Transplantation. 1998 Jan 27;65(2):235-41.
Mycophenolate mofetil (MMF) significantly reduces the incidence of acute allograft rejection in renal transplant patients. The effect of adding MMF to the immunosuppressive regimen of patients with established rejection is unknown. The purpose of the current study was to compare the safety and efficacy of the addition of MMF to the treatment regimen of an early first acute cellular rejection.
The study was a double-blind, double-dummy controlled clinical trial of 221 renal transplant recipients experiencing the first biopsy-proven rejection within 6 months of transplant performed at 15 U.S. and Canadian centers. A total of 113 patients received MMF (1.5 g twice daily) and intravenous corticosteroids, and 108 patients received azathioprine (AZA) (1-2 mg/kg/day) and intravenous corticosteroids. The intravenous corticosteroids in each group consisted of 5 mg/kg/day for 5 days followed by an oral steroid taper. End points for the study were the first use of antilymphocyte therapy, the number of courses of antirejection therapy given during the first 6 months, and graft and patient survival at 1 year.
At 6 months, 16.8% of the MMF-treated patients and 41.7% of the AZA-treated patients required at least one course of antilymphocyte therapy (P < 0.0001). The number of patients requiring full courses of antirejection therapy for the treatment of rejection was less in the MMF-treated group (24.8%) versus the AZA-treated group (58.3%) (P < 0.0001). The proportion of patients with the use of antilymphocyte therapy or treatment failure during the first 6 months was 29.2% vs. 51.9% (P=0.0006) in the MMF versus the AZA groups, respectively. By 1 year after enrollment, 10 patients (8.9%) in the MMF-treated group lost their graft or died versus 16 patients (14.8%) in the AZA-treated group. More patients in the MMF group withdrew because of an adverse event: 20 patients (17.7%) compared with 11 AZA-treated patients (10.2%).
MMF administered in combination with pulse corticosteroids significantly decreases the subsequent use of antilymphocyte therapy in the treatment of acute renal allograft rejection. In addition to being a safe and effective prophylactic agent, MMF added to steroids improves the rate of reversal of acute rejection episodes.
霉酚酸酯（MMF）可显著降低肾移植患者急性移植排斥反应的发生率。在已发生排斥反应的患者免疫抑制方案中添加MMF的效果尚不清楚。本研究的目的是比较在早期首次急性细胞排斥反应治疗方案中添加MMF的安全性和有效性。
该研究是一项双盲、双模拟对照临床试验，纳入了221例肾移植受者，这些患者在美国和加拿大的15个中心接受移植，且在移植后6个月内首次经活检证实发生排斥反应。总共113例患者接受MMF（每日2次，每次1.5 g）和静脉注射皮质类固醇，108例患者接受硫唑嘌呤（AZA）（1 - 2 mg/kg/天）和静脉注射皮质类固醇。每组的静脉注射皮质类固醇均为5 mg/kg/天，持续5天，随后口服逐渐减量的类固醇。研究的终点是首次使用抗淋巴细胞治疗、前6个月内给予的抗排斥治疗疗程数以及1年时的移植物和患者生存率。
6个月时，接受MMF治疗的患者中有16.8%，接受AZA治疗的患者中有41.7%需要至少一个疗程的抗淋巴细胞治疗（P < 0.0001）。MMF治疗组中因排斥反应需要接受完整抗排斥治疗疗程的患者数量（24.8%）少于AZA治疗组（58.3%）（P < 0.0001）。MMF组和AZA组在前6个月内使用抗淋巴细胞治疗或治疗失败的患者比例分别为29.2%和51.9%（P = 0.0006）。入组后1年时，MMF治疗组有10例患者（8.9%）失去移植物或死亡，而AZA治疗组有16例患者（14.8%）。MMF组因不良事件退出的患者更多：20例患者（17.7%），而AZA治疗组有11例患者（10.2%）。
MMF联合脉冲皮质类固醇给药可显著减少急性肾移植排斥反应治疗中后续抗淋巴细胞治疗的使用。除了是一种安全有效的预防药物外，在类固醇治疗中添加MMF可提高急性排斥反应发作的逆转率。
