Vargas Diana L, Tyor William R
Department of Neurology, Emory University School of Medicine, Neurology Service, Atlanta VA Medical Center, Decatur, Georgia, USA.
J Investig Med. 2017 Jun;65(5):883-891. doi: 10.1136/jim-2016-000339. Epub 2017 Jan 27.
Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system (CNS). It predominantly affects young women and is one of the most common causes of disability in young adults. MS is characterized by formation of white matter lesions in the CNS as a result of inflammation, demyelination, and axonal loss. Treatment has been a focus of neurological research for over 60 years. A number of disease-modifying therapies (DMTs) have become available making MS a treatable disease. These compounds target the inflammatory response in MS. They work by decreasing the chances of relapse, decreasing the chances of new lesion formation seen on MRI of the CNS and slowing the accumulation of disability. The first drugs for MS to be available were interferon-β and glatiramer acetate. These work by modulating the inflammatory response via different mechanisms that are briefly discussed. Newer agents have since become available and have significantly changed the dynamics of MS treatment. These include fingolimod, dimethyl fumarate and teriflunomide, which are oral agents. Other second-line and third-line Food and Drug Administration (FDA) approved medications include natalizumab and alemtuzumab. Natalizumab is considered one of the most potent treatments for relapse prevention. However, the high risk of progressive multifocal leukoencephalopathy (PML), which is caused by JC virus infection in the brain, tempers the more widespread use of this agent; nevertheless, JC virus antibody tests have helped to stratify the risk of PML. Alemtuzumab, which also has a considerable side effect profile, is likewise highly efficacious. Ocrelizumab, a monoclonal antibody to CD20 on B cells, is a highly effective agent for MS that is likely to be approved soon by the FDA. MS is a major contributor to healthcare costs and it is critical that healthcare providers be aware of the availability and benefits of DMTs. It is imperative that prompt and adequate treatment be established on diagnosis. Changes in therapy should be considered when there is evidence of disease activity as well as accumulation of disability or safety or tolerability concerns.
多发性硬化症（MS）是一种中枢神经系统（CNS）的自身免疫性脱髓鞘疾病。它主要影响年轻女性，是年轻成年人致残的最常见原因之一。MS的特征是由于炎症、脱髓鞘和轴突丢失，在中枢神经系统中形成白质病变。60多年来，治疗一直是神经学研究的重点。一些疾病修正疗法（DMTs）已经问世，使MS成为一种可治疗的疾病。这些化合物针对MS中的炎症反应。它们通过降低复发几率、减少中枢神经系统MRI上出现新病变的几率以及减缓残疾累积来发挥作用。首批用于MS的药物是干扰素-β和醋酸格拉替雷。它们通过不同机制调节炎症反应，在此简要讨论。此后出现了更新的药物，显著改变了MS治疗的格局。这些药物包括口服制剂芬戈莫德、富马酸二甲酯和特立氟胺。其他经美国食品药品监督管理局（FDA）批准的二线和三线药物包括那他珠单抗和阿仑单抗。那他珠单抗被认为是预防复发最有效的治疗方法之一。然而，由大脑中JC病毒感染引起的进行性多灶性白质脑病（PML）的高风险限制了该药物的更广泛使用；尽管如此，JC病毒抗体检测有助于对PML风险进行分层。同样具有相当多副作用的阿仑单抗也非常有效。奥瑞珠单抗是一种针对B细胞上CD20的单克隆抗体，是一种治疗MS的高效药物，很可能很快获得FDA批准。MS是医疗保健成本的主要贡献因素，医疗保健提供者了解DMTs的可用性和益处至关重要。确诊后必须立即建立及时且充分的治疗。当有疾病活动证据以及出现残疾累积、安全或耐受性问题时，应考虑改变治疗方案。
