Hardinger Karen L, Brennan Daniel C
Karen L Hardinger, Department of Pharmacy Practice and Administration, University of Missouri-Kansas City, Kansas City, MO 64108, United States.
World J Transplant. 2013 Dec 24;3(4):68-77. doi: 10.5500/wjt.v3.i4.68.
Excellent outcomes have been achieved in the field of renal transplantation. A significant reduction in acute rejection has been attained at many renal transplant centers using contemporary immunosuppressive, consisting of an induction agent, a calcineurin inhibitor, an antiproliferative agent plus or minus a corticosteroid. Despite improvements with these regimens, chronic allograft injury and adverse events still persist. The perfect immunosuppressive regimen would limit or eliminate calcineurin inhibitors and/or corticosteroid toxicity while providing enhanced allograft outcomes. Potential improvements to the calcineurin inhibitor class include a prolonged release tacrolimus formulation and voclosporin, a cyclosporine analog. Belatacept has shown promise as an agent to replace calcineurin inhibitors. A novel, fully-human anti-CD40 monoclonal antibody, ASKP1240, is currently enrolling patients in phase 2 trials with calcineurin minimization and avoidance regimens. Another future goal of transplant immunosuppression is effective and safe treatment of allograft rejection. Novel treatments for antibody mediated rejection include bortezomib and eculizumab. Several investigational agents are no longer being pursed in transplantation including the induction agents, efalizumab and alefacept, and maintenance agents, sotrastaurin and tofacitinib. The purpose of this review is to consolidate the published evidence of the effectiveness and safety of investigational immunosuppressive agents in renal transplant recipients.
肾移植领域已取得了出色的成果。许多肾移植中心通过使用当代免疫抑制方案,包括一种诱导剂、一种钙调神经磷酸酶抑制剂、一种抗增殖剂加或不加一种皮质类固醇,使急性排斥反应显著减少。尽管这些方案有了改进,但慢性移植物损伤和不良事件仍然存在。理想的免疫抑制方案应能限制或消除钙调神经磷酸酶抑制剂和/或皮质类固醇的毒性,同时提高移植物的疗效。钙调神经磷酸酶抑制剂类药物的潜在改进包括缓释他克莫司制剂和环孢素类似物voclosporin。贝拉西普已显示出有望作为替代钙调神经磷酸酶抑制剂的药物。一种新型的全人源抗CD40单克隆抗体ASKP1240目前正在招募患者进行2期试验,采用尽量减少和避免使用钙调神经磷酸酶的方案。移植免疫抑制的另一个未来目标是对移植物排斥反应进行有效且安全的治疗。抗体介导排斥反应的新型治疗方法包括硼替佐米和依库珠单抗。几种研究性药物已不再用于移植领域,包括诱导剂依法利珠单抗和阿法赛特,以及维持药物索拉司他丁和托法替布。本综述的目的是汇总已发表的关于研究性免疫抑制药物在肾移植受者中的有效性和安全性的证据。