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复发缓解型多发性硬化症新出现疗法的最新进展

An update on new and emerging therapies for relapsing-remitting multiple sclerosis.

作者信息

Weinstock-Guttman Bianca

出版信息

Am J Manag Care. 2013 Nov;19(17 Suppl):s343-54.

PMID:24494635
Abstract

Disease-modifying therapies (DMTs), known to actively reduce relapses and delay disability progression, have been used for the treatment of relapsing-remitting multiple sclerosis (RRMS) for over a decade. These well-known therapies include intramuscular (IM) interferon (IFN) beta-1a (Avonex), subcutaneous (SC) IFN beta-1a (Rebif), SC IFN beta- 1b (Betaseron; Extavia), and SC glatiramer acetate (Copaxone). These first-line therapies have shown only partial benefits for controlling multiple sclerosis (MS) disease activity and are often associated with inadequate patient adherence. Low patient adherence to therapy may be related to the mode of administration or to the side effects associated with treatment. The intravenous DMT natalizumab (Tysabri; dosed monthly) provides high therapeutic efficacy and good compliance but is considered a second-line intervention because of the associated increased risk for progressive multifocal leukoencephalopathy. In 2010, fingolimod (Gilenya), the first oral DMT, was approved by the US Food and Drug Administration (FDA) for the treatment of MS. Recently, 2 new oral DMTs received FDA approval for the treatment of RRMS: teriflunomide (Aubagio) and dimethyl fumarate (Tecfidera). In addition, oral laquinimod, several monoclonal antibodies (eg, alemtuzumab, daclizumab, and ocrelizumab), and other agents have shown preliminary beneficial results in relapsing MS in phase 3 clinical trials. These new and emerging DMTs may provide a more efficacious individualized therapeutic approach, more favorable methods of administration (eg, oral administration), and/or a lower frequency of infusions (eg, annually, 3-5 daily infusions over a year for alemtuzumab) that may improve patient adherence and clinical outcomes.

摘要

疾病修饰疗法(DMTs)已知可有效减少复发并延缓残疾进展,十多年来一直用于复发缓解型多发性硬化症(RRMS)的治疗。这些广为人知的疗法包括肌肉注射(IM)干扰素(IFN)β-1a(阿沃尼)、皮下注射(SC)IFNβ-1a(利比)、SC IFNβ-1b(倍泰龙;复迈)以及SC醋酸格拉替雷(考帕松)。这些一线疗法在控制多发性硬化症(MS)疾病活动方面仅显示出部分益处,且常与患者依从性不足相关。患者对治疗的低依从性可能与给药方式或治疗相关的副作用有关。静脉注射DMT那他珠单抗(泰萨比;每月给药一次)具有高治疗效果和良好的依从性,但由于相关的进行性多灶性白质脑病风险增加,被视为二线干预措施。2010年,首个口服DMT芬戈莫德(捷灵亚)获美国食品药品监督管理局(FDA)批准用于治疗MS。最近,两种新型口服DMT获FDA批准用于治疗RRMS:特立氟胺(奥巴捷)和富马酸二甲酯(捷倍安)。此外,口服拉喹莫德、几种单克隆抗体(如阿仑单抗、达利珠单抗和奥瑞珠单抗)以及其他药物在3期临床试验中对复发型MS已显示出初步有益结果。这些新兴的DMTs可能提供更有效的个体化治疗方法、更有利的给药方式(如口服给药)和/或更低的输注频率(如每年一次,阿仑单抗为每年3 - 5次每日输注),这可能会提高患者的依从性和临床疗效。

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