Menge Til, Stüve Olaf, Kieseier Bernd C, Hartung Hans-Peter
From the Department of Neurology and Center for Neuropsychiatry (T.M., O.S., B.C.K., H.-P.H.), Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; and the Department of Neurology and Neurotherapeutics (O.S.), University of Texas Southwestern Medical Center at Dallas.
Neurology. 2014 Jul 1;83(1):87-97. doi: 10.1212/WNL.0000000000000540. Epub 2014 Jun 11.
Our understanding of the pathogenesis of multiple sclerosis has increased considerably, leading to the development of novel therapeutic approaches and compounds. Several agents have undergone clinical testing and have recently received market authorization or are being evaluated for approval. Alemtuzumab is a humanized monoclonal antibody that rapidly depletes CD52+ cells of the lymphoid lineage from peripheral blood, but spares lymphoid precursor cells. Clinical efficacy and safety data from clinical phase II and III trials-all using interferon-β-1a as active comparator-are summarized and placed in perspective. This review further analyzes the differential reconstitution of T and B cells as a potential mode of action and the pathogenic link to treatment-emergent secondary autoimmune conditions. Given recent positive opinions by regulatory agencies, this new drug will be positioned for the treatment of active relapsing-remitting multiple sclerosis and enlarge our therapeutic armamentarium.
我们对多发性硬化症发病机制的理解有了显著提高，这促使了新型治疗方法和化合物的研发。有几种药物已经进行了临床试验，最近已获得市场授权，或者正在接受审批评估。阿仑单抗是一种人源化单克隆抗体，它能迅速清除外周血中淋巴谱系的CD52+细胞，但保留淋巴前体细胞。总结并综合分析了以干扰素-β-1a作为活性对照的II期和III期临床试验的临床疗效和安全性数据。本综述进一步分析了T细胞和B细胞的差异重建作为一种潜在的作用模式，以及与治疗后出现的继发性自身免疫性疾病的致病联系。鉴于监管机构最近给出的积极意见，这种新药将用于治疗活动性复发缓解型多发性硬化症，并扩大我们的治疗手段。
