Hartung Hans-Peter, Aktas Orhan, Boyko Alexey N
Department of Neurology and Center for Neuropsychiatry, Medical Faculty, Heinrich-Heine University, Germany
Department of Neurology and Center for Neuropsychiatry, Medical Faculty, Heinrich-Heine University, Germany.
Mult Scler. 2015 Jan;21(1):22-34. doi: 10.1177/1352458514549398. Epub 2014 Oct 24.
Alemtuzumab is a humanized monoclonal antibody directed against CD52 to deplete circulating T and B lymphocytes; lymphocyte depletion is followed by a distinctive pattern of T- and B-cell repopulation, changing the balance of the immune system. This review reports the efficacy and safety findings of the phase 2 CAMMS223 trial and the phase 3 CARE-MS I and II trials investigating alemtuzumab for the treatment of active relapsing-remitting MS. Alemtuzumab, administered intravenously, was shown to improve relapse rate versus subcutaneous interferon beta-1a in patients who were treatment-naive (CAMMS223 and CARE-MS I) or had relapsed on prior therapy (CARE-MS II), and to reduce sustained accumulation of disability (CAMMS223 and CARE-MS II). Important adverse events were infusion-associated reactions, serious infections and autoimmune events. A safety monitoring program allowed for early detection and management of autoimmune events. Recommendations for the monitoring of adverse events are made. Alemtuzumab's mechanism of action, pharmacodynamics and opportunities for future research are discussed.
阿仑单抗是一种靶向CD52的人源化单克隆抗体，用于清除循环中的T淋巴细胞和B淋巴细胞；淋巴细胞清除后会出现独特的T细胞和B细胞再填充模式，从而改变免疫系统的平衡。本综述报告了2期CAMMS223试验以及3期CARE-MS I和II试验的疗效和安全性结果，这些试验研究了阿仑单抗治疗活动性复发缓解型多发性硬化症（MS）的效果。在未接受过治疗的患者（CAMMS223和CARE-MS I）或既往治疗后复发的患者（CARE-MS II）中，静脉注射阿仑单抗与皮下注射干扰素β-1a相比，复发率更低，且能减少残疾的持续累积（CAMMS223和CARE-MS II）。重要的不良事件包括输液相关反应、严重感染和自身免疫事件。一个安全监测项目能够早期发现并处理自身免疫事件。文中给出了不良事件监测的建议。还讨论了阿仑单抗的作用机制、药效学以及未来的研究方向。
