【摘要】：目的：系統(tǒng)評價糖皮質(zhì)激素聯(lián)合他克莫司治療成人狼瘡性腎炎的療效和安全性。 方法：利用計算機檢索Cochrane圖書館對照試驗的中心資料庫、Pubmed數(shù)據(jù)庫、OVID數(shù)據(jù)庫、萬方數(shù)據(jù)庫、中文期刊全文數(shù)據(jù)庫自建庫至2013年12月關(guān)于他克莫司治療狼瘡性腎炎的前瞻性臨床研究（CCT）或隨機對照研究（RCT），并同時手工檢索論文中的參考文獻(xiàn)。英文檢索關(guān)鍵字："Tacrolimus/FK506,Lupus nephritis/LN/Lupusglomerulosclerosis,Randomized clinical trials"。中文檢索關(guān)鍵字：“普樂可復(fù)/他克莫司/FK506，系統(tǒng)性紅斑狼瘡/狼瘡性腎炎”。根據(jù)Jadad評分方法評價納入研究文獻(xiàn)的質(zhì)量。用RevMan5.1軟件對提取資料進(jìn)行Meta分析。 結(jié)果：共納入10篇隨機對照研究和1篇隊列研究，共504例病人，其中他克莫司組251人，，對照組中糖皮質(zhì)激素聯(lián)合環(huán)磷酰胺為218例，糖皮質(zhì)激素聯(lián)合安慰劑對照為35例。對納入文獻(xiàn)的安全性及有效性指標(biāo)分別應(yīng)用RevMan5.1軟件繪制倒漏斗圖，結(jié)果顯示倒漏斗圖散點分布大致左右對稱，提示可能存在較小的發(fā)表偏倚。分析提取數(shù)據(jù)顯示,TAC組獲得部分緩解的平均時間較環(huán)磷酰胺更短，差異有統(tǒng)計學(xué)意義[MD=-1.05,95%CI(-1.61,-0.49),P=0.0002]。1、療效方面：(1)誘導(dǎo)治療6個月后根據(jù)是否為IV型狼瘡性腎炎進(jìn)行亞組分析，TAC組IV型LN的完全緩解率[OR=2.23，95%CI（1.08,4.63），P=0.03]顯著高于CTX組，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）及系統(tǒng)性紅斑狼瘡活動指數(shù)（P=0.09）與對照組相比無顯著性差異。對其他病理類型亞組進(jìn)行分析顯示完全緩解率、有效率、尿蛋白下降水平、血清白蛋白改善情況和系統(tǒng)性紅斑狼瘡活動性指數(shù)均顯著優(yōu)于對照組（P0.001）。（2）治療達(dá)3個月時TAC組的療效顯著優(yōu)于對照組（P0.05）。2、安全性方面：（1）TAC組肝損傷（P=0.03）、白細(xì)胞下降（P=0.0005）、月經(jīng)紊亂發(fā)生率（P=0.0002）顯著低于對照組。感染、胃腸道不適、腎毒性、血壓升高發(fā)生率與對照組相比無統(tǒng)計學(xué)差異（P0.05）。(2)TAC糖耐量異常的發(fā)生率顯著高于對照組（包含安慰劑組和環(huán)磷酰胺組）（P=0.01）,亞組分析顯示TAC組糖耐量異常發(fā)生率較CTX組相似（P=0.05）。 結(jié)論：1.他克莫司可迅速、有效地改善系統(tǒng)性紅斑狼瘡的全身癥狀，降低各種病理類型狼瘡性腎炎患者的尿蛋白、升高血清白蛋白，誘導(dǎo)治療3個月時有效率可達(dá)81.48%。2.他克莫司可有效提高各種病理類型的臨床緩解率，特別是非IV型或復(fù)合型狼瘡性腎炎患者的臨床緩解率。3.他克莫司的糖耐量異常發(fā)生率高于對照組，肝毒性、腎毒性、生殖毒性、血壓升高、胃腸道不良反應(yīng)、感染、白細(xì)胞下降的副作用與對照組相似或低于對照組，提示臨床應(yīng)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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R593.242

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