治疗类风湿性关节炎的IL-6受体阻滞剂——Sarilumab

A IL-6 Receptor Blocker for Rheumatoid Ar-thritis—Sarilumab

摘要: 类风湿性关节炎是一种慢性全身性炎症性疾病，主要影响外周关节。Sarilumab是一种全人源化单克隆抗体，能与可溶性和膜结合白细胞介素6受体(IL-6R)特异性结合，从而抑制白细胞介素6介导的信号转导。在II期和III期临床试验中，Sarilumab在对甲氨蝶呤反应不足或对肿瘤坏死因子抑制剂反应不足或不耐受的类风湿性关节炎患者中表现出优于安慰剂的临床效果。与阿达木单抗单药治疗相比，Sarilumab单药治疗对甲氨蝶呤疗效不佳或不耐受的类风湿性关节炎患者也表现出优异的效果。Sarilumab是对常规合成的生物疾病缓解型抗风湿药物或肿瘤坏死因子α抑制剂反应不足的中度至重度活动性类风湿性关节炎患者的生物疾病缓解型抗风湿药物或靶向合成疾病缓解型抗风湿药物的替代药物。本综述总结了Sarilumab在类风湿性关节炎治疗中的作用机制、临床疗效及安全性。

Abstract: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease predominantly affecting the peripheral diarthrodial joints. Sarilumab is a fully human IgG1monoclonal antibody that binds spe-cifically to both soluble and membrane-bound interleukin (IL)-6 receptors and thereby inhibits IL-6-mediatedsignalling through these receptors. In Phase II and III clinical trials, Sarilumab in the background of methotrexate showed superior clinical efficacy over placebo in RA patients with in-adequate response to methotrexate or inadequate response or intolerance to TNF inhibitors. Sarilumab monotherapy also showed superior efficacy compared with adalimumab monotherapy in RA patients with inadequate response or intolerance to methotrexate. Sarilumab is an alternative to biologic disease-modifying anti-rheumatic drugs (DMARDs) or targeted synthetic DMARDs in patients with moderate to severely active RA who have not responded adequately to prior conventional synthetic DMARDs or tumor necrosis factor-α inhibitors. In this review, mechanism of action, clinical efficacy and safety of Sarilumab in the treatment of RA will be summarized.