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靶向 B 细胞以修饰多发性硬化症、NMOSD 和 MOGA:第 1 部分。

Targeting B Cells to Modify MS, NMOSD, and MOGAD: Part 1.

机构信息

From the Department of Neurology (J.G., O.A., P.A., H.-P.H.), University Hospital, Medical Faculty Heinrich-Heine-University, Düsseldorf, Germany; Department of Neurology (J.M.), Palacky University, Olomouc, Czech Republic; Department of Neurology (M.B., H.-P.H.), Brain and Mind Centre, Department of Neurology, University of Sydney, New South Wales, Australia; and UCSF Weill Institute of Neurosciences (S.S.Z.), Department of Neurology, University of California at San Francisco.

出版信息

Neurol Neuroimmunol Neuroinflamm. 2020 Dec 16;8(1). doi: 10.1212/NXI.0000000000000918. Print 2021 Jan.

Abstract

Ocrelizumab, rituximab, ofatumumab, ublituximab, inebilizumab, and evobrutinib are immunotherapies that target various B cell-related proteins. Most of these treatments have proven efficacy in relapsing and progressive forms of MS and neuromyelitis optica spectrum disease (NMOSD), or are in advanced stages of clinical development. Currently, ocrelizumab, ofatumumab, and inebilizumab are licensed for treatment of MS and NMOSD, respectively. This review focuses on the current state of knowledge about the role of B lymphocytes in immune-mediated pathophysiology and its implications for the mode of action. To understand the significance of this breakthrough in the context of the current MS therapeutic armamentarium, this review more closely examines the clinical development of CD20 depletion and the pioneering contribution of rituximab. Phase 3 and the recently published postmarketing studies will be highlighted to better understand the relevant efficacy data and safety aspects of long-term B-cell depletion.

摘要

奥瑞珠单抗、利妥昔单抗、奥法妥木单抗、乌布雷替尤单抗、伊奈利珠单抗和埃沃妥珠单抗是靶向各种 B 细胞相关蛋白的免疫疗法。这些治疗方法中的大多数已被证明对复发型和进行型多发性硬化症和视神经脊髓炎谱系疾病(NMOSD)有效,或处于临床开发的后期阶段。目前,奥瑞珠单抗、奥法妥木单抗和伊奈利珠单抗分别被批准用于治疗多发性硬化症和 NMOSD。本综述重点介绍了 B 淋巴细胞在免疫介导的病理生理学中的作用及其对作用模式的影响的现有知识状况。为了在当前多发性硬化症治疗武器库的背景下理解这一突破的意义,本综述更仔细地研究了 CD20 耗竭的临床开发和利妥昔单抗的开创性贡献。将重点介绍 3 期和最近发表的上市后研究,以更好地了解长期 B 细胞耗竭的相关疗效数据和安全性方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ff/8063619/c487fb4c824d/NEURIMMINFL2020034306f1.jpg

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