目的 前瞻性观察激素联合霉酚酸酯(MMF)和环磷酰胺(CYC)(多靶点组)诱导治疗狼疮性肾炎(LN)的疗效及安全性,并与传统的激素联合环磷酰胺静脉冲击疗法(IVCY组)进行比较.方法 50例经肾活检确诊为Ⅲ型、Ⅳ型、Ⅴ型、Ⅲ+Ⅴ型和Ⅳ+Ⅴ型的LN患者随机分为多靶点组(n=25) 和传统的IVCY组(n=25),两组患者均使用口服泼尼松1 mg/kg开始并逐渐减量.在多靶点组中MMF的剂量为1 g/d,MMF血药浓度(MPA-AuC0-12h)目标值为20~30 mg·h/L;CYC剂量为每2周0.6 g静脉滴注,共6次.IVCY组中CYC剂量为每月1次静脉滴注1.0 g,共6次.诱导治疗疗程6个月.疗效观察的主要指标为完全缓解率,比较两组的疗效和不良反应.结果 多靶点组与IVCY组的基线特征与临床指标差异无统计学意义,多靶点组在诱导3个月时(44.0% vs 16.0%, P<0.05) 和6个月时(72.0% vs 44.0%, P<0.05) 的完全缓解率均显著高于IVCY组.对于Ⅳ+Ⅴ型LN,多靶点组的完全缓解率显著高于IVCY组(70.0% vs 25.0%, P<0.05).多靶点组达到完全缓解所用时间显著短于IVCY组[(17.55±9.53)周 vs (24.13±9.92)周,P<0.05].诱导6个月时多靶点组的24 h尿蛋白下降幅度显著大于IVCY组 [(86.8±20.9)% vs (66.7±30.5)%,P<0.01].多靶点组与IVCY组总不良反应相当(28.0% vs 52.0%, P>0.05),其中多靶点组的主要不良反应为胃肠道不适(8%) 和感染(12%),IVCY组的主要不良反应为胃肠道不适(16%)、感染(16%)、脱发(8%)和月经紊乱(8%),两组患者无一例死亡.结论 激素联合MMF与CYC组成的多靶点疗法治疗LN疗效优于传统CYC单药疗法,尤其对Ⅴ+Ⅳ型LN疗效显著且不良反应发生率低,且多靶点组在早期诱导缓解LN疗效显著.多靶点疗法的临床疗效和对远期预后的影响还需要大样本多中心和长期随访的临床研究.%Objective To prospectively investigate the efficacy and safety of corticosteroid along with mycophenolate mofetil (MMF) and cyclophosphamide(CYC) (multi-target group) compared with traditional corticosteroid plus cyclophosphamide (CYC alone) in the induction treatment of lupus nephritis (LN).Methods Fifty SLE patients with biopsy proven class Ⅲ, Ⅳ, Ⅴ, Ⅲ+Ⅴ and Ⅳ+Ⅴ were randomly recruited into multi-target group (n=25) and IVCY group (n=25).Both groups were initially treated with oral prednisone (1 mg/kg) then tapered.In multi-target group, the dose of MMF was 1 g/d and its blood level (MPA-AuC0-12h) was in the range of 20-30 mg·h/L, and CYC was intravenously given in 0.6 g every 2 weeks for 6 times.In IVCY group, the dose was 1.0 g intravenously monthly for 6 times.The length of induction was 6 months.The primary efficacy endpoint was complete remission rate (CR, defined as Urinary protein<0.4 g/24 h, serum albumin≥35 g/L, normal serum creatinine and no extra-renal flare).The efficacy and safety between the two groups were compared.Results There is no significant differences in baseline characteristics, clinical parameters or pathologic profile between the two groups.The CR rate in multi-target group, compared with that in ⅣCY group, was significantly higher at 3 months and 6 months (44.0% vs.16.0% P<0.05, 72.0% vs.44.0% P<0.05, respectively).For the LN class Ⅳ+Ⅴ, the CR rate in multi-target group was significantly higher than that in IVCY group, while the among other classes it was not calculated owing to small size of samples.The time length to CR in the multi-target group was significantly shorter than that in IVCY group [(17.55±9.53) weeks vs.(24.13±9.92) weeks, P<0.05).The urine protein fell more dramatically in multi-target group [(86.8±20.9)% vs.(66.7±30.5)%, P<0.01].The overall incidence of adverse events in both groups was similar (28.0% vs.52.0%, P<0.05), the major adverse events were gastrointestinal discomfort (8%) and infection (12%) in the multi-target group, while gastrointestinal discomfort (16%), infection (16%), alopecia (8%) and menstrual disorders (8%) in IVCY group.No death was reported.Conclusion Multi-target therapy composed of corticosteroid plus mycophenolate and cyclophosphamide, when compared with traditional IVCY, is more effective and safe in inducing remission in lupus nephritis, particularly for class Ⅴ+Ⅳ.Moreover, Multi-target therapy provides a significantly higher CR rate in the early induction period.However, multi-center trials with long period of follow-up are needed to confirm the clinical efficacy and long-term prognosis of multi-target therapy.
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