Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Department of Neurosciences, Multiple Sclerosis Center of the Veneto Region, University Hospital-School of Medicine, Padua, Italy.
Neurotherapeutics. 2022 Jul;19(4):1216-1228. doi: 10.1007/s13311-022-01252-5. Epub 2022 Jun 6.
Multiple sclerosis (MS) is a chronic inflammatory, demyelinating, and neurodegenerative disease affecting the central nervous system, often characterized by the accumulation of irreversible clinical disability over time. In recent years, there has been a dramatic evolution in several key concepts of MS treatment. The demonstration of the effects of ocrelizumab, a selective monoclonal antibody against CD20 B cells, has significantly modified our knowledge of the immune-pathophysiology of MS and has provided a new therapeutic target for relapsing and progressive MS patients. Emerging findings suggest that, besides its strong anti-inflammatory activity, ocrelizumab may limit disability progression and may exert beneficial effects on cognitive function, fatigue, and quality of life of MS patients. The significant reductions of the rate of global and regional brain atrophy and of serum neurofilament light chain levels, which were found to be partially independent of overt inflammatory activity, suggest that this treatment may also limit neuro-axonal damage. By discussing the most recent evidence regarding the effects of ocrelizumab on clinical measures as well as on magnetic resonance imaging and fluid biomarkers, this review summarizes current knowledge on the possible mechanisms underlying the effects of ocrelizumab in limiting MS progression and neurodegeneration.
多发性硬化症（MS）是一种影响中枢神经系统的慢性炎症、脱髓鞘和神经退行性疾病，通常表现为随着时间的推移不可逆临床残疾的累积。近年来，MS 治疗的几个关键概念发生了重大演变。针对 CD20 B 细胞的选择性单克隆抗体奥瑞珠单抗的疗效证明，显著改变了我们对 MS 免疫发病机制的认识，并为复发型和进展型 MS 患者提供了新的治疗靶点。新出现的研究结果表明，奥瑞珠单抗除了具有强大的抗炎活性外，还可能限制残疾进展，并对 MS 患者的认知功能、疲劳和生活质量产生有益影响。发现脑容积和血清神经丝轻链水平的全球和区域萎缩率显著降低，且部分与明显的炎症活动无关，这表明该治疗方法也可能限制神经轴突损伤。本文通过讨论奥瑞珠单抗对临床指标以及磁共振成像和液体生物标志物的最新影响证据，总结了奥瑞珠单抗在限制 MS 进展和神经退行性变方面的可能作用机制的现有知识。
