Gupta Gaurav, Womer Karl L
Division of Nephrology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Drug Des Devel Ther. 2010 Dec 1;4:375-82. doi: 10.2147/DDDT.S10432.
The last several decades have witnessed a substantial decrease in the incidence of acute allograft rejection following kidney transplantation, although commensurate improvements in long-term graft function have not been realized. As a result, the primary focus of new immunosuppressive drug development has expanded to include ease of use and improved side effect profile, including reduced nephrotoxicity, in addition to the more traditional goal of improved short-term outcomes. A number of novel drugs are currently under investigation in Phase I, II, or III clinical trials, primarily to replace the nephrotoxic but highly effective calcineurin inhibitors. Belatacept is a humanized antibody that inhibits T cell costimulation and has shown encouraging results in multiple Phase II and III trials. This article reviews the mechanism of action of belatacept, as well as published and preliminary results of the Phase I-III clinical trials involving this novel immunosuppressive agent.
在过去几十年间，肾移植后急性同种异体移植排斥反应的发生率显著下降，尽管长期移植肾功能并未相应改善。因此，新型免疫抑制药物研发的主要重点已扩大到包括使用便利性和改善副作用，除了改善短期疗效这一更为传统的目标外，还包括降低肾毒性。目前有多种新型药物正处于I期、II期或III期临床试验阶段，主要是为了替代具有肾毒性但高效的钙调神经磷酸酶抑制剂。贝拉西普是一种抑制T细胞共刺激的人源化抗体，已在多项II期和III期试验中显示出令人鼓舞的结果。本文综述了贝拉西普的作用机制，以及涉及这种新型免疫抑制剂的I - III期临床试验的已发表和初步结果。
