心脏移植受者中霉酚酸酯的随机活性对照试验。霉酚酸酯研究人员。

A randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients. Mycophenolate Mofetil Investigators.

作者信息

Kobashigawa J, Miller L, Renlund D, Mentzer R, Alderman E, Bourge R, Costanzo M, Eisen H, Dureau G, Ratkovec R, Hummel M, Ipe D, Johnson J, Keogh A, Mamelok R, Mancini D, Smart F, Valantine H

机构信息

University of California, Los Angeles, USA.

出版信息

Transplantation. 1998 Aug 27;66(4):507-15. doi: 10.1097/00007890-199808270-00016.

DOI:10.1097/00007890-199808270-00016

PMID:9734496

Abstract

BACKGROUND

After heart transplantation, 1-year and 5-year survival rates are 79% and 63%, respectively, with rejection, infection, and allograft coronary artery disease accounting for the majority of deaths. Mycophenolate mofetil (MMF), an inhibitor of the de novo pathway for purine biosynthesis, decreases rejection in animals and in human renal transplantation.

METHODS

In a double-blind, active-controlled trial, 28 centers randomized 650 patients undergoing their first heart transplant to receive MMF (3000 mg/day) or azathioprine (1.5-3 mg/kg/day), in addition to cyclosporine and corticosteroids. Rejection and survival data were obtained for 6 and 12 months, respectively. Because 11% of the patients withdrew before receiving study drug, data were analyzed on all randomized patients (enrolled patients) and on patients who received study medications (treated patients).

RESULTS

Survival and rejection were similar in enrolled patients (MMF, n=327; azathioprine, n=323). In treated patients (MMF, n=289; azathioprine, n=289), the MMF group compared with the azathioprine group was associated with significant reduction in mortality at 1 year (18 [6.2%] versus 33 deaths [11.4%]; P=0.031) and a significant reduction in the requirement for rejection treatment (65.7% versus 73.7%; P=0.026). There was a trend for fewer MMF patients to have > or = grade 3A rejection (45.0% versus 52.9%; P=0.055) or require the murine monoclonal anti-CD3 antibody or antithymocyte globulin (15.2% versus 21.1%; P=0.061). Opportunistic infections, mostly herpes simplex, were more common in the MMF group (53.3% versus 43.6%; P=0.025).

CONCLUSIONS

Substitution of MMF for azathioprine may reduce mortality and rejection in the first year after cardiac transplantation.

摘要

背景

心脏移植后，1年和5年生存率分别为79%和63%，死亡主要原因是排斥反应、感染和移植心脏冠状动脉疾病。霉酚酸酯（MMF）是嘌呤生物合成从头合成途径的抑制剂，可降低动物和人类肾移植中的排斥反应。

方法

在一项双盲、活性药物对照试验中，28个中心将650例首次接受心脏移植的患者随机分为两组，除环孢素和皮质类固醇外，分别接受MMF（3000毫克/天）或硫唑嘌呤（1.5 - 3毫克/千克/天）治疗。分别在6个月和12个月时获取排斥反应和生存数据。由于11%的患者在接受研究药物前退出，因此对所有随机分组患者（入组患者）和接受研究药物治疗的患者（治疗患者）的数据进行了分析。

结果

入组患者（MMF组，n = 327；硫唑嘌呤组，n = 323）的生存率和排斥反应情况相似。在治疗患者中（MMF组，n = 289；硫唑嘌呤组，n = 289），与硫唑嘌呤组相比，MMF组1年时死亡率显著降低（18例[6.2%]死亡 vs 33例[11.4%]死亡；P = 0.031），排斥反应治疗需求也显著降低（65.7% vs 73.7%；P = 0.026）。MMF组中发生≥3A 级排斥反应的患者较少（45.0% vs 52.9%；P = 0.055），或需要使用鼠单克隆抗CD3抗体或抗胸腺细胞球蛋白治疗的患者较少（15.2% vs 21.1%；P = 0.061），存在这种趋势。机会性感染（主要是单纯疱疹）在MMF组更为常见（53.3% vs 43.6%；P = 0.025）。