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醋酸格拉替雷治疗多发性硬化症。作用机制、药代动力学、不良反应概况及临床研究的当前情况

[Treatment of multiple sclerosis with glatiramer acetate. Current aspects of mechanisms of action, pharmacokinetics, adverse effect profile and clinical studies].

作者信息

Ziemssen T, Neuhaus O, Farina C, Hartung H P, Hohlfeld R

机构信息

Abteilung für Neuroimmunologie, Max-Planck-Institut für Neurobiologie, Martinsried.

出版信息

Nervenarzt. 2002 Apr;73(4):321-31. doi: 10.1007/s00115-001-1257-0.

DOI:10.1007/s00115-001-1257-0
PMID:12040979
Abstract

Glatiramer acetate (GA, Copaxone), a standardized mixture of synthetic polypeptides, has now been approved also in Germany for the treatment of relapsing-remitting multiple sclerosis (RR-MS). After it had been shown effective in suppression of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), it was evaluated in several clinical studies. In these studies, GA could alter the natural history of MS by both reducing the relapse rate and affecting disability. The clinical therapeutic effect of GA was consistent with the effect on magnetic resonance imaging-defined disease activity and burden in a recent multicenter study. As a daily standard dose, 20 mg of GA is injected subcutaneously. The induction of GA-reactive T-helper 2-like regulatory suppressor cells is thought to be the main mechanism of action. The most common adverse effects are mild injection site reactions. A remarkable but rare adverse effect is the only transient immediate post-injection systemic reaction manifested by flushing, chest tightness, palpitations, and dyspnea. Antibodies to GA which are induced during GA treatment do not interfere with its clinical effects.

摘要

醋酸格拉替雷(GA,考帕松)是一种合成多肽的标准化混合物,现已在德国获批用于治疗复发缓解型多发性硬化症(RR-MS)。在其被证明对多发性硬化症(MS)的动物模型实验性自身免疫性脑脊髓炎(EAE)有抑制作用后,又进行了多项临床研究对其进行评估。在这些研究中,GA通过降低复发率和影响残疾程度,能够改变MS的自然病程。在最近一项多中心研究中,GA的临床治疗效果与对磁共振成像定义的疾病活动和负担的影响一致。作为每日标准剂量,20mg GA皮下注射。GA反应性辅助性T细胞2样调节性抑制细胞的诱导被认为是主要作用机制。最常见的不良反应是轻微的注射部位反应。一种显著但罕见的不良反应是仅在注射后立即出现的短暂全身反应,表现为脸红、胸闷、心悸和呼吸困难。GA治疗期间诱导产生的抗GA抗体并不干扰其临床效果。

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1
[Treatment of multiple sclerosis with glatiramer acetate. Current aspects of mechanisms of action, pharmacokinetics, adverse effect profile and clinical studies].醋酸格拉替雷治疗多发性硬化症。作用机制、药代动力学、不良反应概况及临床研究的当前情况
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In vitro evidence that subcutaneous administration of glatiramer acetate induces hyporesponsive T cells in patients with multiple sclerosis.皮下注射醋酸格拉替雷能诱导多发性硬化症患者体内产生低反应性T细胞的体外证据。
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