小剂量来氟米特诱导治疗增殖型狼疮肾炎的多中心前瞻性研究

Efficacy of low- dose leflunomide in lupus nephritis： A multi- center prospective study

目的探讨小剂量来氟米特联合泼尼松诱导治疗增殖型狼疮肾炎（LN）的临床疗效和安全性。方法采用前瞻性、多中心、随机对照的研究方法，纳入15家临床肾脏病中心2013年11月至2015年11月经肾活检病理检查确诊为增殖型狼疮肾炎患者为研究对象。入选患者被随机分为来氟米特组和环磷酰胺组，在口服泼尼松的基础上，分别给予口服小剂量来氟米特（20mg／d，总疗程24周），或静脉环磷酰胺（总剂量0．8-1．0g，1次，4周×6次）诱导治疗。治疗期间监测24h尿蛋白量、肝肾功能、抗双链DNA滴度、血沉和补体等指标，记录药物不良反应。24周后比较两组患者的临床缓解率（完全缓解率＋部分缓解率），系统性红斑狼疮疾病活动度评分（SLEDAI）、24h尿蛋白量、血白蛋白、抗dsDNA抗体和补体c3的变化及药物安全性。结果共100例LN患者人组本临床试验，来氟米特组48例，环磷酰胺组52例。24周诱导治疗后，来氟米特组临床缓解率为79％（95％CI为67％-90％），环磷酰胺组为69％（95％CI为56％-82％），两组临床缓解率的差异无统计学意义（P=0．35）；来氟米特组和环磷酰胺组完全缓解率分别为23％（95％CI为11％-35％）和27％（95％C1为24％-30％），两组完全缓解率的差异亦无统计学意义（P=0．64）。与治疗前组相比，两组患者治疗后24h尿蛋白量、SLEDAI、抗dsDNA抗体滴度均有下降；血白蛋白、补体c3水平均有上升（均P〈0．05）。但来氟米特组与环磷酰胺组间比较差异无统计学意义。两组患者不良事件发生率的比较差异亦无统计学意义。结论来氟米特联合泼尼松诱导治疗增殖型狼疮肾炎的临床疗效与环磷酰胺相当，其对维持期LN的远期疗效尚有待进一步研究。

Objective To investigate the efficacy of leflunomide combined with prednisone inthe induction therapy of proliferative lupus nephritis （LN）. Methods A prospective, multicenter, randomized controlled clinical trial was conducted in patients with biopsy-proved proliferative lupus nephritis recruited from 15 renal centers from 2013 to 2015. Patients were randomized to two groups. Oral leflunomide or intravenous cyclophosphamide was given to patients in each group. Both groups received a tapering course of oral prednisone therapy. All patients were followed up for 24 weeks. The blood biochemistly, urine index, clinical curative effect and adverse reaction were recorded and analyzed statistically. Results A total of 100 patients were enrolled in this clinical trial, including 48 patients in leflunomide group and 52 patients in eyelophosphamide group. After 24 weeks, the overall response rate was 79% （95% CI 67%-90% ） in the leflunomide group and 69% （95% CI 56%-82%） in the cyclophosphamide group. 23% （95%CI 11%-35%） of patients in leflunomide group showed complete remission compared with 27% （95%CI 24%-30%） in cyclophosphamide group （P= 0.35）. The levels of 24- hr urine protein excretion, SLEDAI and anti- dsDNA antibody titers were decreased in patients treated with leflunomide group after 24-weeks treatment. And the levels of serum albumin and complement 3 after treatment were significantly higher compared with these before treatment. There was also no significant difference in changes of 24-hr urine protein excretion, SLEDAI score, anti-dsDNA antibody titers, serum albumin and complement C3 levels after treatment between two groups. Incidence of adverse events did not differ between the leflunomide and eyelophosphamide group. Conclusions Leflunomide combined with prednisone showed same efficacy compared with cyclophosphamide as induction therapy for lupus nephritis. Leflunomide might be an useful medicine in the induction therapy of lupus nephritis.