Hersh Carrie M, Cohen Jeffrey A
Mellen Center for Multiple Sclerosis Treatment & Research, Neurological Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Immunotherapy. 2014;6(3):249-59. doi: 10.2217/imt.14.7.
Alemtuzumab, a humanized monoclonal antibody that targets CD52, was recently approved in the EU and Canada for the treatment of patients with active relapsing-remitting multiple sclerosis. Alemtuzumab induces rapid depletion of circulating B- and T-lymphocytes followed by repopulation that leads to a distinctive lymphocyte profile, including an increased proportion of regulatory T-lymphocytes and memory B- and T-lymphocytes. In early open-label studies, alemtuzumab treatment reduced the number of clinical relapses and new MRI lesions in participants with secondary progressive MS. However, most participants had continued worsening of disability, which led to the evaluation of alemtuzumab in patients with early stages of disease in the Genzyme (MA, USA)-sponsored clinical development program in MS. In one Phase II and two Phase III trials, alemtuzumab reduced the number of clinical relapses versus the active comparator, subcutaneous IFN-β-1a, in treatment-naive and treatment-experienced participants with relapsing-remitting multiple sclerosis. Two of these trials showed reduction in risk of confirmed worsening of disability, and all showed reduction in cerebral atrophy. Safety issues include infusion reactions that are mitigated by pretreatment with corticosteroids in addition to symptomatic management with antihistamines; mild to moderate infections; and autoimmune adverse events. In this context, post-marketing risk mitigation strategies will be needed so that potential adverse events can be identified and managed early and effectively.
阿仑单抗是一种靶向CD52的人源化单克隆抗体，最近在欧盟和加拿大被批准用于治疗活动性复发缓解型多发性硬化症患者。阿仑单抗可迅速消耗循环中的B淋巴细胞和T淋巴细胞，随后细胞重新增殖，导致独特的淋巴细胞谱，包括调节性T淋巴细胞以及记忆B淋巴细胞和T淋巴细胞的比例增加。在早期开放标签研究中，阿仑单抗治疗减少了继发进展型多发性硬化症参与者的临床复发次数和新的磁共振成像（MRI）病灶数量。然而，大多数参与者的残疾状况持续恶化，这促使在基因泰克公司（美国马萨诸塞州）赞助的多发性硬化症临床开发项目中，对疾病早期患者使用阿仑单抗进行评估。在一项II期试验和两项III期试验中，对于初治和有治疗经验的复发缓解型多发性硬化症参与者，与活性对照皮下注射干扰素β-1a相比，阿仑单抗减少了临床复发次数。其中两项试验显示确诊的残疾恶化风险降低，所有试验均显示脑萎缩减少。安全问题包括输注反应（可通过在使用抗组胺药进行症状处理的基础上，预先使用皮质类固醇来减轻）、轻度至中度感染以及自身免疫性不良事件。在这种情况下，将需要采取上市后风险缓解策略，以便能够早期有效地识别和管理潜在的不良事件。
