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达利珠单抗治疗多发性硬化症。

Daclizumab in multiple sclerosis.

作者信息

Perez-Miralles F C

机构信息

Hospital Universitari i Politecnic La Fe, Valencia, Espana.

出版信息

Rev Neurol. 2018 Apr 16;66(8):271-282.

Abstract

INTRODUCTION

Daclizumab is a monoclonal antibody directed against the CD25 subunit of the interleukin-2 receptor, investigated as a disease-modifying therapy in relapsing-remitting multiple sclerosis. The present review addresses how the drug was developed, the known mechanism of action of the drug and the up-to-date data of efficacy and safety.

DEVELOPMENT

Daclizumab has shown superiority in prevention of relapses against placebo and low-dose interferon beta-1a at a level that puts it on par with the rest of current first-line drugs. The effect on the progression of the disease and on neurodegeneration parameters, however, is not clear. On the other hand, it presents safety problems (mainly risk of autoimmunity phenomena including fulminant hepatopathy and encephalitis) that have supposed eventually its withdrawn from marketing. Daclizumab introduces a new mechanism of action through the blocking of a key interleukin in immune regulation and its effect on a population of cells with regulatory ability, such as the NK CD56(bright) cells.

CONCLUSIONS

Daclizumab has shown efficacy in slowing the inflammatory process of multiple sclerosis, although the appearance of potentially serious side effects has not allowed its use to significantly impact current clinical practice. The development of new drugs in multiple sclerosis must be contingent on maintaining or improving the risk-benefit profile with respect to those already in use.

摘要

引言

达利珠单抗是一种针对白细胞介素-2受体CD25亚基的单克隆抗体,作为复发缓解型多发性硬化症的疾病改善疗法进行研究。本综述探讨了该药物的研发过程、已知的作用机制以及最新的疗效和安全性数据。

研发

达利珠单抗在预防复发方面优于安慰剂和低剂量干扰素β-1a,其水平与目前其他一线药物相当。然而,其对疾病进展和神经退行性变参数的影响尚不清楚。另一方面,它存在安全问题(主要是自身免疫现象的风险,包括暴发性肝病和脑炎),最终导致其退出市场。达利珠单抗通过阻断免疫调节中的关键白细胞介素以及对具有调节能力的细胞群体(如NK CD56(bright)细胞)产生作用,引入了一种新的作用机制。

结论

达利珠单抗已显示出在减缓多发性硬化症炎症过程方面的疗效,尽管潜在严重副作用的出现使其未能在当前临床实践中产生显著影响。多发性硬化症新药的研发必须取决于维持或改善相对于现有药物的风险效益比。

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