Ofatumumab: A Novel Anti-CD20 Monoclonal Antibody for Multiple Sclerosis: A Review of Clinical Considerations

William T. Barham, Kathryn M. Dillman, Joseph D. Hebert, Christian K. Kerut, Rachel J. Klapper, Shahab Ahmadzadeh, Sahar Shekoohi, Elyse M. Cornett, Alan D. Kaye
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Abstract

Multiple sclerosis (MS), an autoimmune central nervous system disease responsible for significant morbidity and mortality worldwide, remains imperfectly understood and treated clinically. Recent advances in treating MS have come in the form of new immunomodulatory agents. Of these, anti-CD20 monoclonal antibodies (mAbs) have exhibited particular promise in treating relapsing–remitting multiple sclerosis (RRMS), the early stage of the disease where the adaptive immune system facilitates an autoimmune attack against myelin. The depletion of CD20 positive B cells in patients with RRMS has been associated with decreased symptoms, disease progression, and lesions on MRI, as well as a more favorable side effect profile relative to other immunomodulatory therapies for MS. Of the anti-CD20 mAbs available for use in MS, one of the newest is ofatumumab, a fully human anti-CD20 IgG1κ, sold under the trade name Kesimpta. The present investigation reviews the efficacy and safety of ofatumumab for MS, highlighting the role that B cells play in the initial inflammatory stage of MS and their depletion in decreasing clinical symptoms, T2-enhancing MRI lesions, and progression to the immune-independent phase of MS.

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奥法图穆单抗治疗多发性硬化症的新型抗 CD20 单克隆抗体:临床考虑因素综述
多发性硬化症(MS)是一种自身免疫性中枢神经系统疾病,在全球范围内造成了严重的发病率和死亡率,但人们对这种疾病的认识和临床治疗仍不完善。治疗多发性硬化症的最新进展是采用了新的免疫调节药物。其中,抗 CD20 单克隆抗体(mAbs)在治疗复发-缓解型多发性硬化症(RRMS)方面显示出特别的前景,RRMS 是疾病的早期阶段,在这一阶段,适应性免疫系统促进了对髓鞘的自身免疫攻击。在 RRMS 患者中消耗 CD20 阳性 B 细胞与症状减轻、疾病进展和核磁共振成像上的病灶有关,而且相对于其他多发性硬化症免疫调节疗法而言,CD20 阳性 B 细胞的副作用更小。在可用于多发性硬化症的抗CD20 mAbs中,最新的一种是ofatumumab,它是一种全人源抗CD20 IgG1κ,商品名为Kesimpta。本研究回顾了多发性硬化症用药ofatumumab的疗效和安全性,强调了B细胞在多发性硬化症初期炎症阶段所起的作用,以及B细胞耗竭对减少临床症状、T2增强MRI病灶和多发性硬化症进展到免疫依赖期所起的作用。
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