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Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI): significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition therapy.甲氨蝶呤反应不足的类风湿关节炎患者使用活性对照托珠单抗单药治疗的研究(SATORI):通过IL-6受体抑制疗法显著降低疾病活动度和血清血管内皮生长因子水平
Mod Rheumatol. 2009;19(1):12-9. doi: 10.1007/s10165-008-0125-1. Epub 2008 Nov 1.
2
Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study.使用托珠单抗抑制白细胞介素-6受体可降低对改善病情抗风湿药物反应不足的类风湿关节炎患者的疾病活动度:托珠单抗联合传统改善病情抗风湿药物治疗研究
Arthritis Rheum. 2008 Oct;58(10):2968-80. doi: 10.1002/art.23940.
3
Update on biologics in juvenile idiopathic arthritis.青少年特发性关节炎生物制剂的最新进展。
Curr Opin Rheumatol. 2008 Sep;20(5):613-8. doi: 10.1097/BOR.0b013e3283060778.
4
IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial.用托珠单抗抑制白细胞介素-6受体可改善对抗肿瘤坏死因子生物制剂难治的类风湿关节炎患者的治疗效果:一项为期24周的多中心随机安慰剂对照试验的结果
Ann Rheum Dis. 2008 Nov;67(11):1516-23. doi: 10.1136/ard.2008.092932. Epub 2008 Jul 14.
5
Safety and efficacy of up to eight years of continuous etanercept therapy in patients with juvenile rheumatoid arthritis.青少年类风湿关节炎患者连续使用依那西普治疗长达八年的安全性和有效性。
Arthritis Rheum. 2008 May;58(5):1496-504. doi: 10.1002/art.23427.
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Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial.托珠单抗治疗全身型幼年特发性关节炎患者的疗效和安全性:一项随机、双盲、安慰剂对照、撤药期III期试验
Lancet. 2008 Mar 22;371(9617):998-1006. doi: 10.1016/S0140-6736(08)60454-7.
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Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial.托珠单抗抑制白细胞介素-6受体对类风湿关节炎患者的影响(OPTION研究):一项双盲、安慰剂对照的随机试验。
Lancet. 2008 Mar 22;371(9617):987-97. doi: 10.1016/S0140-6736(08)60453-5.
8
Incidence and characteristics of arthritis in Norwegian children: a population-based study.挪威儿童关节炎的发病率及特征:一项基于人群的研究。
Pediatrics. 2008 Feb;121(2):e299-306. doi: 10.1542/peds.2007-0291. Epub 2008 Jan 28.
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Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France.白细胞介素-1受体拮抗剂(阿那白滞素)治疗全身型幼年特发性关节炎或成人斯蒂尔病患者:法国的初步经验。
Ann Rheum Dis. 2008 Mar;67(3):302-8. doi: 10.1136/ard.2007.076034. Epub 2007 Oct 18.
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Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab.用于类风湿性关节炎的活性对照单药治疗研究,一种白细胞介素-6抑制剂(SAMURAI):托珠单抗的X线阅片者盲法随机对照试验的临床和影像学获益证据
Ann Rheum Dis. 2007 Sep;66(9):1162-7. doi: 10.1136/ard.2006.068064. Epub 2007 May 7.

托珠单抗:其在幼年特发性关节炎治疗中地位的证据

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

作者信息

Herlin Troels

机构信息

Department of Pediatrics, Aarhus University Hospital, Skejby, Aarhus, Denmark.

出版信息

Core Evid. 2010 Jun 15;4:181-9. doi: 10.2147/ce.s5992.

DOI:10.2147/ce.s5992
PMID:20694074
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2899792/
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.

摘要

引言

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。

目的

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。

证据综述

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。

治疗中的地位

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。