Mavrilimumab:基于证据的类风湿关节炎治疗潜力综述

Core Evidence Pub Date : 2014-03-12 eCollection Date: 2014-01-01 DOI:10.2147/CE.S39770
Manuela Di Franco, Maria Chiara Gerardi, Bruno Lucchino, Fabrizio Conti
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引用次数: 18

摘要

类风湿性关节炎(RA)的治疗随着生物疾病修饰抗风湿药物的发展有了很大的改善,但尽管目前有生物药物可用,但仍有一部分患者的病情没有好转。我们需要具有新作用机制的新型生物制剂来治疗难治性患者。最近有证据表明,粒细胞-巨噬细胞集落刺激因子(GM-CSF)参与了RA的发病机制。GM-CSF可加重RA,在RA患者的滑液中观察到该细胞因子水平升高。GM-CSF的拮抗作用可以显著减少小鼠关节炎模型中的既定疾病。Mavrilimumab是一种人GM-CSF受体α单克隆抗体,是GM-CSF信号传导的竞争性拮抗剂。I期和II期研究显示,在轻度至中度RA患者中有良好的临床反应和良好的安全性,表明mavrilimumab治疗RA的效果令人鼓舞。本文综述了评价mavrilimumab治疗RA的安全性、耐受性和有效性的临床前和临床数据。
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Mavrilimumab: an evidence based review of its potential in the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) management has greatly improved with the development of biologic disease modifying antirheumatic drugs, but a proportion of patients do not improve despite the biologic drugs currently available. We need new biologic agents with novel mechanisms of action for the treatment of refractory patients. Recent evidence has shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) is involved in the pathogenesis of RA. GM-CSF can exacerbate RA and elevated levels of this cytokine have been observed in synovial fluid from RA patients. Antagonism of GM-CSF can strikingly reduce established disease in mouse models of arthritis. Mavrilimumab, a human monoclonal antibody to GM-CSF receptor α, is a competitive antagonist of GM-CSF signaling. Phase I and II studies have shown good clinical response with a good safety profile in patients with mild to moderate RA, suggesting encouraging effects of mavrilimumab for the treatment of RA. This paper reviews the preclinical and clinical data evaluating the safety, tolerability, and efficacy of mavrilimumab in the treatment of RA.

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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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