Rubbert-Roth Andrea, Furst Daniel E, Nebesky Jan Michael, Jin Angela, Berber Erhan
Kantonsspital St Gallen, St Gallen, Switzerland.
Clinic for Rheumatology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Rheumatol Ther. 2018 Jun;5(1):21-42. doi: 10.1007/s40744-018-0102-x. Epub 2018 Mar 3.
Tocilizumab (TCZ) is the first humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody approved for the treatment of patients with rheumatoid arthritis (RA), Castleman's disease, polyarticular and systemic juvenile idiopathic arthritis, and, most recently, giant cell arteritis as well as for the treatment of chimeric antigen receptor T cell therapy-induced cytokine release syndrome. The global clinical development program for TCZ provides a wealth of clinical data on intravenous TCZ, and more recent studies in patients with RA have provided evidence characterizing the role of intravenous TCZ as monotherapy in early disease and led to the introduction of a subcutaneous formulation of TCZ. In addition, recently published open-label extension and observational studies continue to support the long-term efficacy and safety of TCZ in both clinical trial and real-world settings. Given the involvement of IL-6-mediated signaling in inflammatory disorders, TCZ is also being investigated in other immunological diseases. In particular, a phase 2 trial on the safety and efficacy of subcutaneous TCZ in adults with systemic sclerosis shows clinically relevant improvements in skin sclerosis and lung function in these patients. Another anti-IL-6 receptor agent, sarilumab, targeting the IL6 receptor alpha subunit, was recently approved for the treatment of patients with RA, although long-term data for this biologic are not yet published. In this article we review the placement of TCZ in current treatment guidelines; recent clinical trial data, including quality of life in patients with RA; recent updates to the TCZ safety profile; recent investigations of TCZ in other immunological diseases; and the clinical development of other novel IL-6-targeted agents.
托珠单抗(TCZ)是首个被批准用于治疗类风湿关节炎(RA)、Castleman病、多关节型及全身型幼年特发性关节炎患者的人源化抗白细胞介素-6(IL-6)受体单克隆抗体,最近还被批准用于治疗巨细胞动脉炎以及嵌合抗原受体T细胞疗法诱导的细胞因子释放综合征。TCZ的全球临床开发项目提供了大量关于静脉注射TCZ的临床数据,最近针对RA患者的研究提供了证据,表明静脉注射TCZ作为早期疾病单一疗法的作用,并促使了皮下注射剂型的推出。此外,最近发表的开放标签扩展研究和观察性研究继续支持TCZ在临床试验和现实环境中的长期疗效和安全性。鉴于IL-6介导的信号传导参与炎症性疾病,TCZ也正在其他免疫性疾病中进行研究。特别是,一项关于皮下注射TCZ治疗成年系统性硬化症患者安全性和有效性的2期试验显示,这些患者的皮肤硬化和肺功能有临床相关改善。另一种抗IL-6受体药物,靶向IL-6受体α亚基的萨瑞鲁单抗,最近被批准用于治疗RA患者,不过这种生物制剂的长期数据尚未公布。在本文中,我们回顾了TCZ在当前治疗指南中的地位;最近的临床试验数据,包括RA患者的生活质量;TCZ安全性概况的最新更新;TCZ在其他免疫性疾病中的最新研究;以及其他新型IL-6靶向药物的临床开发情况。