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抗 CD20 疗法在多发性硬化症中的应用:从病理学到临床。

Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic.

机构信息

Department of Neurology, Hôpital de Hautepierre, Clinical Investigation Center, Institut National de la Santé et de la Recherche Médicale (INSERM), Strasbourg, France.

Fédération de Médecine Translationelle, Institut National de la Santé et de la Recherche Médicale (INSERM), Strasbourg, France.

出版信息

Front Immunol. 2023 Mar 23;14:1004795. doi: 10.3389/fimmu.2023.1004795. eCollection 2023.

Abstract

The immune system plays a significant role in multiple sclerosis. While MS was historically thought to be T cell-mediated, multiple pieces of evidence now support the view that B cells are essential players in multiple sclerosis pathogenic processes. High-efficacy disease-modifying therapies that target the immune system have emerged over the past two decades. Anti-CD20 monoclonal antibodies selectively deplete CD20+ B and CD20+ T cells and efficiently suppress inflammatory disease activity. These monotherapies prevent relapses, reduce new or active magnetic resonance imaging brain lesions, and lessen disability progression in patients with relapsing multiple sclerosis. Rituximab, ocrelizumab, and ofatumumab are currently used in clinical practice, while phase III clinical trials for ublituximab have been recently completed. In this review, we compare the four anti-CD20 antibodies in terms of their mechanisms of action, routes of administration, immunological targets, and pharmacokinetic properties. A deeper understanding of the individual properties of these molecules in relation to their efficacy and safety profiles is critical for their use in clinical practice.

摘要

免疫系统在多发性硬化症中起着重要作用。虽然多发性硬化症在历史上被认为是 T 细胞介导的,但现在有多项证据支持 B 细胞是多发性硬化症发病机制中不可或缺的参与者的观点。过去二十年中出现了多种针对免疫系统的高效疾病修正治疗方法。抗 CD20 单克隆抗体选择性地消耗 CD20+B 和 CD20+T 细胞,并有效地抑制炎症性疾病活动。这些单药疗法可预防复发,减少新的或活跃的磁共振成像脑损伤,并减缓复发型多发性硬化症患者的残疾进展。利妥昔单抗、奥瑞珠单抗和奥法妥木单抗目前已在临床实践中使用,而乌布雷昔单抗的 III 期临床试验最近已完成。在这篇综述中,我们比较了这四种抗 CD20 抗体在作用机制、给药途径、免疫靶点和药代动力学特性方面的差异。深入了解这些分子在疗效和安全性方面的个体特性对于它们在临床实践中的应用至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1f5/10076836/dd50c50a2c7d/fimmu-14-1004795-g001.jpg

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