Herlin Troels
Department of Pediatrics, Aarhus University Hospital, Skejby, Aarhus, Denmark.
Core Evid. 2010 Jun 15;4:181-9. doi: 10.2147/ce.s5992.
Juvenile idiopathic arthritis (JIA) is one of the most common chronic diseases with childhood onset. It comprises different subtypes of which the systemic onset subtype is often resistant to treatment. With the advent of biological treatment with tumor necrosis factor-alpha (TNFalpha)-inhibitors, the clinical outcome of JIA has improved considerably, but only for subtypes other than systemic JIA. Substantial evidence shows that the proinflammatory cytokine interleukin-6 (IL-6) plays a pivotal role in systemic JIA. The blockage of IL-6 action by tocilizumab, a humanized anti-IL-6-receptor monoclonal antibody, could therefore be an effective treatment of systemic JIA.
The purpose of this article was to review the clinical trials of tocilizumab and to discuss its place in the treatment of JIA with the focus on the systemic onset of disease.
Two phase II studies and one phase III clinical trial of tocilizumab demonstrating the clinical efficacy and safety in systemic onset JIA have been published. Within those studies, sustained and high response rates of clinical improvement have been achieved with American College of Rheumatology Pediatric criteria (ACRPed) 30, 50, and 70 observed in 98%, 94%, and 90% of patients, respectively, after 48 weeks. One study regarding the clinical efficacy of tocilizumab for the treatment of oligo- and polyarticular JIA has been presented only as a conference abstract.
The very promising results seen so far in patients with severe systemic JIA and acceptable tolerability gives tocilizumab a central role in the future therapy in controlling this disease. No other biological therapy has achieved similar high response rates when treating with tocilizumab 8 mg/kg every two weeks to patients with systemic onset JIA, but direct comparison of the efficacy of different biological agents are not yet available.
幼年特发性关节炎(JIA)是儿童期最常见的慢性病之一。它包含不同亚型,其中全身型亚型往往对治疗有抵抗性。随着肿瘤坏死因子-α(TNFα)抑制剂生物治疗的出现,JIA的临床结局有了显著改善,但仅针对全身型JIA以外的亚型。大量证据表明,促炎细胞因子白细胞介素-6(IL-6)在全身型JIA中起关键作用。因此,托珠单抗(一种人源化抗IL-6受体单克隆抗体)阻断IL-6的作用可能是治疗全身型JIA的有效方法。
本文旨在回顾托珠单抗的临床试验,并讨论其在JIA治疗中的地位,重点关注疾病的全身型发作。
已发表两项托珠单抗的II期研究和一项III期临床试验,证明其在全身型发作JIA中的临床疗效和安全性。在这些研究中,临床改善的持续和高反应率得以实现,48周后分别有98%、94%和90%的患者达到美国风湿病学会儿科标准(ACRPed)30、50和70。一项关于托珠单抗治疗少关节型和多关节型JIA临床疗效的研究仅作为会议摘要发表。
迄今为止,在重症全身型JIA患者中看到的非常有前景的结果以及可接受的耐受性,使托珠单抗在未来控制这种疾病的治疗中发挥核心作用。当每两周给全身型发作JIA患者使用8 mg/kg托珠单抗治疗时,没有其他生物疗法能达到类似的高反应率,但不同生物制剂疗效的直接比较尚无可用数据。