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多发性硬化症治疗的最新进展;当前针对多发性硬化症的新型特效药物

Recent Advances in the Treatment for Multiple Sclerosis; Current New Drugs Specific for Multiple Sclerosis.

作者信息

TaŞKapilioĞLu ÖZlem

机构信息

Department of Neurology, Mehmet Ali Aydınlar Acıbadem University School of Medicine, İstanbul, Turkey.

出版信息

Noro Psikiyatr Ars. 2018;55(Suppl 1):S15-S20. doi: 10.29399/npa.23402.

Abstract

Since the first approved parenteral drug for the treatment of multiple sclerosis (MS) in 1993 (interferon [IFN] beta, and later glatiramer acetate [GA]), today there are both parenteral and oral treatment options for MS. After IFN beta preparations, glatiramer acetate was developed; and, until the approval of natalizumab in 2006, those dominated the treatment of MS. Later on, among oral drug options, cladribine made a promising entry; however, due to safety concerns, it was withdrawn soon. Afterwards, with the understanding of the role of sphingosine-1 phosphate (S1P) receptors in the pathogenesis of MS, fingolimod was approved in 2010, which was followed by other oral agents such as teriflunomide and dimethyl fumarate. Recently newer IV treatment options such as alemtuzumab, rituximab and ocrelizumab have widened the treatment arena. Recently, after submitting new efficacy and safety data, cladribine was approved for MS by EMA, in 2017. Moreover, seven years after its rejection due to safety reasons, in August 2018 FDA accepted to re-evaluate the data of cladribine as a treatment option for relapsing remitting MS (RRMS). Another oral treatment option, Laquinimod, was not approved because it could not be shown to slow disability progression despite favourable effect in relapsing MS. Newer generation S1P receptor modulators are being investigated currently, and they are expected to come into the treatment arena soon. In this article, mechanisms of actions, clinical trial results, and side effects of the newer drugs used for MS, are reviewed. IFN beta and glatiramer acetate were not included since they have clinical experience nearing 30 years.

摘要

自1993年第一种被批准用于治疗多发性硬化症(MS)的肠胃外给药药物(干扰素[IFN]β,随后是醋酸格拉替雷[GA])问世以来,如今治疗MS既有肠胃外给药也有口服给药的选择。在IFNβ制剂之后,开发出了醋酸格拉替雷;在2006年那他珠单抗获批之前,这些药物主导着MS的治疗。后来,在口服药物选择中,克拉屈滨有了令人期待的进展;然而,出于安全考虑,它很快就被撤市了。此后,随着对1-磷酸鞘氨醇(S1P)受体在MS发病机制中作用的认识,芬戈莫德于2010年获批,随后又有其他口服药物如特立氟胺和富马酸二甲酯。最近,诸如阿仑单抗、利妥昔单抗和奥瑞珠单抗等更新的静脉治疗选择拓宽了治疗领域。最近,在提交了新的疗效和安全性数据后,克拉屈滨于2017年被欧洲药品管理局(EMA)批准用于治疗MS。此外,在因安全原因被拒七年后,2018年8月美国食品药品监督管理局(FDA)同意重新评估克拉屈滨作为复发缓解型MS(RRMS)治疗选择的数据。另一种口服治疗选择拉喹莫德未获批准,因为尽管它对复发型MS有良好效果,但未能证明其能减缓残疾进展。新一代S1P受体调节剂目前正在研究中,预计很快会进入治疗领域。在本文中,将对用于治疗MS的更新药物的作用机制、临床试验结果和副作用进行综述。IFNβ和醋酸格拉替雷未被纳入,因为它们已有近30年的临床经验。

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