An open-label, randomized trial indicates that everolimus with tacrolimus or cyclosporine is comparable to standard immunosuppression in de novo kidney transplant patients
An open-label, randomized trial indicates that everolimus with tacrolimus or cyclosporine is comparable to standard immunosuppression in de novo kidney transplant patients
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DOI：
10.1016/j.kint.2019.01.041
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发表时间：
2019-07-01
影响因子：
19.6
通讯作者：
Witzke, Oliver
中科院分区：
文献类型：
--
作者：
Sommerer, Claudia;Suwelack, Barbara;Witzke, Oliver
这是一项在初治肾移植患者中进行的随机化试验（ATHENA研究），旨在比较依维莫司与霉酚酸（MPA），两组中他克莫司暴露相似，或依维莫司与他克莫司或环孢素（CsA）合并使用，在一个稳定人群中。在这项为期12个月、多中心、开放标签研究中，初治肾移植受者被随机分配至依维莫司+他克莫司（EVR/TAC）、依维莫司+CsA（EVR/CsA）或MPA+他克莫司（MPA/TAC）组，两组的他克莫司暴露量相似。在338例患者的符合方案人群中评估的主要终点（第12个月时估计的肾小球滤过率[eGFR]）的非劣效性未显示EVR/TAC或EVR/CsA与MPA/TAC相比。在TAC水平在方案规定范围内的123例患者中，两组之间的eGFR结局相当。移植后1至12个月期间，EVR/TAC或EVR/CsA组与MPA/TAC组的eGFR平均增幅（事后分析）相似。治疗失败（活检证实的急性排斥反应、移植物丢失或死亡）的发生率在EVR/TAC中不显著，但在EVR/CsA与MPA/TAC中显著。本研究中大多数活检证实的急性排斥反应事件分级为轻度（BANFF IA）。两组间蛋白尿无差异。巨细胞病毒和BK病毒感染在MPA/TAC中明显更常见。因此，依维莫司与TAC或CsA在新发肾移植患者中显示出与MPA/TAC相当的疗效。未显示预先规定的肾功能非劣效性，但eGFR从第1个月至第12个月的平均增幅与MPA/TAC相当。
This is a randomized trial (ATHENA study) in de novo kidney transplant patients to compare everolimus versus mycophenolic acid (MPA) with similar tacrolimus exposure in both groups, or everolimus with concomitant tacrolimus or cyclosporine (CsA), in an unselected population. In this 12-month, multicenter, open-label study, de novo kidney transplant recipients were randomized to everolimus with tacrolimus (EVR/TAC), everolimus with CsA (EVR/CsA) or MPA with tacrolimus (MPA/TAC), with similar tacrolimus exposure in both groups. Non-inferiority of the primary end point (estimated glomerular filtration rate [eGFR] at month 12), assessed in the per-protocol population of 338 patients, was not shown for EVR/TAC or EVR/CsA versus MPA/TAC. In 123 patients with TAC levels within the protocol-specified range, eGFR outcomes were comparable between groups. The mean increase in eGFR during months 1 to 12 post-transplant, analyzed post hoc, was similar with EVR/TAC or EVR/CsA versus MPA/TAC. The incidence of treatment failure (biopsy proven acute rejection, graft loss or death) was not significant for EVR/ TAC but significant for EVR/CsA versus MPA/TAC. Most biopsy-proven acute rejection events in this study were graded mild (BANFF IA). There were no differences in proteinuria between groups. Cytomegalovirus and BK virus infection were significantly more frequent with MPA/TAC. Thus, everolimus with TAC or CsA showed comparable efficacy to MPA/TAC in de novo kidney transplant patients. Non-inferiority of renal function, when pre-specified, was not shown, but the mean increase in eGFR from month 1 to 12 was comparable to MPA/TAC.