one outlier who received 10 vials. Estimated protein exposure was 12-275 mg per patient (outlier, up to 550 mg). Three patients (0.2%) had acute reactions to antivenom infusion (one urticaria, one urticaria and dyspnea, and one panic attack). Eight (0.5%) had rashes suggestive of Type 3 immune reactions, although none had the full syndrome of serum sickness. Two women were treated for envenomation during the first trimester of pregnancy, one of whom subsequently experienced a spontaneous abortion.Conclusions: Rates of immune reaction to this product were two orders of magnitude lower than the range (up to 75% for early and 81% for late reactions) historically reported with use of minimally refined whole immunoglobulin products against a variety of infections and envenomations. Lower protein dose, greater purity of the active component, lack of the immunogenic Fc portion of the immunoglobulin molecule, and slow intravenous infusion are likely to be the reason for this. Clinical implications of a safer product include that it can be employed in settings where antivenom was once considered too dangerous to use, such as primary care clinics and remote rural areas. (C) 2013 Elsevier Ltd. All rights reserved.