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重组人源化抗IL-6受体抗体托珠单抗,一种治疗类风湿性关节炎的创新药物。

The recombinant humanized anti-IL-6 receptor antibody tocilizumab, an innovative drug for the treatment of rheumatoid arthritis.

作者信息

Ohsugi Yoshiyuki, Kishimoto Tadamitsu

机构信息

Scientific Director Chugai Pharmaceutical Co. Ltd, 2-1-1 Nihonbashi-muromachi, Chuo-ku, Tokyo 103-8324, Japan.

出版信息

Expert Opin Biol Ther. 2008 May;8(5):669-81. doi: 10.1517/14712598.8.5.669.

Abstract

BACKGROUND

IL-6 is a pro-inflammatory cytokine with multiple roles in the pathogenesis of rheumatoid arthritis (RA). Targeting IL-6 with the humanized anti IL-6 receptor antibody tocilizumab was effective in several placebo-controlled clinical studies in RA.

OBJECTIVES

To address how clinically efficacious blockade of IL-6 signalling with inteleukin-6 receptor antibody is in RA patients and what the potential mode of action explaining tocilizumab activity in RA treatment could be.

RESULTS/CONCLUSION: IL-6 induces autoantibody-producing plasma cells and effector T cells and is implicated in the development of clinical signs and symptoms, including increased synthesis of acute phase reactants, fatigue, anaemia and anorexia. Its effects also included significant improvements in American College of Rheumatology (ACR)20, ACR50 and ACR70 values, as well as in health-related quality of life measures, compared with controls. Tocilizumab also prevents radiographic progression of joint damage. Tocilizumab is generally well tolerated and efficacious in patients refractive to conventional DMARD therapies.

摘要

背景

白细胞介素-6(IL-6)是一种促炎细胞因子,在类风湿关节炎(RA)的发病机制中具有多种作用。在多项针对RA的安慰剂对照临床研究中,使用人源化抗IL-6受体抗体托珠单抗靶向IL-6显示出疗效。

目的

探讨用白细胞介素-6受体抗体阻断IL-6信号通路在RA患者中的临床疗效如何,以及解释托珠单抗在RA治疗中活性的潜在作用模式可能是什么。

结果/结论:IL-6诱导产生自身抗体的浆细胞和效应T细胞,并与包括急性期反应物合成增加、疲劳、贫血和厌食在内的临床体征和症状的发展有关。与对照组相比,其作用还包括美国风湿病学会(ACR)20、ACR50和ACR70值以及健康相关生活质量指标有显著改善。托珠单抗还可防止关节损伤的影像学进展。托珠单抗在对传统改善病情抗风湿药(DMARD)治疗无效的患者中通常耐受性良好且有效。

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