雷公藤多苷与硫唑嘌呤维持治疗狼疮性肾炎的长期疗效和安全性

Triptergium wilfordii and azathioprine in maintenance therapy for lupus nephritis-a randomized controlled trial of single center

目的:前瞻性随机对照观察雷公藤多苷(TW)和硫唑嘌呤(AZA)维持治疗狼疮性肾炎(LN)的复发率及安全性。方法:2007年1月至2008年6月经诱导治疗获得临床完全缓解(CR)或部分缓解(PR)的增殖性LN患者,随机分配至TW组和AZA组,维持治疗24个月后,继续随访观察。主要观察指标为两组患者的复发率,次要观察指标包括复发时间、治疗期间新增CR例数、到达肾脏终点事件(包括终末期肾病、肌酐倍增、估算的肾小球滤过率下降≥30%)的例数、治疗中尿蛋白定量和血清肌酐的变化及不良事件等。结果:(1)截止至2014年4月,84例患者中位随访时间57.5月,TW组有10例(25.0%)患者复发,中位时间17.5月;AZA组9例(20.5%)患者复发,中位时间38个月。两组复发率及复发时间均无统计学差异;(2)TW组和AZA组到达肾脏终点事件的患者分别为14例(35.0%)和11例(25.0%),无统计学差异。治疗期间两组血清肌酐及尿蛋白无显著变化;(3)不良事件:TW组(75.0%)不良事件发生率与AZA组(59.1%)无统计学差异,其中月经紊乱的发生率明显高于AZA组,而白细胞减少显著降低,两组总的感染率无统计学差异,但是TW组阴道炎的发生率明显高于AZA组。结论:TW维持治疗LN的复发率与AZA维持治疗相当,虽然TW组月经紊乱的发生率高于AZA组,但两组总的不良事件无统计学差异。因此,TW是一种有效的维持期治疗药物。

Objective： To investigate the long-term effect of triptergium wilfordii on maintenance therapy of proliferative lupus nephritis（ LN） patients, comparing with azathioprine. Methodology： Eighty six patients with proliferative LN who received complete remission or partial remission from January 2007 to June 2008 were enrolled into this clinical trial. Before taking experimental drugs,two patients withdrew consents. According to the regimen of treatment,they were randomized to either triptergium wilfordii（ TW） group or azathioprine（ AZA） group. The duration of maintenance therapy was 24 months. The primary end point was the rate of relapse（ renal flare and extrarenal flare）. The secondary assessments included time to relapse,rate of reaching renal endpoint patients（ renal endpoint was defined as end-stage renal disease,doubling of the serum creatinine level,or a change of- 30% or greater in estimated GFR）,changes of proteinuria and SCr during treatment,adverse effects. The long term effects between two regimens of maintenance therapy for LN were compared. Results： The median follow-up was 57. 5 months（ interquartile range 18. 8,69. 0 months）. The rate of relapses was similar between two groups,while the media time of the relapse was 17. 5 months（ interquartile： 5,56）in TW and 38 months（ interquartile： 3,75） in AZA group,respectively. There was no significantly difference of serum creatinine,proteinuria and the level of anti-ds DNA between two groups during the first two years. Although the adverse events was higher in TW group（ 75. 0%） than that in AZA group（ 59. 1%）,but there was no statistical difference. The incidence of amenorrhea in TW group was significantly higher than that in AZA group while leukopenia was higher in AZA group. Both groups had a similar incidence of infection. Conclusion： Triptergium wilfordii had the similar relapse rate as azathioprine and similar adverse effects except for menstrual disorder. So triptergium wilfordii may be one of ways for maintenance therapy of lupus patients.