强化剂量与标准剂量的麦考酚钠肠溶片用于肾移植术后免疫抑制治疗中有效性与安全性的Meta分析

Efficacy and safety of an intensified dosing regimen versus a standard dosing regimen of enteric-coated mycophenolate sodium in immunosuppressive therapy after kidney transplantation: a meta-analysis

目的:评价肾移植术后采用麦考酚钠肠溶片(EC-MPS)强化剂量与标准剂量的疗效和安全性。方法:计算机检索Medline,Embase,Pubmed,The Cochrane Library和CBM、CNKI、VIP、Wan Fang Data,纳入肾移植术后采用EC-MPS强化剂量与标准剂量进行免疫抑制治疗的随机对照试验(RCT)、队列研究,检索时限为建库至2017年11月,并追溯纳入研究的参考文献。在评价纳入研究的方法学质量和提取有效数据后,采用Rev Man5.1进行Meta分析。结果:纳入3个研究,共300例肾移植术后患者。Meta分析结果显示:第6个月时强化剂量组经活检证实的急性排斥反应(BPAR)发生率低于标准剂量组且2组差异有显著性[RR=0.20,95%CI(0.07,0.62),P=0.005];第6个月时2组的的移植物丢失/死亡率[RR=0.78,95%CI(0.25,2.43),P=0.67]差异均无显著性;强化剂量组的胃肠道不良反应发生率高于标准剂量组,但2组差异无显著性[1.15(0.98,1.35),P=0.09];第6个月时强化剂量组的感染发生率(53.62%)低于标准剂量组(56.79%),且2组差异有显著性[RR=0.81,95%CI(0.68,0.97),P=0.02];其他纳入分析的安全性指标差异均无显著性。结论:基于当前临床证据,肾移植术后早期予以强化剂量的EC-MPS是安全的且有较低的BPAR发生率,可见,肾移植术后早期予以足量的霉酚酸(MPA)暴露量可有效预防排斥反应的发生,而远期结果由于缺乏高质量且大样本的随机对照研究,仍有待进一步探讨。

OBJECTIVE To evaluate the efficacy and safety of an intensified dosing（ ID） regimen versus a standard dosing（ SD） regimen of enteric-coated mycophenolate sodium（ EC-MPS） in patients receiving immunosuppressive therapy after kidney transplantation. METHODS Medline,Embase,Pubmed,The Cochrane Library,and CBM,CNKI,VIP,Wan Fang Data were searched from their establishment dates to November 2017 to include randomized controlled trials（ RCTs） and cohort studies of an intensified dosing regimen versus a standard dosing regimen of EC-MPS in patients after kidney transplantation. After methodology quality was evaluated and efficacy data were extracted,the software Rev Man 5. 1 was adopted to perform meta-analysis. RESULTS A total of 3 studies（ n = 300） were included finally. The results of meta-analysis showed that the incidence of biopsy proven acute rejection（ BPAR） was significantly lower in the ID group over a 6-month study period [RR = 0. 20,95 % CI（ 0.07,0. 62）,P = 0. 005]. There was no statistical significance in difference of the incidence of graft loss or death between the two groups over a 6-month study period [RR = 0. 78,95 % CI（ 0. 25,2. 43）,P = 0. 67]. The incidence of gastrointestinal adverse events of the ID group was higher over a 6-month study period while there was no statistical significance between the two groups [1. 15（ 0. 98,1. 35）,P = 0. 09]. Furthermore,the incidence of infections was lower in the ID group compared with the SD group,but with no statistical significance [RR = 0. 81,95 % CI（ 0. 68,0. 97）,P = 0. 02]. CONCLUSION Based on current evidences,the ID group has lower incidence of BPAR and comparable safety compared with the SD group. Thus it can be seen that adequate early mycophenolic acid（ MPA） exposure is an important determinant for effective rejection prophylaxis,but the long-term results need to be further studied.