Wiseman L R, Faulds D
Adis International Limited, Mairangi Bay, Auckland, New Zealand.
Drugs. 1999 Dec;58(6):1029-42. doi: 10.2165/00003495-199958060-00006.
The humanised monoclonal antibody daclizumab is an immunosuppressive agent that reduces acute rejection in renal transplant recipients. It is specific for the alpha subunit (Tac/CD25) of the interleukin-2 (IL-2) receptor on activated T cells and achieves immunosuppression by competitive antagonism of IL-2-induced T cell proliferation. Daclizumab has advantages over murine antibodies to the IL-2 receptor, including improved effector function, a low potential for immunogenicity and long elimination half-life. When added to standard cyclosporin-based immunosuppressive therapy with or without azathioprine, daclizumab (1 mg/kg prior to surgery and once every 2 weeks thereafter for a total of 5 doses) significantly reduced the 6-month rate of acute rejection compared with placebo in 2 phase III studies. The mean number of rejection episodes was significantly reduced and the time to first acute rejection significantly increased in daclizumab versus placebo recipients. Patient survival at 1 year after transplantation was significantly higher with daclizumab than placebo in 1 study and showed a trend in favour of the drug in the other study. The 1-year graft survival rate tended to be greater in daclizumab than in placebo recipients in both studies, In a phase II study, acute rejection rates in patients treated with both daclizumab and mycophenolate mofetil (plus standard cyclosporin-based immunosuppression) were lower than those achieved with mycophenolate mofetil alone. Preliminary results indicate that daclizumab is also a useful agent in paediatric renal transplant recipients. Further investigation of the efficacy and tolerability of the drug in this patient group is clearly warranted. Daclizumab does not increase the incidence of adverse events when added to standard cyclosporin-based therapy. The incidence of opportunistic infections, lymphoproliferative disorders and malignancies was not increased above that seen with placebo.
Although the effects of daclizumab on long term graft and patient survival require further investigation, available data indicate that daclizumab is an important advance in renal transplant immunosuppression, reducing acute graft rejection without affecting the tolerability of standard cyclosporin-based immunosuppression.
人源化单克隆抗体达利珠单抗是一种免疫抑制剂，可降低肾移植受者的急性排斥反应。它对活化T细胞上白细胞介素-2（IL-2）受体的α亚基（Tac/CD25）具有特异性，并通过竞争性拮抗IL-2诱导的T细胞增殖来实现免疫抑制。与抗IL-2受体的鼠源抗体相比，达利珠单抗具有优势，包括改善效应功能、低免疫原性潜力和长消除半衰期。在两项III期研究中，当与或不与硫唑嘌呤联合应用于基于环孢素的标准免疫抑制治疗时，达利珠单抗（术前1mg/kg，此后每2周一次，共5剂）与安慰剂相比，显著降低了6个月时的急性排斥反应发生率。与安慰剂接受者相比，达利珠单抗接受者的排斥反应发作平均次数显著减少，首次急性排斥反应时间显著延长。在一项研究中，达利珠单抗治疗的患者移植后1年的生存率显著高于安慰剂，在另一项研究中显示出有利于该药物的趋势。在两项研究中，达利珠单抗治疗的患者1年移植物生存率均倾向于高于安慰剂接受者。在一项II期研究中，接受达利珠单抗和霉酚酸酯（加基于环孢素的标准免疫抑制）治疗的患者的急性排斥反应率低于单独使用霉酚酸酯的患者。初步结果表明，达利珠单抗在儿科肾移植受者中也是一种有用的药物。显然有必要进一步研究该药物在该患者群体中的疗效和耐受性。当添加到基于环孢素的标准治疗中时，达利珠单抗不会增加不良事件的发生率。机会性感染、淋巴增殖性疾病和恶性肿瘤的发生率没有高于安慰剂组。
尽管达利珠单抗对长期移植物和患者生存的影响需要进一步研究，但现有数据表明，达利珠单抗是肾移植免疫抑制的一项重要进展，可降低急性移植物排斥反应，而不影响基于环孢素的标准免疫抑制的耐受性。
