Department of Infectious Disease and Microbiology, Children's Hospital at Westmead, Westmead, Australia.
Adv Exp Med Biol. 2013;764:151-8. doi: 10.1007/978-1-4614-4726-9_12.
Biologics are generally either custom-designed monoclonal antibodies against specific target cells (e.g. B-cells) or target cytokines (e.g. tumour necrosis factor, TNF) or they are receptor constructs (fusion proteins) based on naturally-occurring cytokine or cell receptors. Biologics are mostly used in adult rheumatology but are increasingly used in paediatrics. There are significant concerns about safety and also about cost. The main safety concerns are about increased risk of infection and malignancy. The use of TNF antagonists is associated with increased risk of serious infections with intracellular organisms, particularly mycobacteria, but also intracellular bacteria, fungi and Pneumocystis. B-cell antagonists like rituximab can cause progressive multifocal leukoencephalopathy. IL-6 antagonists are associated with increased rates of common bacterial infections and the complement pathway antagonist eculizumab with meningococcal infection. The risk of some infections associated with biologics can be reduced, by screening patients starting TNF antagonists for latent tuberculosis and giving them cotrimoxazole prophylaxis against Pneumocystis, and by immunising against VZV, hepatitis B, meningococci and pneumococci. However, the risk of the biologics causing serious infection in children is unknown and needs study. Children should not be started on the biologics without careful consideration of the risks and without fully informed consent.
生物制剂通常是针对特定靶细胞（例如 B 细胞）或靶细胞因子（例如肿瘤坏死因子，TNF）的定制设计的单克隆抗体，或者是基于天然细胞因子或细胞受体的受体构建体（融合蛋白）。生物制剂主要用于成人风湿病学，但在儿科中的应用越来越多。人们对其安全性和成本存在重大担忧。主要的安全问题是感染和恶性肿瘤的风险增加。TNF 拮抗剂的使用与细胞内病原体（特别是分枝杆菌），但也包括细胞内细菌、真菌和卡氏肺孢子虫的严重感染风险增加有关。B 细胞拮抗剂如利妥昔单抗可导致进行性多灶性白质脑病。IL-6 拮抗剂与常见细菌感染的发生率增加有关，补体途径拮抗剂依库珠单抗与脑膜炎奈瑟菌感染有关。通过对开始使用 TNF 拮抗剂的患者进行潜伏性结核筛查，并给予复方磺胺甲噁唑预防卡氏肺孢子虫，以及接种 VZV、乙型肝炎、脑膜炎球菌和肺炎球菌疫苗，可以降低某些与生物制剂相关的感染风险。然而，生物制剂在儿童中引起严重感染的风险尚不清楚，需要研究。在没有充分考虑风险并获得充分知情同意的情况下，不应在儿童中开始使用生物制剂。
