他克莫司治疗狼疮性肾炎的系统评价

发布时间：2018-08-13 11:16

【摘要】：目的：系统评价糖皮质激素联合他克莫司治疗成人狼疮性肾炎的疗效和安全性。方法：利用计算机检索Cochrane图书馆对照试验的中心资料库、Pubmed数据库、OVID数据库、万方数据库、中文期刊全文数据库自建库至2013年12月关于他克莫司治疗狼疮性肾炎的前瞻性临床研究（CCT）或随机对照研究（RCT），并同时手工检索论文中的参考文献。英文检索关键字："Tacrolimus/FK506,Lupus nephritis/LN/Lupusglomerulosclerosis,Randomized clinical trials"。中文检索关键字：“普乐可复/他克莫司/FK506，系统性红斑狼疮/狼疮性肾炎”。根据Jadad评分方法评价纳入研究文献的质量。用RevMan5.1软件对提取资料进行Meta分析。结果：共纳入10篇随机对照研究和1篇队列研究，共504例病人，其中他克莫司组251人，，对照组中糖皮质激素联合环磷酰胺为218例，糖皮质激素联合安慰剂对照为35例。对纳入文献的安全性及有效性指标分别应用RevMan5.1软件绘制倒漏斗图，结果显示倒漏斗图散点分布大致左右对称，提示可能存在较小的发表偏倚。分析提取数据显示,TAC组获得部分缓解的平均时间较环磷酰胺更短，差异有统计学意义[MD=-1.05,95%CI(-1.61,-0.49),P=0.0002]。1、疗效方面：(1)诱导治疗6个月后根据是否为IV型狼疮性肾炎进行亚组分析，TAC组IV型LN的完全缓解率[OR=2.23，95%CI（1.08,4.63），P=0.03]显著高于CTX组，但有效率（P=0.05）、尿蛋白下降水平（P=0.20）、血清白蛋白改善程度（P=0.72）及系统性红斑狼疮活动指数（P=0.09）与对照组相比无显著性差异。对其他病理类型亚组进行分析显示完全缓解率、有效率、尿蛋白下降水平、血清白蛋白改善情况和系统性红斑狼疮活动性指数均显著优于对照组（P0.001）。（2）治疗达3个月时TAC组的疗效显著优于对照组（P0.05）。2、安全性方面：（1）TAC组肝损伤（P=0.03）、白细胞下降（P=0.0005）、月经紊乱发生率（P=0.0002）显著低于对照组。感染、胃肠道不适、肾毒性、血压升高发生率与对照组相比无统计学差异（P0.05）。(2)TAC糖耐量异常的发生率显著高于对照组（包含安慰剂组和环磷酰胺组）（P=0.01）,亚组分析显示TAC组糖耐量异常发生率较CTX组相似（P=0.05）。结论：1.他克莫司可迅速、有效地改善系统性红斑狼疮的全身症状，降低各种病理类型狼疮性肾炎患者的尿蛋白、升高血清白蛋白，诱导治疗3个月时有效率可达81.48%。2.他克莫司可有效提高各种病理类型的临床缓解率，特别是非IV型或复合型狼疮性肾炎患者的临床缓解率。3.他克莫司的糖耐量异常发生率高于对照组，肝毒性、肾毒性、生殖毒性、血压升高、胃肠道不良反应、感染、白细胞下降的副作用与对照组相似或低于对照组，提示临床应用安全性良好。
[Abstract]:Objective: to evaluate the efficacy and safety of glucocorticoid combined with tacrolimus in the treatment of adult lupus nephritis. Methods: the central database of Cochrane library was searched by computer. A prospective clinical study of tacrolimus in the treatment of lupus nephritis (CCT) or a randomized controlled study (RCT),) was established from the full text database of Chinese journals until December 2013. Tacrolimus / FK506 Lupus nephritis / LN / Lupus conglomerulosclerosissis / Randomized clinical trials. Keywords: Procor / tacrolimus / FK506, systemic lupus erythematosus / lupus nephritis. The quality of the literature included in the study was evaluated according to the Jadad scoring method. The extracted data were analyzed by Meta with RevMan5.1 software. Results: a total of 504 patients were enrolled in 10 randomized controlled trials and 1 cohort study. Among them, 251 were tacrolimus group, 218 were glucocorticoid combined with cyclophosphamide and 35 were glucocorticoid plus placebo control group. The RevMan5.1 software was used to draw the inverted funnel graph for the safety and effectiveness indexes of the literature. The results showed that the distribution of the scattered points of the inverted funnel graph was approximately symmetrical to the left and right, suggesting that there might be a small publication bias. The average time of partial remission in TAC group was shorter than that in cyclophosphamide group. The difference was statistically significant [MD-1.0595 CI (-1.61U -0.49) Pu 0.0002] .1.Therapeutic effect: (1) after 6 months of induction therapy, the complete remission rate of type IV LN in TAC group [OR2.2395CI (1.084.63)] was significantly higher than that in CTX group, (1) after 6 months of induction therapy, the complete remission rate of type IV LN in TAC group was significantly higher than that in CTX group. But there were no significant differences in effective rate (P0. 05), urinary protein level (P0. 20), serum albumin improvement (P0. 72) and systemic lupus erythematosus activity index (P0. 09) compared with the control group. The analysis of other pathological subgroups showed complete remission rate, effective rate, and decreased level of urinary protein. The improvement of serum albumin and the activity index of systemic lupus erythematosus were significantly better than those of the control group (P0. 001). (2) for 3 months. The safety of TAC group was significantly better than that of the control group (P0.05). The safety aspects were as follows: (1) liver injury (P0. 03) and leukopenia (P0. 0005) in TAC group. The incidence of menstrual disorder (P0. 0002) was significantly lower than that in the control group. Infection, gastrointestinal discomfort, nephrotoxicity, There was no significant difference in the incidence of elevated blood pressure between the two groups (P0.05). (2). The incidence of abnormal glucose tolerance in TAC group was significantly higher than that in control group (P0. 01). The incidence of abnormal glucose tolerance in TAC group was similar to that in CTX group (P0. 01). Conclusion 1. Tacrolimus can rapidly and effectively improve systemic lupus erythematosus symptoms, reduce urine protein of patients with various pathological types of lupus nephritis, increase serum albumin, and the effective rate of induction therapy for 3 months can reach 81.48.2. Tacrolimus can effectively improve the clinical remission rate of various pathological types, especially in patients with non-IV or complex lupus nephritis. The incidence of impaired glucose tolerance in tacrolimus was higher than that in the control group, and the side effects of hepatotoxicity, nephrotoxicity, reproductive toxicity, elevated blood pressure, gastrointestinal adverse reactions, infection and leukopenia were similar or lower than those in the control group. It suggests that the clinical application is safe.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R593.242

【参考文献】