多靶点疗法治疗狼疮性肾炎的安全性与有效性评价
|
摘要
目的评价激素联合他克莫司(TAC)、霉酚酸酯(MMF)和环磷酰胺(IVC)多靶点治疗狼疮性肾炎(LN)的有效性和安全性。方法系统检索PubMed、Embase、Cochrane Library、CBM、CNKI、万方、维普数据库。收集多靶点诱导治疗LN的随机对照试验(RCT),应用Review Manager 5.3软件对数据进行Meta分析。结果共10篇国内进行的RCT共计1151例患者被纳入到本次Meta分析中,结果显示多靶点组的完全缓解率高于IVC组(RR:1.83,95%CI:1.59～2.11,P <0.000 01),但对Ⅲ型、Ⅴ+Ⅲ型的LN患者,多靶点治疗无明显优势;与IVC组相比,多靶点组抗dsDNA转阴率高,SLEDAI评分变化、血清白蛋白升高和尿蛋白减少更明显,且胃肠道反应、白细胞减少、肝功能异常、脱发和月经失调的发生率明显低于IVC组,但新发高血压的发生率高于IVC组,感染和高血糖的发生率比较,差异均无统计学意义。结论对我国Ⅳ型、Ⅴ型和Ⅴ+Ⅳ型的LN患者,多靶点治疗疗效优于IVC组,且安全性更高。
Objective To evaluate the efficacy and safety of multitarget therapy for lupus nephritis(LN) by hormone combined with tacrolimus(TAC), mycophenolate mofetil(MMF) and intravenous cyclophosphamide(IVC). Methods The randomised control trials(RCTs) of multitarget therapy for LN were retrieved from PubMed,Embase, Cochrane Library, CBM, CNKI, Wanfang, and VIP Database. According to inclusion and exclusion criteria, the literatures were screened and meta-analysis was conducted by Review Manager 5.3 software. Results Ten RCTs were included finally, totaling 1151 patients. The meta-analysis showed that the multitarget therapy had higher complete response rate than that of the IVC group(RR: 1.83, 95% CI: 1.59 to 2.11: P < 0.000 01), but for patients with type Ⅲ and Ⅴ+Ⅲ LN, there was no obvious advantage. Compared with the IVC group, multitarget therapy showed higher anti-dsDNA conversion rate, more obvious SLEDAI score changes, serum albumin rising and urinary protein reduction, but also the incidence of gastrointestinal reactions, leukopenia, liver dysfunction,alopecia, menstrual disorders were significantly lower. However, the rate of new onset of hypertension was higher than that of the IVC group. There was no significant difference in the rate of infection and hyperglycemia.Conclusion For patients with type Ⅳ, Ⅴ and Ⅴ+Ⅳ LN in China, the multitarget therapy is superior to IVC alone, and safer.
Objective To evaluate the efficacy and safety of multitarget therapy for lupus nephritis(LN) by hormone combined with tacrolimus(TAC), mycophenolate mofetil(MMF) and intravenous cyclophosphamide(IVC). Methods The randomised control trials(RCTs) of multitarget therapy for LN were retrieved from PubMed,Embase, Cochrane Library, CBM, CNKI, Wanfang, and VIP Database. According to inclusion and exclusion criteria, the literatures were screened and meta-analysis was conducted by Review Manager 5.3 software. Results Ten RCTs were included finally, totaling 1151 patients. The meta-analysis showed that the multitarget therapy had higher complete response rate than that of the IVC group(RR: 1.83, 95% CI: 1.59 to 2.11: P < 0.000 01), but for patients with type Ⅲ and Ⅴ+Ⅲ LN, there was no obvious advantage. Compared with the IVC group, multitarget therapy showed higher anti-dsDNA conversion rate, more obvious SLEDAI score changes, serum albumin rising and urinary protein reduction, but also the incidence of gastrointestinal reactions, leukopenia, liver dysfunction,alopecia, menstrual disorders were significantly lower. However, the rate of new onset of hypertension was higher than that of the IVC group. There was no significant difference in the rate of infection and hyperglycemia.Conclusion For patients with type Ⅳ, Ⅴ and Ⅴ+Ⅳ LN in China, the multitarget therapy is superior to IVC alone, and safer.
引文
[1]Almaani S,Meara A,Rovin BH.Update on lupus nephritis[J].Clin J Am Soc Nephrol,2017,12(5):825-835.
[2]Jaryal A,Vikrant S.Current status of lupus nephritis[J].Indian J Med Res,2017,145(2):167-178.
[3]Yap DY,Tang CS,Ma MK,et al.Survival analysis and causes of mortality in patients with lupus nephritis[J].Nephrol Dial Transplant,2012,27(8):3248-3254.
