Hospital do Rim e Hipertensão, São Paulo, Brazil.
Am J Transplant. 2010 Jun;10(6):1401-13. doi: 10.1111/j.1600-6143.2010.03129.x. Epub 2010 Apr 28.
Everolimus allows calcineurin-inhibitor reduction without loss of efficacy and may improve renal-transplant outcomes. In a 24-month, open-label study, 833 de novo renal-transplant recipients were randomized to everolimus 1.5 or 3.0 mg/day (target troughs 3-8 and 6-12 ng/mL, respectively) with reduced-exposure CsA, or mycophenolic acid (MPA) 1.44 g/day plus standard-exposure CsA. Patients received basiliximab +/- corticosteroids. The primary endpoint was composite efficacy failure (treated biopsy-proven acute rejection, graft loss, death or loss to follow-up) and the main safety endpoint was renal function (estimated glomerular filtration rate [eGFR], by Modification of Diet in Renal Disease [MDRD]) at Month 12 (last-observation-carried-forward analyses). Month 12 efficacy failure rates were noninferior in the everolimus 1.5 mg (25.3%) and 3.0 mg (21.9%) versus MPA (24.2%) groups. Mean eGFR at Month 12 was noninferior in the everolimus groups versus the MPA group (54.6 and 51.3 vs 52.2 mL/min/1.73 m(2) in the everolimus 1.5 mg, 3.0 mg and MPA groups, respectively; 95% confidence intervals for everolimus 1.5 mg and 3.0 mg vs MPA: -1.7, 6.4 and -5.0, 3.2, respectively). The overall incidence of adverse events was comparable between groups. The use of everolimus with progressive reduction in CsA exposure, up to 60% at 1 year, resulted in similar efficacy and renal function compared with standard-exposure CsA plus MPA.
依维莫司可减少钙调磷酸酶抑制剂用量而不降低疗效,并可能改善肾移植结局。在一项为期 24 个月、开放性标签的研究中,833 例初发肾移植受者被随机分配至依维莫司 1.5 或 3.0mg/天(目标谷浓度分别为 3-8ng/ml 和 6-12ng/ml)联合低剂量环孢素 A 或霉酚酸(MPA)1.44g/天联合标准剂量环孢素 A。所有患者均接受巴利昔单抗联合或不联合皮质激素治疗。主要终点为复合疗效失败(治疗后经活检证实的急性排斥反应、移植物丢失、死亡或失访),主要安全性终点为肾功能(通过改良肾脏病膳食研究法[MDRD]估算肾小球滤过率[eGFR]),评估时间点为第 12 个月(最后观察值结转分析)。依维莫司 1.5mg 组(25.3%)和 3.0mg 组(21.9%)的 12 个月疗效失败率与 MPA 组(24.2%)相比均不劣效。12 个月时,依维莫司组的平均 eGFR 与 MPA 组相比非劣效(依维莫司 1.5mg、3.0mg 和 MPA 组分别为 54.6、51.3 和 52.2mL/min/1.73m2;依维莫司 1.5mg 和 3.0mg 组与 MPA 组的 95%置信区间分别为-1.7,6.4 和-5.0,3.2)。各组间不良事件总体发生率相当。依维莫司联合逐步减少环孢素 A 暴露(1 年时减至 60%)的治疗方案与标准剂量环孢素 A 联合 MPA 的疗效和肾功能相当。