Osaka University, Graduate School of Engineering, Division of Applied Chemistry, Department of Immuno-Medical Science , Osaka , Japan.
Expert Opin Drug Metab Toxicol. 2015 Feb;11(2):307-16. doi: 10.1517/17425255.2015.992779. Epub 2014 Dec 10.
Dysregulated overproduction of IL-6 has important roles in the pathogenesis of rheumatoid arthritis (RA). Tocilizumab (TCZ) is the only approved biologic agent inhibiting the IL-6 pathway for RA treatment, and is the focus of this review.
This review summarizes the pharmacologic characteristics, clinical efficacy and safety profile of TCZ therapy in RA patients. The data reviewed were based mainly on Phase III randomized clinical trials and the literature until 2014 regarding TCZ in RA treatment.
Being a first-line biologic agent for RA, TCZ is especially suitable for RA patients who have shown an inadequate response to TNF-α inhibitors or who cannot tolerate methotrexate. In view of its advantage in suppressing acute-phase reactions and as the only approved inhibitor of IL-6 signaling, TCZ might be particularly effective for RA patients with a high systemic inflammatory response, anemia, AA amyloidosis and other diseases mediated by IL-6. Being able to identify reliable predictors of response to TCZ, and finding more effective new biologic and treatment options, will reduce the number of patients who fail to respond to TCZ.
白细胞介素 6(IL-6)的失调过度产生在类风湿关节炎(RA)的发病机制中具有重要作用。托珠单抗(TCZ)是唯一被批准用于治疗 RA 的抑制 IL-6 通路的生物制剂,是本综述的重点。
本综述总结了 TCZ 治疗 RA 患者的药理学特征、临床疗效和安全性概况。综述中使用的数据主要基于 III 期随机临床试验和 2014 年之前关于 TCZ 在 RA 治疗中的文献。
作为 RA 的一线生物制剂,TCZ 特别适用于对 TNF-α 抑制剂反应不足或不能耐受甲氨蝶呤的 RA 患者。鉴于其抑制急性期反应的优势,以及作为唯一被批准的 IL-6 信号抑制剂,TCZ 可能对全身性炎症反应高、贫血、AA 淀粉样变性和其他由 IL-6 介导的疾病的 RA 患者特别有效。能够识别出对 TCZ 有反应的可靠预测因子,并找到更有效的新型生物制剂和治疗选择,将减少对 TCZ 反应不佳的患者数量。