B lymphocyte, BAFF and Autoimmunity Laboratory, Department of Immunology, Monash University, Level 2, AMREP Building, 89 Commercial Road, Melbourne, Victoria 3004, Australia.
Ann Rheum Dis. 2013 Feb;72(2):165-78. doi: 10.1136/annrheumdis-2012-202545. Epub 2012 Nov 24.
The introduction of biologics, especially tumour necrosis factor (TNF) inhibitors, has revolutionized the management of chronic inflammatory diseases. However, at least one third of patients with these diseases, receiving TNF inhibitors either do not respond to treatment, or lose initial responsiveness. For a significant proportion, improvement of clinical response is achieved after switching to another anti-TNF drug, suggesting a basis for failure unrelated to the therapeutic target itself. A likely explanation for this is immunogenicity, as all biologics are potentially immunogenic, and the resulting anti-drug antibodies (ADAb) can theoretically decrease the efficacy of biologics and/or induce adverse events. Indeed, in these chronic inflammatory diseases, many studies have now established correlations between ADAb formation, low serum drug levels, and the failure or loss of response to anti-TNF antibodies. This article will review key findings related to ADAb, and propose a model wherein monitoring of drug levels and ADAb may be a predictive tool leading to a better choice of biologics. Such an approach could improve chronic inflammatory disease management toward a personalized and more cost-effective approach.
生物制剂的引入，特别是肿瘤坏死因子（TNF）抑制剂的引入，彻底改变了慢性炎症性疾病的治疗方法。然而，这些疾病患者中至少有三分之一，在接受 TNF 抑制剂治疗时要么没有反应，要么最初的反应消失了。对于很大一部分患者来说，在转换为另一种抗 TNF 药物后，临床反应得到了改善，这表明治疗失败的原因与治疗靶点本身无关。一个可能的解释是免疫原性，因为所有的生物制剂都有潜在的免疫原性，由此产生的抗药物抗体（ADAb）理论上可以降低生物制剂的疗效和/或诱导不良反应。事实上，在这些慢性炎症性疾病中，许多研究现在已经建立了 ADAb 形成、血清药物水平降低与抗 TNF 抗体失效或丧失反应之间的相关性。本文将回顾与 ADAb 相关的关键发现，并提出一个模型，即监测药物水平和 ADAb 可能是一种预测工具，可以更好地选择生物制剂。这种方法可以改善慢性炎症性疾病的管理，朝着更个性化和更具成本效益的方法发展。
