Lancet. 1994 Aug 13;344(8920):423-8.
Studies in the USA and Japan have shown that tacrolimus (FK506) is a potent immunosuppressant. To compare the efficacy and safety of tacrolimus-based and conventional cyclosporin-based immunosuppressive regimens we recruited 545 liver transplant recipients from eight European centres into a randomised open trial. Analysis of the data at 12 months post-transplant showed that tacrolimus was associated with a significant reduction in acute, refractory acute, and chronic rejection episodes. The rates were, for acute rejection, tacrolimus 40.5% vs 49.8% cyclosporin (p = 0.040; absolute difference 9.3% [95% CI 0.9-17.8%]). For refractory acute and chronic rejections the comparisons were 0.8% vs 5.3% (p = 0.005) and 1.5% vs 5.3% (p = 0.032). There results were seen despite significantly lower corticosteroid usage. The incidence of infection was also lower in patients receiving tacrolimus. Patient and graft survival rates were not significantly different (tacrolimus 82.9% and 77.5%; cyclosporin 77.5% and 72.6%). Safety data were comparable--the most serious events being renal impairment, disturbances of glucose metabolism, and neurological complications--but these events were more common in the tacrolimus group. In this trial tacrolimus had advantages over cyclosporin in respect of lower rejection rates, even though less concurrent immunosuppression was administered.
美国和日本的研究表明，他克莫司（FK506）是一种强效免疫抑制剂。为比较以他克莫司为基础的免疫抑制方案和传统的以环孢素为基础的免疫抑制方案的疗效和安全性，我们从八个欧洲中心招募了545名肝移植受者，进行一项随机开放试验。移植后12个月的数据分析表明，他克莫司与急性、难治性急性和慢性排斥反应的显著减少相关。急性排斥反应的发生率，他克莫司组为40.5%，环孢素组为49.8%（p = 0.040；绝对差异9.3% [95% CI 0.9 - 17.8%]）。难治性急性和慢性排斥反应的比较结果分别为0.8% 对5.3%（p = 0.005）和1.5% 对5.3%（p = 0.032）。尽管皮质类固醇的使用量显著较低，但仍出现了这些结果。接受他克莫司治疗的患者感染发生率也较低。患者和移植物的存活率没有显著差异（他克莫司组分别为82.9%和77.5%；环孢素组分别为77.5%和72.6%）。安全性数据具有可比性——最严重的事件是肾功能损害、糖代谢紊乱和神经并发症——但这些事件在他克莫司组中更为常见。在这项试验中，他克莫司在降低排斥反应发生率方面优于环孢素，尽管同时给予的免疫抑制较少。
