MS Comprehensive Care Center, Stony Brook University, Department of Neurology , Stony Brook, NY 11794-8121 , USA +1 631 444 8188 ; +1 631 444 1474 ;
Expert Opin Biol Ther. 2014 Jan;14(1):127-35. doi: 10.1517/14712598.2014.866084. Epub 2013 Dec 2.
Alemtuzumab is a humanized IgG1 kappa monoclonal antibody approved for treatment of B-cell chronic lymphocytic leukemia. This cytolytic antibody is directed against CD52 and depletes lymphocytes, with monocytes, macrophages, natural killer cells and a subpopulation of granulocytes being affected to a much lesser degree. Alemtuzumab is currently under review to treat relapsing multiple sclerosis (MS) in the United States, based on positive Phase II and Phase III trials in both treatment-naïve and treated relapsing MS patients. There was excellent efficacy in suppressing both clinical and neuroimaging disease activities. In these trials, the comparator arm was not placebo, but high dose frequently dosed subcutaneous interferon beta 1a. Alemtuzumab has recently been approved by the European authorities for active relapsing MS, in essence as a first-line agent. It produces long-standing effects, consistent with an induction agent. Efficacy will have to be weighed against risk of adverse effects, which include autoimmune disorders and infection. Alemtuzumab joins an increasingly crowded market, and will add to the complexity of treating MS.
This review will discuss alemtuzumab as a therapy for MS, reviewing PubMed for clinical trials, publications and presentations at international meetings. It will focus on a United States market perspective.
Alemtuzumab offers induction strategy for very active relapsing MS patients who have failed conventional therapy, and possibly selected treatment-naive patients. Alemtuzumab use is likely to be restricted to specialized MS centers, with long-term monitoring to determine the true risk for adverse effects.
阿仑单抗是一种人源化 IgG1κ单克隆抗体，获批用于治疗 B 细胞慢性淋巴细胞白血病。这种细胞毒性抗体针对 CD52，可耗竭淋巴细胞，单核细胞、巨噬细胞、自然杀伤细胞和亚群粒细胞受到的影响要小得多。阿仑单抗目前正在美国接受审查，以治疗复发性多发性硬化症（MS），基于在初治和复发性 MS 患者中的阳性 II 期和 III 期试验。它在抑制临床和神经影像学疾病活动方面均有出色的疗效。在这些试验中，对照组不是安慰剂，而是高剂量、频繁皮下注射的干扰素 β1a。阿仑单抗最近已被欧洲当局批准用于活动性复发性 MS，实际上是一线药物。它产生长期效果，与诱导剂一致。疗效必须与不良反应风险相权衡，包括自身免疫性疾病和感染。阿仑单抗加入了一个日益拥挤的市场，将增加 MS 的治疗复杂性。
本综述将讨论阿仑单抗作为 MS 的治疗方法，在 PubMed 上搜索临床试验、出版物和国际会议的演讲。它将重点关注美国市场的角度。
阿仑单抗为常规治疗失败的非常活跃的复发性 MS 患者，以及可能选择的初治患者提供诱导策略。阿仑单抗的使用可能仅限于专门的 MS 中心，需要进行长期监测以确定不良反应的真正风险。
