Division of Nephrology and Kidney Transplantation, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Room NA523, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Clin Pharmacokinet. 2018 Feb;57(2):191-207. doi: 10.1007/s40262-017-0573-x.
Alemtuzumab is a humanized monoclonal antibody against CD52 and causes depletion of T and B lymphocytes, monocytes, and NK cells. Alemtuzumab is registered for the treatment of multiple sclerosis (MS) and is also used in chronic lymphocytic leukemia (CLL). Alemtuzumab is used off-label in kidney transplantation as induction and anti-rejection therapy. The objective of this review is to present a review of the pharmacokinetics, pharmacodynamics, and use of alemtuzumab in kidney transplantation. A systematic literature search was conducted using Ovid Medline, Embase, and Cochrane Central Register of controlled trials. No pharmacokinetic or dose-finding studies of alemtuzumab have been performed in kidney transplantation. Although such studies were conducted in patients with CLL and MS, these findings cannot be directly extrapolated to transplant recipients, because CLL patients have a much higher load of CD52-positive cells and, therefore, target-mediated clearance will differ between these two indications. Alemtuzumab used as induction therapy in kidney transplantation results in a lower incidence of acute rejection compared to basiliximab therapy and comparable results as compared with rabbit anti-thymocyte globulin (rATG). Alemtuzumab used as anti-rejection therapy results in a comparable graft survival rate compared with rATG, although infusion-related side effects appear to be less. There is a need for pharmacokinetic and dose-finding studies of alemtuzumab in kidney transplant recipients to establish the optimal balance between efficacy and toxicity. Furthermore, randomized controlled trials with sufficient follow-up are necessary to provide further evidence for the treatment of severe kidney transplant rejection.
阿仑单抗是一种针对 CD52 的人源化单克隆抗体，可导致 T 和 B 淋巴细胞、单核细胞和 NK 细胞耗竭。阿仑单抗已注册用于治疗多发性硬化症（MS），也用于慢性淋巴细胞白血病（CLL）。阿仑单抗在肾移植中作为诱导和抗排斥治疗的适应证外使用。本综述的目的是介绍阿仑单抗在肾移植中的药代动力学、药效学和应用。使用 Ovid Medline、Embase 和 Cochrane 对照试验中心注册库进行了系统的文献检索。尚未在肾移植中进行阿仑单抗的药代动力学或剂量发现研究。尽管在 CLL 和 MS 患者中进行了这些研究，但这些发现不能直接外推到移植受者，因为 CLL 患者的 CD52 阳性细胞负荷要高得多，因此这两种适应证之间的靶向介导清除将有所不同。与巴利昔单抗治疗相比，阿仑单抗用于肾移植诱导治疗可降低急性排斥反应的发生率，与兔抗胸腺细胞球蛋白（rATG）的结果相当。阿仑单抗用于抗排斥治疗的移植物存活率与 rATG 相当，尽管输注相关副作用似乎较少。需要在肾移植受者中进行阿仑单抗的药代动力学和剂量发现研究，以确定疗效和毒性之间的最佳平衡。此外，还需要进行具有足够随访的随机对照试验，以提供进一步的证据来治疗严重的肾移植排斥反应。
