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口服芬戈莫德治疗多发性硬化症:鞘氨醇-1-磷酸系统的治疗性调节

[Oral fingolimod in multiple sclerosis: therapeutic modulation of the sphingosine-1-phosphate system].

作者信息

Aktas O, Ingwersen J, Kieseier B, Küry P, Hohlfeld R, Hartung H-P

机构信息

Neurologische Universitätsklinik, Heinrich-Heine-Universität, Düsseldorf, Deutschland.

出版信息

Nervenarzt. 2011 Feb;82(2):215-25. doi: 10.1007/s00115-010-3075-8.

Abstract

In this article the recent clinical data on novel therapy of relapsing multiple sclerosis with oral fingolimod (FTY720), lead substance of the recently described class of sphingosine-1-phosphate (S1P) receptor modulators are reviewed. Results of the two phase III studies (FREEDOMS; TRANSFORMS) corroborating previous phase II trial observations suggest that fingolimod has a strong anti-inflammatory effect in relapsing multiple sclerosis (MS), most probably by suppression of lymphocyte re-circulation from lymph nodes to inflammatory tissues (lymphocyte egress). Patients treated with fingolimod show a robust reduction of relapse frequency, compared to placebo (FREEDOMS) or an active comparator (interferon-β1a) (TRANSFORMS) and they show less inflammatory lesions on brain MR imaging. Furthermore, data from experimental research indicate that fingolimod may equally promote neural repair in vivo as well. Thus, the proposed immunological and neurobiological profile of fingolimod as well as the data from the recent clinical trials will be discussed in the context of the expected safety profile.

摘要

本文综述了新型口服药物芬戈莫德(FTY720)治疗复发型多发性硬化症的最新临床数据,FTY720是最近描述的一类鞘氨醇-1-磷酸(S1P)受体调节剂的先导物质。两项III期研究(FREEDOMS;TRANSFORMS)的结果证实了先前II期试验的观察结果,表明芬戈莫德在复发型多发性硬化症(MS)中具有强大的抗炎作用,很可能是通过抑制淋巴细胞从淋巴结向炎症组织的再循环(淋巴细胞外渗)实现的。与安慰剂(FREEDOMS)或活性对照药(干扰素-β1a)(TRANSFORMS)相比,接受芬戈莫德治疗的患者复发频率显著降低,并且在脑部磁共振成像上显示出较少的炎症性病变。此外,实验研究数据表明,芬戈莫德在体内也可能同样促进神经修复。因此,将在预期安全性概况的背景下讨论芬戈莫德提出的免疫学和神经生物学特征以及近期临床试验的数据。

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