Until recently, in the pathogenesis of Multiple Sclerosis (MS), the contribution of B cells has been largely underestimated, and the disease was considered a T-cell-mediated disorder. However, newer evidence shows that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and through the cross regulation of T-helper cells. As B cells express the surface molecule CD20 at all points of differentiation, it provides a specific target for monoclonal antibodies, and the development and clinical testing of anti-CD20 antibody treatments for MS have been successful. After some observations, some small clinical trials found positive effects for the first anti-CD20 therapeutic rituximab in MS; newer agents have been specifically evaluated, resulting in the development of ocrelizumab and ofatumumab. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, was approved in March 2017 by the Food and Drug Administration (FDA) and is also the first proven therapy to reduce disability progression in primary progressive MS. This is particularly significant considering that disease-modifying treatment options are few for both primary and secondary progressive MS. Ofatumumab, a fully human anti-CD20 monoclonal antibody, that binds a distinct epitope, has been further investigated in phase 3 trials for relapsing forms of MS. In this review, we discuss in detail these two anti-CD20 agents and their advent for treatment of MS.

中文翻译：

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治疗多发性硬化症的抗 CD20 药物：聚焦 Ocrelizumab 和 Ofatumumab


直到最近，在多发性硬化症 (MS) 的发病机制中，B 细胞的贡献在很大程度上被低估，并且该疾病被认为是 T 细胞介导的疾病。然而，新的证据表明，B 细胞通过抗原驱动的自身抗体反应和 T 辅助细胞的交叉调节，在 MS 的发病机制中发挥着至关重要的作用。由于 B 细胞在所有分化点都表达表面分子 CD20，因此它为单克隆抗体提供了特定靶标，针对 MS 的抗 CD20 抗体治疗的开发和临床测试已取得成功。经过一些观察，一些小型临床试验发现第一个抗CD20治疗药物利妥昔单抗对MS有积极效果；新药经过专门评估，导致了 ocrelizumab 和 ofatumumab 的开发。 Ocrelizumab 是一种人源化抗 CD20 单克隆抗体，于 2017 年 3 月获得美国食品和药物管理局 (FDA) 批准，也是第一个经过验证的可减少原发进展型 MS 残疾进展的疗法。考虑到原发性和继发性进展性多发性硬化症的疾病缓解治疗选择很少，这一点尤其重要。 Ofatumumab 是一种全人源抗 CD20 单克隆抗体，可结合不同的表位，已在针对复发型多发性硬化症的 3 期试验中进行了进一步研究。在这篇综述中，我们详细讨论了这两种抗 CD20 药物及其治疗多发性硬化症的出现。