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The potential role for ocrelizumab in the treatment of multiple sclerosis: current evidence and future prospects

机译:ocrelizumab在多发性硬化症治疗中的潜在作用:当前证据和未来前景

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B cells play a central role in the pathogenesis in multiple sclerosis (MS), being involved in the activation of proinflammatory T cells, secretion of proinflammatory cytokines, and production of autoantibodies directed against myelin. Hence, the usage of B-cell-depleting monoclonal antibodies as therapy for autoimmune diseases including MS lay near at hand. Rituximab was the first therapeutic B-cell-depleting chimeric monoclonal antibody to be used successfully in MS. Ocrelizumab, a second-generation humanized anti-CD20 antibody, was explored in a large phase II, randomized, placebo-controlled multicentre trial in patients with relapsing–remitting disease. Compared with placebo, two doses of ocrelizumab (600 and 2000 mg on days 1 and 15) showed a pronounced effect on disease activity seen in magnetic resonance imaging (MRI) as gadolinium-enhanced lesions (89% and 96% relative reduction, both p Other anti-CD20 monoclonal antibodies have been tested as treatments for MS, including ofatumumab that has shown beneficial results in placebo-controlled phase II trials in patients with relapsing–remitting MS. Ocrelizumab is now in phase III development for the treatment of relapsing–remitting MS, as well as primary progressive MS, and the results of ongoing clinical trials are eagerly awaited and will determine the place of ocrelizumab in the armamentarium of MS therapies.
机译:B细胞在多发性硬化症(MS)的发病机理中起着关键作用,参与促炎性T细胞的活化,促炎性细胞因子的分泌以及针对髓磷脂的自身抗体的产生。因此,即将耗尽B细胞的单克隆抗体作为自身免疫性疾病(包括MS)的疗法。利妥昔单抗是第一种成功用于MS的治疗性B细胞耗竭嵌合单克隆抗体。 Ocrelizumab是第二代人源化抗CD20抗体,在一项II期随机,安慰剂对照的多中心大型临床试验中进行了研究,该试验用于复发性疾病。与安慰剂相比,两种剂量的ocrelizumab(在第1天和第15天分别为600和2000 mg)对g增强的病变(在磁共振成像(MRI)中可见)对疾病活动具有显着影响(相对减少89%和96%,两者均p其他抗CD20单克隆抗体也已作为MS治疗方法进行了测试,包括ofatumumab在复发缓解型MS患者的安慰剂对照II期临床试验中显示了有益的结果,Ocrelizumab目前正处于复发缓解型MS III期开发中。急切地等待着MS以及主要的进行性MS,以及正在进行的临床试验的结果,这些结果将确定ocrelizumab在MS治疗的武器库中的位置。

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