[4]Hanaoka H,Kiyokawa T,Iida H,et al.Comparison of renal resp onse to four different induction therapies in Japanese pa tients with lupus nephritis classⅢorⅣ:Asingle-centre retrospective study[J].PLoS One,2017,12(4):e175152.
[5]Steinberg AD,Decker JL.A double-blind controlled trial comparing cyclophosphamide,azathiop rine and placebo in the treatment of lupus glomerulonephritis[J].Arthritis Rheum,1974,17(6):923-937.
[6]黎磊石,刘志红.肾小球疾病免疫抑制剂治疗的新方向--多靶点免疫抑制治疗[J].肾脏病与透析肾移植杂志,2007,16(1):3-4.
[7]鲍浩,章海涛,张馨,等.难治性狼疮性肾炎多靶点治疗前瞻性临床研究[J].肾脏病与透析肾移植杂志,2007,16(1):5-13.
[8]谢志娟,邓进.多靶点与静脉环磷酰胺冲击诱导治疗狼疮性肾炎的Meta分析[J].重庆医学,2013,42(31):3750-3753.
[9]Bao H,Liu ZH,Xie HL,et al.Succes sful treatment of classⅤ+Ⅳlupus nephritis with mul titarget therapy[J].JAm Soc Nephrol,2008,19(10):2001-2010.
[10]Liu Z,Zhang H,Liu Z,et al.Multitarget therapy for induction treatment of lupus nephritis:a randomized trial[J].Ann Intern Med,2015,162(1):18-26.
[11]张勇,林淑芃,陈德政,等.多靶点治疗Ⅳ型狼疮肾炎的临床疗效及对血清白细胞介素水平的影响[J].临床肾脏病杂志,2016,16(1):8-11.
[12]赵文喜,徐虹.联合用药多靶点治疗狼疮性肾炎临床效果及安全性分析[J].河北医科大学学报,2016,37(1):6 1-63.
[13]鲍浩,刘志红,胡伟新,等.多靶点诱导治疗增殖性和膜性狼疮性肾炎前瞻对照性临床研究[J].肾脏病与透析肾移植杂志,2009,18(3):201-206.
[14]许圣淳,陈樱花,刘正钊,等.多靶点治疗Ⅳ+Ⅴ型狼疮性肾炎的长期随访[J].肾脏病与透析肾移植杂志,2012,21(2):101-108.
[15]胡伟新,陈樱花,刘正钊,等.激素联合赛可平和他克莫司治疗狼疮性肾炎的前瞻性临床研究[J].肾脏病与透析肾移植杂志,2011,20(4):301-306.
[16]Zhang H,Liu Z,Zhou M,et al.Multitarget therapy for maintenance treatment of lupus nephritis[J].J Am Soc Nephrol,2017,28(12):3671-3678.
[17]蒋健,郭群,段荣.霉酚酸酯联合他克莫司治疗对狼疮性肾炎患者免疫学指标及活动指数的影响[J].临床和实验医学杂志,2017,16(4):367-370.
[18]黄金平,喻彦之,高武,等.多靶点诱导治疗增殖性和膜性狼疮肾炎的有效性和安全性临床研究[J].临床肾脏病杂志,2017,17(2):100-104.
[19]Ch an TM.Treatment of severe lupus nephritis:the new horizon[J].Nat Rev Nephrol,2015,11(1):46-61.
[20]Sundel R,Solomons N,Lisk L.Efficacy of mycophenolate mofetil in adolescent patients with lupus nephritis:evidence from a two-phase,prospective randomized trial[J].Lupus,2012,21(13):1433-1443.
[21]Palmer SC,Tunnicliffe DJ,Singh-Grewal D,et al.Induction and maintenance immunosuppression treatment of proliferative lupus nephritis:A network meta-analysis of randomized trials[J].Am J Kidney Dis,2017,70(3):324-336.
[22]张艳芳.他克莫司诱导治疗活动性狼疮性肾炎的meta分析[D].重庆:重庆医科大学,2016.
[23]张佩佩.他克莫司治疗狼疮性肾炎的Meta分析[D].乌鲁木齐:新疆医科大学,2016.
[24]苑克晶.他克莫司治疗狼疮性肾炎的系统评价[D].长春:吉林大学,2014.
[25]Zhang X,Ji L,Yang L,et al.The effect of calcineurin inhibitors in the induction and maintenance treatment of lupus nephritis:a systematic review and meta-analysis[J].Int Urol Nephrol,2016,48(5):731-743.
[2]Jaryal A,Vikrant S.Current status of lupus nephritis[J].Indian J Med Res,2017,145(2):167-178.
