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抗CD20 B细胞耗竭药物在多发性硬化症中的疗效与安全性比较

Comparison of the Efficacy and Safety of Anti-CD20 B Cells Depleting Drugs in Multiple Sclerosis.

作者信息

Cotchett Kelly R, Dittel Bonnie N, Obeidat Ahmed Z

机构信息

Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI; Versiti Blood Research Institute, Milwaukee, WI.

Department of Neurology, Medical College of Wisconsin, Milwaukee, WI.

出版信息

Mult Scler Relat Disord. 2021 Apr;49:102787. doi: 10.1016/j.msard.2021.102787. Epub 2021 Jan 22.

Abstract

Rituximab, ocrelizumab, ofatumumab and ublituximab are disease modifying therapies (DMT) currently used in the treatment of multiple sclerosis (MS) or are in advanced stages of clinical trials. These monoclonal antibodies deplete B cells by targeting the cell surface protein CD20. This review highlights the similarities and major differences between the four agents. We summarize data from various clinical trials of each of these therapeutics and discuss their efficacy and safety. Additional considerations regarding the route of administration and cost are presented. Among the four therapeutics, only ocrelizumab is approved for primary progressive (PP) MS. Infusion/injection related reactions (IRRs) are the most common adverse events associated with all four therapeutics. In phase III trials of ocrelizumab and ofatumumab, the incidence of IRRs was lower with ofatumumab. Ofatumumab is unique among the four therapeutics due to its availability as a subcutaneous injection (SQ). Although SQ administration may be appealing for some patients it may raise concerns regarding medication compliance among physicians. Phase II trials studying ublituximab for the treatment of RMS yielded promising results. Phase III trials are currently comparing the efficacy of ublituximab to teriflunomide.

摘要

利妥昔单抗、奥瑞珠单抗、奥法木单抗和乌布利昔单抗是目前用于治疗多发性硬化症(MS)或正处于临床试验后期阶段的疾病修正疗法(DMT)。这些单克隆抗体通过靶向细胞表面蛋白CD20来消耗B细胞。本综述重点介绍了这四种药物之间的异同。我们总结了每种疗法的各种临床试验数据,并讨论了它们的疗效和安全性。还介绍了关于给药途径和成本的其他注意事项。在这四种疗法中,只有奥瑞珠单抗被批准用于原发性进行性(PP)MS。输注/注射相关反应(IRR)是与所有四种疗法相关的最常见不良事件。在奥瑞珠单抗和奥法木单抗的III期试验中,奥法木单抗的IRR发生率较低。奥法木单抗在这四种疗法中独具特色,因为它可以皮下注射(SQ)。虽然皮下注射给药对一些患者可能有吸引力,但可能会引起医生对用药依从性的担忧。研究乌布利昔单抗治疗复发型多发性硬化症(RMS)的II期试验取得了有前景的结果。III期试验目前正在比较乌布利昔单抗与特立氟胺的疗效。

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