Friedrich-Alexander University Erlangen-Nürnberg, Division of Molecular Immunology, Nikolaus-Fiebiger Center, Glückstraße 6, D-91054 Erlangen, Germany.
Ludwig-Maximilians-University, Division of Rheumatology and Clinical Immunology, Department of Internal Medicine IV, Pettenkoferstraße 8a, D-80336 Munich, Germany.
Nat Rev Rheumatol. 2017 Nov 21;13(12):707-718. doi: 10.1038/nrrheum.2017.187.
The availability of monoclonal antibodies has revolutionized the treatment of an increasingly broad spectrum of diseases. Inflammatory diseases are among those most widely treated with protein-based therapeutics, termed biologics. Following the first large-scale clinical trials with monoclonal antibodies performed in the 1990s by rheumatologists and clinical immunologists, the approval of these agents for use in daily clinical practice led to substantial progress in the treatment of rheumatic diseases. Despite this progress, however, only a proportion of patients achieve a long-term clinical response. Data on the use of agents blocking TNF, which were among the first biologics introduced into clinical practice, provide ample evidence of primary and secondary treatment inefficacy in patients with rheumatoid arthritis (RA). Important issues relevant to primary and secondary failure of these agents in RA include immunogenicity, methodological problems for the detection of antidrug antibodies and trough drug levels, and the implications for treatment strategies. Although there is no strong evidence to support the routine estimation of antidrug antibodies or serum trough levels during anti-TNF therapy, these assessments might be helpful in a few clinical situations; in particular, they might guide decisions on switching the therapeutic biologic in certain instances of secondary clinical failure.
单克隆抗体的出现彻底改变了对越来越广泛疾病谱的治疗。在使用蛋白质类治疗药物（称为生物制剂）治疗的疾病中，炎症性疾病是最广泛的一种。在 20 世纪 90 年代，风湿病学家和临床免疫学家首次进行了大规模的单克隆抗体临床试验，随后这些药物获得批准用于日常临床实践，从而推动了风湿性疾病的治疗取得了实质性进展。然而，尽管取得了这一进展，但只有一部分患者获得了长期的临床缓解。在使用阻断 TNF 的药物方面的数据表明，这些药物是最早引入临床实践的生物制剂之一，为类风湿关节炎 (RA) 患者的原发性和继发性治疗无效提供了充分的证据。这些药物在 RA 中出现原发性和继发性失败的重要问题包括免疫原性、用于检测抗药物抗体和药物谷浓度的方法学问题，以及对治疗策略的影响。尽管没有强有力的证据支持在抗 TNF 治疗期间常规评估抗药物抗体或血清药物谷浓度，但在某些临床情况下，这些评估可能会有所帮助；特别是，在某些继发性临床治疗失败的情况下，它们可能有助于指导关于转换治疗性生物制剂的决策。