[3]Yap DY,Tang CS,Ma MK,et al.Survival analysis and causes of mortality in patients with lupus nephritis[J].Nephrol Dial Transplant,2012,27(8):3248-3254.
[4]Hanaoka H,Kiyokawa T,Iida H,et al.Comparison of renal resp onse to four different induction therapies in Japanese pa tients with lupus nephritis classⅢorⅣ:Asingle-centre retrospective study[J].PLoS One,2017,12(4):e175152.
[5]Steinberg AD,Decker JL.A double-blind controlled trial comparing cyclophosphamide,azathiop rine and placebo in the treatment of lupus glomerulonephritis[J].Arthritis Rheum,1974,17(6):923-937.
[6]黎磊石,刘志红.肾小球疾病免疫抑制剂治疗的新方向--多靶点免疫抑制治疗[J].肾脏病与透析肾移植杂志,2007,16(1):3-4.
[7]鲍浩,章海涛,张馨,等.难治性狼疮性肾炎多靶点治疗前瞻性临床研究[J].肾脏病与透析肾移植杂志,2007,16(1):5-13.
[8]谢志娟,邓进.多靶点与静脉环磷酰胺冲击诱导治疗狼疮性肾炎的Meta分析[J].重庆医学,2013,42(31):3750-3753.
[9]Bao H,Liu ZH,Xie HL,et al.Succes sful treatment of classⅤ+Ⅳlupus nephritis with mul titarget therapy[J].JAm Soc Nephrol,2008,19(10):2001-2010.
[10]Liu Z,Zhang H,Liu Z,et al.Multitarget therapy for induction treatment of lupus nephritis:a randomized trial[J].Ann Intern Med,2015,162(1):18-26.
[11]张勇,林淑芃,陈德政,等.多靶点治疗Ⅳ型狼疮肾炎的临床疗效及对血清白细胞介素水平的影响[J].临床肾脏病杂志,2016,16(1):8-11.
[12]赵文喜,徐虹.联合用药多靶点治疗狼疮性肾炎临床效果及安全性分析[J].河北医科大学学报,2016,37(1):6 1-63.
[13]鲍浩,刘志红,胡伟新,等.多靶点诱导治疗增殖性和膜性狼疮性肾炎前瞻对照性临床研究[J].肾脏病与透析肾移植杂志,2009,18(3):201-206.
[14]许圣淳,陈樱花,刘正钊,等.多靶点治疗Ⅳ+Ⅴ型狼疮性肾炎的长期随访[J].肾脏病与透析肾移植杂志,2012,21(2):101-108.
[15]胡伟新,陈樱花,刘正钊,等.激素联合赛可平和他克莫司治疗狼疮性肾炎的前瞻性临床研究[J].肾脏病与透析肾移植杂志,2011,20(4):301-306.
[16]Zhang H,Liu Z,Zhou M,et al.Multitarget therapy for maintenance treatment of lupus nephritis[J].J Am Soc Nephrol,2017,28(12):3671-3678.
[17]蒋健,郭群,段荣.霉酚酸酯联合他克莫司治疗对狼疮性肾炎患者免疫学指标及活动指数的影响[J].临床和实验医学杂志,2017,16(4):367-370.
[18]黄金平,喻彦之,高武,等.多靶点诱导治疗增殖性和膜性狼疮肾炎的有效性和安全性临床研究[J].临床肾脏病杂志,2017,17(2):100-104.
[19]Ch an TM.Treatment of severe lupus nephritis:the new horizon[J].Nat Rev Nephrol,2015,11(1):46-61.
[20]Sundel R,Solomons N,Lisk L.Efficacy of mycophenolate mofetil in adolescent patients with lupus nephritis:evidence from a two-phase,prospective randomized trial[J].Lupus,2012,21(13):1433-1443.
[21]Palmer SC,Tunnicliffe DJ,Singh-Grewal D,et al.Induction and maintenance immunosuppression treatment of proliferative lupus nephritis:A network meta-analysis of randomized trials[J].Am J Kidney Dis,2017,70(3):324-336.
[22]张艳芳.他克莫司诱导治疗活动性狼疮性肾炎的meta分析[D].重庆:重庆医科大学,2016.
[23]张佩佩.他克莫司治疗狼疮性肾炎的Meta分析[D].乌鲁木齐:新疆医科大学,2016.
[24]苑克晶.他克莫司治疗狼疮性肾炎的系统评价[D].长春:吉林大学,2014.
[25]Zhang X,Ji L,Yang L,et al.The effect of calcineurin inhibitors in the induction and maintenance treatment of lupus nephritis:a systematic review and meta-analysis[J].Int Urol Nephrol,2016,48(5):731-743.