Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary.
Transpl Int. 2012 May;25(5):592-602. doi: 10.1111/j.1432-2277.2012.01465.x. Epub 2012 Mar 26.
There is increasing interest in tacrolimus-minimization regimens. ASSET was an open-label, randomized, 12-month study of everolimus plus tacrolimus in de-novo renal-transplant recipients. Everolimus trough targets were 3-8 ng/ml throughout the study. Tacrolimus trough targets were 4-7 ng/ml during the first 3 months and 1.5-3 ng/ml (n = 107) or 4-7 ng/ml (n = 117) from Month 4. All patients received basiliximab induction and corticosteroids. The primary objective was to demonstrate superior estimated glomerular filtration rate (eGFR; MDRD-4) at Month 12 in the tacrolimus 1.5-3 ng/ml versus the 4-7 ng/ml group. Secondary endpoints included incidence of biopsy-proven acute rejection (BPAR; Months 4-12) and serious adverse events (SAEs; Months 0-12). Statistical significance was not achieved for the primary endpoint (mean eGFR: 57.1 vs. 51.7 ml/min/1.73 m(2)), potentially due to overlapping of achieved tacrolimus exposure levels (Month 12 mean ± SD, tacrolimus 1.5-3 ng/ml: 3.4 ± 1.4; tacrolimus 4-7 ng/ml: 5.5 ± 2.0 ng/ml). BPAR (months 4-12) and SAE rates were comparable between groups (2.7% vs. 1.1% and 58.7% vs. 51.3%; respectively). Everolimus-facilitated tacrolimus minimization, to levels lower than previously investigated, achieved good renal function, low BPAR and graft-loss rates, and an acceptable safety profile in renal transplantation over 12 months although statistically superior renal function of the 1.5-3 ng/ml tacrolimus group was not achieved.
越来越多的人对他克莫司最小化方案感兴趣。ASSET 是一项为期 12 个月的开放性标签、随机研究,比较了依维莫司联合他克莫司用于初治肾移植受者。整个研究期间,依维莫司谷浓度目标为 3-8ng/ml。在前 3 个月,他克莫司谷浓度目标为 4-7ng/ml,从第 4 个月起,他克莫司谷浓度目标为 1.5-3ng/ml(n=107)或 4-7ng/ml(n=117)。所有患者均接受巴利昔单抗诱导和皮质激素治疗。主要目标是在第 12 个月时,1.5-3ng/ml 他克莫司组的估算肾小球滤过率(eGFR;MDRD-4)优于 4-7ng/ml 组。次要终点包括活检证实的急性排斥反应(BPAR;第 4-12 个月)和严重不良事件(SAE;第 0-12 个月)的发生率。主要终点未达到统计学意义(平均 eGFR:57.1 与 51.7ml/min/1.73m2),可能是由于实现的他克莫司暴露水平重叠(第 12 个月的平均±SD,1.5-3ng/ml 他克莫司组:3.4±1.4ng/ml;4-7ng/ml 他克莫司组:5.5±2.0ng/ml)。两组之间的 BPAR(第 4-12 个月)和 SAE 发生率相似(分别为 2.7%与 1.1%和 58.7%与 51.3%)。依维莫司辅助的他克莫司最小化方案,将他克莫司浓度降至此前研究未曾探索过的水平,在 12 个月的肾移植中,可实现良好的肾功能、低 BPAR 和移植物丢失率,并具有可接受的安全性,但未达到 1.5-3ng/ml 他克莫司组的统计学上更好的肾功能。