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多发性硬化症抗CD20疗法的分子与药理学特性的临床视角

Clinical Perspectives on the Molecular and Pharmacological Attributes of Anti-CD20 Therapies for Multiple Sclerosis.

作者信息

Bar-Or Amit, O'Brien Susan M, Sweeney Michael L, Fox Edward J, Cohen Jeffrey A

机构信息

Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA.

出版信息

CNS Drugs. 2021 Sep;35(9):985-997. doi: 10.1007/s40263-021-00843-8. Epub 2021 Aug 9.

Abstract

Anti-CD20 therapies have demonstrated considerable efficacy in the treatment of relapsing multiple sclerosis, constituting a high-efficacy treatment approach for reducing relapse risk and mitigating disability progression. These therapies have been shown to strongly deplete circulating B cells and small subsets of CD3+ CD4 and CD8 T cells that express low levels of CD20. While the clinical profiles of the various anti-CD20 monoclonal antibodies used in treating multiple sclerosis are well-described in the literature, greater understanding of the implications of their distinct molecular and pharmacological attributes is needed. In this review, we focus on four anti-CD20 monoclonal antibodies-rituximab, ocrelizumab, ofatumumab, and ublituximab-that are currently used, approved, or in late-stage clinical development for the treatment of multiple sclerosis. We provide clinical perspectives on the potential implications of differences in molecular structures, target epitopes, dosing regimens, mechanisms and impact on B-cell depletion and reconstitution, immunogenicity, administration-related reactions, and infection risks.

摘要

抗CD20疗法在复发型多发性硬化症的治疗中已显示出显著疗效,是降低复发风险和减缓残疾进展的一种高效治疗方法。这些疗法已被证明能强烈清除循环B细胞以及表达低水平CD20的CD3+ CD4和CD8 T细胞小亚群。虽然用于治疗多发性硬化症的各种抗CD20单克隆抗体的临床概况在文献中有详尽描述,但仍需要更深入了解它们独特的分子和药理学特性所带来的影响。在本综述中,我们重点关注四种目前用于、已获批或处于多发性硬化症治疗后期临床开发阶段的抗CD20单克隆抗体——利妥昔单抗、奥瑞珠单抗、奥法木单抗和乌布利妥昔单抗。我们从临床角度探讨了分子结构、靶抗原表位、给药方案、作用机制以及对B细胞清除和重建、免疫原性、给药相关反应和感染风险的影响等方面差异的潜在意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3a3/8408056/7b9cfe30e9f1/40263_2021_843_Fig1_HTML.jpg

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