他克莫司原研药与仿制药在肾移植术后早期患者中的浓度、有效性与安全性对比评价

Evaluation of concentration, effectiveness and safety of original and generic tacrolimus in patients at early stage after kidney transplantation

目的:评价他克莫司原研药和仿制药的浓度、有效性和安全性在中国肾移植术后早期患者中的一致性。方法:通过筛选纳入2015年1月到2021年1月肾移植术后使用他克莫司原研药(普乐可复)、仿制药(赛福开)的病例。采用倾向性得分匹配2组体质量及CYP3A5基因分型后,比较术后3,7,14d的剂量校正谷浓度(dose-adjusted trough concentration,C0/D)、有效性和安全性的差异。结果:最终初步纳入137例患者(411个C0点),其中普乐可复58例(174个C0点),赛福开79例(237个C0点)。倾向性得分匹配后共纳入96例患者(288个C0点),每组各48例。2组患者在第3天,第7天,第14天的C0/D和C0达标率的差异无统计学意义(P>0.05)。有效性方面,2组患者6个月的存活率均为100%,普乐可复组急性排斥反应发生率为3.3%,赛福开组为1.7%,2组间差异无统计学意义(P>0.05)。安全性方面,普乐可复组和赛福开组在肾移植术后6个月内的肝功能异常均为1例、院内感染分别为3例和1例、院外感染分别为3例和6例、总感染事件分别为6例和7例,血糖异常分别为31例和33例,2组间差异均无统计学意义(P>0.05)。结论:他克莫司原研药普乐可复和仿制药赛福开在肾移植术后早期患者中的C0/D、C0达标率、有效性和安全性具有一致性。

OBJECTIVE To evaluate the consistency of concentration,effectiveness,and safety of the original and generic tacrolimus in patients at early stage after kidney transplantation.METHODS From January 2015 to January 2021,patients receiving original tacrolimus prograf and generic tacrolimus saifukai after kidney transplantation were selected.The differences in dose-adjusted trough concentration(C0/D),effectiveness and safety were compared on day 3,7 and 14 between the two groups after propensity score matching(PSM).RESULTS A total of 137 patients(411 C0 points)were initially enrolled,including 58 patients(174 C0 points)receiving prograf and 79 patients(237 C0 points)with saifukai.A total of 96 patients(288 C0 points)were matched after PSM,with 48 patients in each group.There were no significant differences in C0/D and C0 achievement rate between the two groups on day 3,7 and 14(P>0.05).For effectiveness,the 6-month survival rate in both groups was 100%,and the incidence of acute rejection was 3.3%in the prograf group and 1.7%in the saifukai group,with no statistically significant difference(P>0.05).For safety,there were both 1 case of abnormal liver function,3 cases and 1 case of hospital infection,3 cases and 6 cases of out-of-hospital infection,6 cases and 7 cases of total infection events,and 31 cases and 33 cases of abnormal blood glucose within 6 months after kidney transplantation in the prograf and saifukai group,respectively,with no statistically significant difference(P>0.05).CONCLUSION The C0/D,C0 achievement rate,effectiveness and safety of prograf and saifukai are consistent in patients with early renal transplantation.