Tocilizumab: The evidence for its place in the treatment of juvenile idiopathic arthritis.

Core Evidence Pub Date : 2010-06-15 DOI:10.2147/ce.s5992
Troels Herlin
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Abstract

Introduction: 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.

Aims: 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.

Evidence review: 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.

Place in therapy: 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.

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托珠单抗:其在青少年特发性关节炎治疗中的地位的证据。
青少年特发性关节炎(JIA)是儿童期发病最常见的慢性疾病之一。它包括不同的亚型,其中全身性亚型通常对治疗有抵抗力。随着肿瘤坏死因子- α (TNFalpha)抑制剂生物治疗的出现,JIA的临床预后有了显著改善,但仅限于系统性JIA以外的亚型。大量证据表明,促炎细胞因子白介素-6 (IL-6)在系统性JIA中起关键作用。因此,tocilizumab(一种人源抗IL-6受体单克隆抗体)阻断IL-6的作用可能是系统性JIA的有效治疗方法。目的:本文的目的是回顾tocilizumab的临床试验,并讨论其在JIA治疗中的地位,重点是疾病的全身发病。证据综述:tocilizumab的两项II期研究和一项III期临床试验已经发表,证明了tocilizumab在全身性JIA中的临床疗效和安全性。在这些研究中,根据美国风湿病学会儿科标准(ACRPed) 30、50和70,48周后分别在98%、94%和90%的患者中观察到持续和高的临床改善缓解率。一项关于托珠单抗治疗寡关节和多关节JIA临床疗效的研究仅作为会议摘要发表。应用于治疗:迄今为止在严重全身性JIA患者中看到的非常有希望的结果和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。tocilizumab每2周8 mg/kg治疗全身性JIA患者时,没有其他生物疗法达到类似的高有效率,但目前还没有直接比较不同生物药物的疗效。
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Core Evidence
Core Evidence PHARMACOLOGY & PHARMACY-
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期刊介绍: Core Evidence evaluates the evidence underlying the potential place in therapy of drugs throughout their development lifecycle from preclinical to postlaunch. The focus of each review is to evaluate the case for a new drug or class in outcome terms in specific indications and patient groups The emerging evidence on new drugs is reviewed at key stages of development and evaluated against unmet needs
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