Two-dose daclizumab regimen in simultaneous kidney-pancreas transplant recipients: Primary endpoint analysis of a multicenter, randomized study
Two-dose daclizumab regimen in simultaneous kidney-pancreas transplant recipients: Primary endpoint analysis of a multicenter, randomized study
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DOI：
10.1097/01.tp.0000062838.38351.2a
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发表时间：
2003-04-27
期刊：
影响因子：
6.2
通讯作者：
Hodge, E
中科院分区：
文献类型：
--
作者：
Stratta, RJ;Alloway, RR;Hodge, E
背景肾胰联合移植（SKPT）受者的最佳免疫抑制方案存在争议。本研究确定了接受他克莫司、吗替麦考酚酯和类固醇的SKPT受者中两种daclizumab给药方案与无抗体诱导相比的安全性和有效性。这项前瞻性、多中心、随机、开放标签研究共入组了297例SKPT患者。患者被随机分为三组：达克珠单抗1 mg/kg/剂，每14天一次，共5剂（组I，n=107），达克珠单抗2 mg/kg/剂，每14天一次，共2剂（组II，n=112），无抗体诱导（组III，n=78）。所有患者均接受他克莫司、霉酚酸酯和类固醇作为维持免疫抑制剂。各组的人口统计学和移植特征相似。在6个月时，三组之间的患者、肾脏和胰腺移植物存活率没有差异。在第I、II和III组中，6个月时肾脏或胰腺移植物排斥反应的概率分别为21%、17%和32%（P=0.042）。第1组至肾脏或胰腺首次急性排斥反应的中位时间为23天，第II组为44天，第III组为20天（第I组与第II组，P=0.078;第II组与第III组，P=0.016）。6个月时，I、II和III组的精算无事件生存率（无急性排斥反应、同种异体移植物丢失或死亡）分别为66%、77%和56%（I组与III组，P=0.119; II组与III组，P=0.002）。各组之间严重不良事件（包括感染并发症）的发生率无差异。所有三组在6个月时均表现出良好的肾脏和胰腺功能。与无抗体诱导相比，Daclizumab可安全有效地降低SKPT受者的急性排斥反应发生率。此外，达克珠单抗的两剂量方案（在第0天和第14天2 mg/kg）与标准的五剂量方案相比是有利的。
Background. Controversy exists about the optimal immunosuppressive regimen in simultaneous kidney-pancreas transplant (SKPT) recipients. This study determined the safety and efficacy of two dosing regimens of daclizumab compared with no antibody induction in SKPT recipients receiving tacrolimus, mycophenolate mofetil, and steroids.Methods. A total of 297 SKPT patients were enrolled in this prospective, multicenter, randomized, open-label study. The patients were randomized into three groups: daclizumab 1 mg/kg per dose every 14 days for five doses (group I, n=107), daclizumab 2 mg/kg per dose every 14 days for two doses (group II, n=112), and no antibody induction (group III, n=78). All patients received tacrolimus, mycophenolate mofetil, and steroids as maintenance immunosuppression.Results. Demographic and transplant characteristics were similar among the groups. At 6 months, there were no differences in patient, kidney, and pancreas graft survival rates among the three groups. The probability of either kidney or pancreas allograft rejection at 6 months was 21%, 17%, and 32% in groups I, II, and III, respectively (P=0.042). The median time to first acute rejection of either the kidney or pancreas was 23 days in group 1, 44 days in group II, and 20 days in group III (group I vs. II, P=0.078; group II vs. III, P=0.016). At 6 months, the actuarial event-free survival (no acute rejection, allograft loss, or death) rates were 66%, 77%, and 56% in groups I, II, and III, respectively (group I vs. III, P=0.119; group II vs. III, P=0.002). There were no differences in the incidence of serious adverse events including infectious complications among the groups. All three groups demonstrate excellent kidney and pancreas function at 6 months.Conclusions. Daclizumab is safe and effective in reducing the incidence of acute rejection in SKPT recipients compared with no antibody induction. Moreover, the two-dose regimen of daclizumab (2 mg/kg on days 0 and 14) compares favorably with the standard five-dose regimen.