Two-year outcomes in de novo renal transplant recipients receiving everolimus-facilitated calcineurin inhibitor reduction regimen from the TRANSFORM study
Two-year outcomes in de novo renal transplant recipients receiving everolimus-facilitated calcineurin inhibitor reduction regimen from the TRANSFORM study
复制标题
DOI：
10.1111/ajt.15480
复制
发表时间：
2019-07-01
影响因子：
8.8
通讯作者：
Pascual, Julio
中科院分区：
文献类型：
--
作者：
Berger, Stefan P.;Sommerer, Claudia;Pascual, Julio
TRANSFORM（基于依维莫司的方案的移植疗效和安全性结局）是一项为期24个月的前瞻性开放标签试验，在2037例初次肾移植受者中进行，在移植后24小时内随机（1：1）接受依维莫司（EVR）联合低暴露钙调磷酸酶抑制剂（EVR + rCNI）或霉酚酸酯联合标准暴露CNI。与先前报道的12个月研究结果一致，EVR + rCNI方案在治疗后活检证实的急性排斥反应（tBPAR）或估计肾小球滤过率（eGFR）mL/min/1.73 m2的主要终点方面的非劣效性在第24个月达到（47.9% vs 43.7%;差异= 4.2%; 95%置信区间=-0.3，8.7; P = 0.006）。两组的平均eGFR稳定至第24个月（52.6 vs 54.9 mL/min/1.73 m2）。在治疗患者中，EVR + rCNI组新发供体特异性抗体（dnDSA）的发生率较低（12.3% vs 17.6%）。尽管EVR + rCNI组因不良事件导致的停药率较高（27.2% vs 15.0%），但巨细胞病毒（2.8% vs 13.5%）和BK病毒（5.8% vs 10.3%）感染率较低。即使在D+/R-高危组中，EVR + rCNI组的巨细胞病毒感染率也显著降低（P < .0001）。总之，EVR + rCNI方案提供了相当的疗效和移植物功能，tBPAR和dnDSA发生率较低，病毒感染发生率相对于标准治疗显著降低，长达24个月。Clinicaltrials.gov编号：NCT 01950819。
TRANSFORM (TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen) was a 24-month, prospective, open-label trial in 2037 de novo renal transplant recipients randomized (1:1) within 24 hours of transplantation to receive everolimus (EVR) with reduced-exposure calcineurin inhibitor (EVR + rCNI) or mycophenolate with standard-exposure CNI. Consistent with previously reported 12-month findings, noninferiority of the EVR + rCNI regimen for the primary endpoint of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) mL/min per 1.73 m(2) was achieved at month 24 (47.9% vs 43.7%; difference = 4.2%; 95% confidence interval = -0.3, 8.7; P = .006). Mean eGFR was stable up to month 24 (52.6 vs 54.9 mL/min per 1.73 m(2)) in both arms. The incidence of de novo donor-specific antibodies (dnDSA) was lower in the EVR + rCNI arm (12.3% vs 17.6%) among on-treatment patients. Although discontinuation rates due to adverse events were higher with EVR + rCNI (27.2% vs 15.0%), rates of cytomegalovirus (2.8% vs 13.5%) and BK virus (5.8% vs 10.3%) infections were lower. Cytomegalovirus infection rates were significantly lower with EVR + rCNI even in the D+/R- high-risk group (P < .0001). In conclusion, the EVR + rCNI regimen offers comparable efficacy and graft function with low tBPAR and dnDSA rates and significantly lower incidence of viral infections relative to standard-of-care up to 24 months. Clinicaltrials.gov number: NCT01950819.