Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands.
Nat Rev Rheumatol. 2013 Mar;9(3):164-72. doi: 10.1038/nrrheum.2013.4. Epub 2013 Feb 12.
Currently, five anti-TNF biologic agents are approved for the treatment of rheumatoid arthritis (RA): adalimumab, infliximab, etanercept, golimumab and certolizumab pegol. Formation of anti-drug antibodies (ADA) has been associated with all five agents. In the case of adalimumab and infliximab, immunogenicity is strongly linked to subtherapeutic serum drug levels and a lack of clinical response, but for the other three agents, data on immunogenicity are scarce, suggesting that further research would be valuable. Low ADA levels might not influence the efficacy of anti-TNF therapy, whereas high ADA levels impair treatment efficacy by considerably reducing unbound drug levels. Immunogenicity is not only an issue in patients treated with anti-TNF biologic agents; the immunogenicity of other therapeutic proteins, such as factor VIII and interferons, is well known and has been investigated for many years. The results of such studies suggest that investigations to determine the optimal treatment regimen (drug dosing, treatment schedule and co-medication) required to minimize the likelihood of ADA formation might be an effective and practical way to deal with the immunogenicity of anti-TNF biologic agents for RA.
目前，有五种抗 TNF 生物制剂被批准用于治疗类风湿关节炎（RA）：阿达木单抗、英夫利昔单抗、依那西普、戈利木单抗和培塞利珠单抗。所有这五种药物都与形成抗药物抗体（ADA）有关。对于阿达木单抗和英夫利昔单抗，免疫原性与治疗性血清药物水平低和缺乏临床反应密切相关，但对于其他三种药物，免疫原性的数据很少，表明进一步的研究将是有价值的。ADA 水平低可能不会影响抗 TNF 治疗的疗效，而 ADA 水平高会通过显著降低游离药物水平来损害治疗效果。免疫原性不仅是接受抗 TNF 生物制剂治疗的患者的一个问题；其他治疗性蛋白（如因子 VIII 和干扰素）的免疫原性也是众所周知的，并且已经研究了多年。这些研究的结果表明，为确定可最大程度降低 ADA 形成可能性所需的最佳治疗方案（药物剂量、治疗方案和联合用药）进行的研究可能是处理 RA 抗 TNF 生物制剂免疫原性的有效且实用的方法。
