Department of Neurology, Medical University of Vienna, Vienna, Austria.
Department of Neurology, Palacky University Olomouc, Olomouc, Czech Republic.
Neurotherapeutics. 2022 Apr;19(3):753-773. doi: 10.1007/s13311-022-01224-9. Epub 2022 Apr 4.
Monoclonal antibodies have become a mainstay in the treatment of patients with relapsing multiple sclerosis (RMS) and provide some benefit to patients with primary progressive MS. They are highly precise by specifically targeting molecules displayed on cells involved in distinct immune mechanisms of MS pathophysiology. They not only differ in the target antigen they recognize but also by the mode of action that generates their therapeutic effect. Natalizumab, an [Formula: see text][Formula: see text] integrin antagonist, works via binding to cell surface receptors, blocking the interaction with their ligands and, in that way, preventing the migration of leukocytes across the blood-brain barrier. On the other hand, the anti-CD52 monoclonal antibody alemtuzumab and the anti-CD20 monoclonal antibodies rituximab, ocrelizumab, ofatumumab, and ublituximab work via eliminating selected pathogenic cell populations. However, potential adverse effects may be serious and can necessitate treatment discontinuation. Most importantly, those are the risk for (opportunistic) infections, but also secondary autoimmune diseases or malignancies. Monoclonal antibodies also carry the risk of infusion/injection-related reactions, primarily in early phases of treatment. By careful patient selection and monitoring during therapy, the occurrence of these potentially serious adverse effects can be minimized. Monoclonal antibodies are characterized by a relatively long pharmacologic half-life and pharmacodynamic effects, which provides advantages such as permitting infrequent dosing, but also creates disadvantages regarding vaccination and family planning. This review presents an overview of currently available monoclonal antibodies for the treatment of RMS, including their mechanism of action, efficacy and safety profile. Furthermore, we provide practical recommendations for risk management, vaccination, and family planning.
单克隆抗体已成为治疗复发性多发性硬化症（RMS）患者的主要手段，并为原发性进展性多发性硬化症患者提供了一定的益处。它们通过特异性靶向多发性硬化症病理生理学中涉及不同免疫机制的细胞上显示的分子，具有高度的精确性。它们不仅在识别的靶抗原上有所不同，而且在产生治疗效果的作用方式上也有所不同。那他珠单抗是一种[化学式：见正文][化学式：见正文]整合素拮抗剂，通过与细胞表面受体结合发挥作用，阻断与配体的相互作用，从而防止白细胞穿过血脑屏障迁移。另一方面，抗 CD52 单克隆抗体阿仑单抗和抗 CD20 单克隆抗体利妥昔单抗、奥瑞珠单抗、奥法妥珠单抗和乌利昔单抗通过消除选定的致病细胞群发挥作用。然而，潜在的不良反应可能很严重，可能需要停止治疗。最重要的是，这些是（机会性）感染的风险，但也有继发性自身免疫性疾病或恶性肿瘤的风险。单克隆抗体也有输注/注射相关反应的风险，主要发生在治疗的早期阶段。通过在治疗期间仔细选择和监测患者，可以最大限度地减少这些潜在严重不良反应的发生。单克隆抗体的特点是具有相对较长的药代动力学半衰期和药效学效应，这提供了允许较少频率给药等优势，但也在疫苗接种和计划生育方面带来了劣势。本综述介绍了目前可用于治疗 RMS 的单克隆抗体，包括它们的作用机制、疗效和安全性概况。此外，我们还提供了有关风险管理、疫苗接种和计划生育的实用建议。
