Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation.

Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1.73 m² at post-transplant month 12 using a 10% noninferiority margin.

Results In the intent-to-treat population (everolimus n=1022, MPA n=1015), the primary end point incidence was 48.2% (493) with everolimus and 45.1% (457) with MPA (difference 3.2%; 95% confidence interval, −1.3% to 7.6%). Similar between-treatment differences in incidence were observed in the subgroups of patients who received tacrolimus or cyclosporine. Treated biopsy-proven acute rejection, graft loss, or death at post-transplant month 12 occurred in 14.9% and 12.5% of patients treated with everolimus and MPA, respectively (difference 2.3%; 95% confidence interval, −1.7% to 6.4%). De novo donor-specific antibody incidence at 12 months and antibody-mediated rejection rate did not differ between arms. Cytomegalovirus (3.6% versus 13.3%) and BK virus infections (4.3% versus 8.0%) were less frequent in the everolimus arm than in the MPA arm. Overall, 23.0% and 11.9% of patients treated with everolimus and MPA, respectively, discontinued the study drug because of adverse events.

Conclusions In kidney transplant recipients at mild-to-moderate immunologic risk, everolimus was noninferior to MPA for a binary composite end point assessing immunosuppressive efficacy and preservation of graft function.

背景依维莫司允许减少钙调神经磷酸酶抑制剂（CNI）的暴露，但是需要证实该治疗在肾移植后的疗效和安全性。

方法在一项多中心非劣效性试验中，我们将2037例从头开始接受肾脏移植的患者随机分组，与诱导治疗和皮质类固醇激素联合使用依维莫司联合低暴露CNI（依维莫司组）或霉酚酸（MPA）联合标准暴露CNI（MPA组） ）。主要终点是经过活检证实的急性排斥反应或eGFR <50 ml / min（1.73 m ² /移植后第12个月时eGFR <50 ml / min），非劣效性为10％。

结果在意向性治疗人群（依维莫司n = 1022，MPA n = 1015）中，依维莫司的主要终点发生率为48.2％（493），MPA的主要终点发生率为45.1％（457）（差异3.2％; 95％置信度）区间-1.3％至7.6％）。在接受他克莫司或环孢霉素治疗的患者亚组中观察到相似的治疗间发生率差异。经治疗的活检证明在依维莫司和MPA治疗的患者中，分别在14.9％和12.5％的患者中发生了经活检证实的急性排斥，移植物丢失或死亡（差异为2.3％； 95％的置信区间为-1.7％至6.4％ ）。从头开始供体特异性抗体在12个月时的发生率和抗体介导的排斥率在两组之间没有差异。依维莫司组中的巨细胞病毒（3.6％对13.3％）和BK病毒感染（4.3％对8.0％）的发生率低于MPA组。总体而言，依维莫司和MPA治疗的患者中分别有23.0％和11.9％因不良事件而中止研究药物。

结论在轻度至中度免疫风险的肾脏移植受者中，依维莫司在评估免疫抑制功效和保留移植物功能方面的二元复合终点不逊于MPA。