Qazi Y, Shaffer D, Kaplan B, Kim D Y, Luan F L, Peddi V R, Shihab F, Tomlanovich S, Yilmaz S, McCague K, Patel D, Mulgaonkar S
University of Southern California, Los Angeles, CA.
Division of Kidney and Pancreas Transplantation, Vanderbilt University Medical Center, Nashville, TN.
Am J Transplant. 2017 May;17(5):1358-1369. doi: 10.1111/ajt.14090. Epub 2017 Jan 4.
In this 12-month, multicenter, randomized, open-label, noninferiority study, de novo renal transplant recipients (RTxRs) were randomized (1:1) to receive everolimus plus low-dose tacrolimus (EVR+LTac) or mycophenolate mofetil plus standard-dose Tac (MMF+STac) with induction therapy (basiliximab or rabbit anti-thymocyte globulin). Noninferiority of composite efficacy failure rate (treated biopsy-proven acute rejection [tBPAR]/graft loss/death/loss to follow-up) in EVR+LTac versus MMF+STac was missed by 1.4%, considering the noninferiority margin of 10% (24.6% vs. 20.4%; 4.2% [-3.0, 11.4]). Incidence of tBPAR (19.1% vs. 11.2%; p < 0.05) was significantly higher, while graft loss (1.3% vs. 3.9%; p < 0.05) and composite of graft loss/death/lost to follow-up (6.1% vs. 10.5%, p = 0.05) were significantly lower in EVR+LTac versus MMF+STac groups, respectively. Mean estimated glomerular filtration rate was similar between EVR+LTac and MMF+STac groups (63.1 [22.0] vs. 63.1 [19.5] mL/min/1.73 m ) and safety was comparable. In conclusion, EVR+LTac missed noninferiority versus MMF+STac based on the 10% noninferiority margin. Further studies evaluating optimal immunosuppression for improved efficacy will guide appropriate dosing and target levels of EVR and LTac in RTxRs.
在这项为期12个月的多中心、随机、开放标签、非劣效性研究中，初发肾移植受者（RTxRs）被随机分组（1:1），接受依维莫司加低剂量他克莫司（EVR+LTac）或霉酚酸酯加标准剂量他克莫司（MMF+STac）并进行诱导治疗（巴利昔单抗或兔抗胸腺细胞球蛋白）。考虑到10%的非劣效性界值（24.6%对20.4%；4.2%[-3.0, 11.4]），EVR+LTac组与MMF+STac组相比，复合疗效失败率（经活检证实的治疗性急性排斥反应[tBPAR]/移植肾丢失/死亡/失访）未达到非劣效性，相差1.4%。EVR+LTac组的tBPAR发生率显著更高（19.1%对11.2%；p<0.05），而移植肾丢失率（1.3%对3.9%；p<0.05）以及移植肾丢失/死亡/失访的复合发生率（6.1%对10.5%，p=0.05）在EVR+LTac组与MMF+STac组中分别显著更低。EVR+LTac组和MMF+STac组的平均估计肾小球滤过率相似（63.1[22.0]对63.1[19.5]mL/min/1.73 m²），安全性相当。总之，基于10%的非劣效性界值，EVR+LTac与MMF+STac相比未达到非劣效性。进一步评估优化免疫抑制以提高疗效的研究将指导RTxRs中EVR和LTac的合适剂量及目标水平。
