Pharmacology of TNF blockade in rheumatoid arthritis and other chronic inflammatory diseases
Pharmacology of TNF blockade in rheumatoid arthritis and other chronic inflammatory diseases
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DOI：
10.1016/j.coph.2010.01.005
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发表时间：
2010-06-01
影响因子：
4
通讯作者：
Taylor, Peter C.
中科院分区：
文献类型：
--
作者：
Taylor, Peter C.
肿瘤坏死因子-α (TNF) 已被明确验证为许多免疫介导的炎症性疾病 (IMID) 的治疗靶点。现在该类生物制剂的选择越来越多，所有这些都可以成功中和 sTNF。但 TNF 抑制方法有所不同，目前包括单克隆抗体（英夫利昔单抗、阿达木单抗和戈利木单抗）、嵌合序列或人序列、聚乙二醇化 Fab' 片段（赛妥珠单抗）和 IgG1-TNFR2 融合蛋白（依那西普）。正在出现的情况是，这三种抗 TNF 亚型的药理学特性在 Fc 功能、tmTNF 的结合及其可能的后果以及形成复合物的能力方面有所不同。每种药物的给药方式、清除率和达到的局部组织浓度也可能赋予与功效和安全性相关的独特特征。
Tumor necrosis factor-alpha (TNF) has been unequivocally validated as a therapeutic target in a number of immune-mediated inflammatory disorders (IMIDs). There is now increasing choice of biologic agents within the class all of which successfully neutralize sTNF. But approaches to TNF inhibition differ and currently include mAbs (infliximab, adalimumab, and golimumab), either chimeric or human in sequence, a PEGylated Fab' fragment (certolizumab), and an IgG1-TNFR2 fusion protein (etanercept). It is emerging that the pharmacological properties of these three anti-TNF subtypes differ with respect to Fc function, binding of tmTNF and the possible consequences of this, as well as the ability to form complexes. The mode of administration of each agent, clearance and the local tissue concentrations achieved may also confer unique characteristics of relevance with respect to efficacy and safety.