肾移植术后应用骁悉与硫唑嘌呤的安全性评价

目的 系统评价肾移植术后免疫抑制剂骁悉(mycophenolate mofetil,MMF)与硫唑嘌呤(azathioprine,AZA)导致的不良反应发生情况.方法 计算机检索MEDLINE(1966～2004.6)、EMBASE(1984～2004.6)、Cochrane图书馆(2004第2期)及中国生物医学文献数据库(1979～2004.6),纳入涉及肾移植术后使用MMF与AZA出现不良反应的随机对照试验(RCT),对其方法 学质量进行评价后,采用RevMan 4.11软件进行统计分析.结果 共纳入24个RCT,涉及不同剂量MMF与AZA治疗肾移植术后的排斥反应.MMF的胃肠道不良反应发生率明显高于AZA,特别是MMF3 g/d组的呕吐、腹痛、腹泻发生率与AZA组比较有明显差异(P<0.05).MMF3 g/d组的巨细胞病毒感染发生率在6个月、1年及3年观察期内明显高于AZA组,其差异有统计学意义;MMF2 g/d组在1年随访期内感染发生率也高于AZA组.MMF3 g/d组的白细胞减少发生率明显高于AZA组,其差异有统计学意义;而MMF2 g/d组的白细胞减少发生率与AZA组相比差异不具统计学意义.MMF的血小板减少发生率低于AZA组,MMF3 g/d组与AZA组相比差异有统计学意义.MMF各组及AZA组皮肤肿瘤的发生率无明显差异.结论 MMF与AZA相比,其不良反应发生主要表现为较高的胃肠道不良反应、白细胞减少发生率和机会感染发生率,较低的血小板减少发生率.而且不良反应的发生呈现一定的剂量效应关系.

Safety of Mycophenolate Mofetil versus Azathioprin in Renal Transplantation: A Systematic Review

Objective To evaluate the safety of mycophenolate mofetil (MMF) versus azathioprine (AZA) for rejection after renal transplantation.Methods We searched MEDLINE (1966Jun. 2004), EMBASE (1984Jun. 2004), The Cochrane Library (Issue 2, 2004) and Chinese Biomedical Database (CBM, 1979Jun. 2004). Randomized controlled trials (RCTs) comparing MMF with AZA for rejection after renal transplantation were included. The quality of included studies such as randomization, blinding, allocation concealment was evaluated and meta-analysis was performed using RevMan 4.1.1 software.Results Twenty-Four RCTs comparing MMF (2 g/day or 3 g/day) with AZA for rejection after renal transplantation were identified. The digest system morbidity of MMF group was higher than that of AZA group. The incidence of vomiting, bellyache and diarrhea of MMF 3 g/day group was statistical by higher than that of AZA group (P<0.05). The cytom egalovirus (CMV) infection morbidity of MMF 3 g/day group during 6 months, 1 year and 2 years follow-up was higher than AZA group with statistical difference, but for MMF 2 g/day group, this difference was only seen during 1 year follow-up. Leukopenia incidence of MMF 3g/day group was higher than AZA group with statistical difference, but this difference was not seen in MMF 2 g/day group. Thrombocytopenia incidence of MMF 3 g/day group was lower than AZA group with statistical difference. For skin carcinoma morbidity, no statistical difference was found among MMF 3 g/day, MMF 2 g/day and AZA groups.Conclusions Compared with AZA, MMF represents higher digest system side-effects incidence, higher morbidity of leucopenia and CMV infection and lower incidence of thrombocytopenia. The dose-response relationship of adverse drug reaction is found.