吗替麦考酚酯联合来氟米特多靶点诱导治疗狼疮肾炎的临床疗效

目的评估吗替麦考酚酯（MMF）联合来氟米特（LEF）多靶点诱导治疗狼疮肾炎疗效及安全性。方法选取2010年5月至2013年6月惠州市中心人民医院经肾活检确诊为Ⅲ型、Ⅳ型、Ⅲ＋Ⅴ型、Ⅳ＋Ⅴ型狼疮肾炎且慢性指数（CI）〈4分、年龄大于18岁患者70例，随机分为多靶点治疗组（MMF1．0g／d，LEF10mg／d，共6个月）及环磷酰胺冲击治疗对照组[IV．CYC（0．5～1．0）g／m^2，每月1次，共6个月]，每组35例。两组均接受起始剂量甲基泼尼松龙500mg冲击治疗3d，后泼尼松0．5mg·kg^-1·d^-1口服维持4周并逐渐减量，评价肾脏完全缓解（CR）及部分缓解（PR）以及系统性红斑狼疮疾病活动评分（SLEDAI）、抗双链DNA抗体（ds-DNA）值的变化。分析比较两组胃肠道反应、上呼吸道感染、中性粒细胞减少、月经紊乱、带状疱疹等主要不良反应的发生情况。结果共有62例患者纳入统计，其中多靶点治疗组33例，对照组29例，多靶点治疗组CR及CR或PR率与对照组比较，差异无统计学意义。多靶点治疗组Ⅳ＋Ⅴ型CR率高于对照组（44．4％比12．5％，P=0．026），多靶点治疗组Ⅲ＋Ⅴ型CR率高于对照组（60％比20锈，P〈0．05），两组Ⅳ＋Ⅴ型PR或CR率比较差异亦有统计学意义（77．8％比50％，P=0．018）。多靶点治疗组SLEDAI评分、ds-DNA变化与对照组比较差异无统计学意义。多靶点治疗组与对照组比较，胃肠道反应及上呼吸道感染发生率低于对照组（6．1％比48．3％，P=0．032；9．1％比24．1％，P=0.041）。两组均出现2例中性粒细胞减少，对照组还出现月经紊乱2例（6．9％），带状疱疹2例（6．9％）。结论多靶点诱导狼疮肾炎疗效及安全性均优于传统治疗方案。

Clinical efficacy of multi-target induction therapy with mycophenolate mofetil and leflunomide on lupus nephritis

Objective To assess the efficacy and safety of mycophenolate mofetil （MMF） combined with Leflunomide （LEF） in the multi-target induction therapy for lupus nephritis. Methods Between May 2010 and June 2013, a total of 70 cases of kidney biopsy proved lupus nephritis at Huizhou Central People＇s Hospital were recruited in this study. Of these patients, the classification of lupus nephritis included type Ⅲ, Ⅳ, Ⅲ＋Ⅴ, and Ⅳ＋Ⅴ, the score of chronic index （CI） was below 4, and the patient age was below 18 years old. The patients were randomly assigned to either multi-target induction therapy group [MMF （1.0 g/d） and LEF （10 mg/d） for 6 months] or intravenous cyelophosphamide pulse therapy group （as the control group） [IV-CYC （0.5-1.0）g/m^2, one times a month, 6 months] , with 35 patients in each group, The two groups received methylprednisolone （MP） pulse therapy at an initial dose of 500 mg for 3 d, followed by 4-week maintenance with oral prednisone （0.5 mg·kg^-1·d^-1 ） before tapering. The renal complete remission （CR） or partial remission （PR）, reduction in SLEDAI scores, and anti-ds-DNA antibodies were evaluated. Incidence of major adverse reactions, such as gastrointestinal symptoms, upper airway infection, neutropenia,menstrual disorders and shingles, was noted and compared between the two groups. Results 62 patients were included in the final analysis, including 33 from the multi-target induction therapy group, and 29 from the control group. The overall rate of CR or PR did not differ significantly between the two group （P〉0.05）. However, the multi-target induction therapy group showed higher rates of CR in patients with class Ⅳ＋ Ⅴ （44.4% vs 12.5%, P=0.026）, and class Ⅲ＋Ⅴ （60% vs 20%, P〈0.05） lupus nephritis, compared with the control group. Moreover, the CR or PR rate of class Ⅳ＋ Ⅴ lupus nephritis in multi-target therapy group was notably much higher than that in control group （77.8% vs 50%, P=0.018）. The SLEDAI