吗替麦考酚酯联合糖皮质激素治疗狼疮性肾炎的疗效及安全性:开放性多中心研究

Efficacy and Safety of Treatment with Combine Mycophenolate Mofetil and Corticosteroid for Lupus Nephritis:A Multicenter Open-label Study

目的探讨吗替麦考酚酯联合糖皮质激素治疗狼疮性肾炎的疗效及安全性。方法采用随机开放多中心研究。所有入选患者均符合1997年美国风湿病学会(ACR)修订的系统性红斑狼疮(systemic lupus erythematosus, SLE)诊断标准,同时伴有肾脏受累。患者服用国产吗替麦考酚酯(顺友)分散片,体重>60 kg者,2.0 g/d;体重≤60 kg者,1.5 g/d,均分两次服用。泼尼松的起始剂量为1.0 mg/(kg·d),共6周,以后每2周减量5%～10%,治疗第6个月时将泼尼松控制在维持剂量10～15 mg/d;复发病例以及其他器官稳定但有肾炎活动的SLE患者维持原激素用量。观察指标包括狼疮活动指数(SLE-DAI)、24小时尿蛋白定量、血清白蛋白水平、肾功能、抗ds-DNA和补体C3、复发率、患者存活率、感染发生率及其他不良反应(包括胃肠道反应、白细胞减少、血小板下降、肝功能损害和脱发等)。结果入选27例患者治疗后SLE-DAI、24小时尿蛋白定量、血清白蛋白、尿素氮及血沉(ESR)均较治疗前明显改善,且改善程度与治疗时间呈正相关,差别有统计学意义。两药联合治疗3个月的缓解率为74.1%,6个月的缓解率为88.9%。7例(25.9%)患者发生12人次不良事件,不良反应大都轻微,继续服药可自行消失。27例患者均存活,存活率为100%。结论吗替麦考酚酯对SLE具有独特的疗效和良好的安全性,特别适用于难治性和不耐受传统细胞毒药物的狼疮性肾炎。

Objective To evaluate the efficacy and safety of therapy with combined mycophenolate mofetil （Shunyou） dispersible tablet and corticosteriod for lupus nephritis. Methods A randomized open-label multicenter study were performed. All enrolled patients have lupus nephritis and fulfill 1997 revised American College of Rheumatology SLE criteria. Patients were taking Shunyou dispersible tablet 2.0 g/d, if body weight was equal or more than 60 kg, or 1.5 g/d, if body weight was less than 60 kg. For new cases the initial dosage of prednisone was 1.0 mg/（kg.d） for 6 weeks, then tapered 5%- 10% every 2 weeks till 6 months, then remained at 10-15mg/d; recurrent cases and cases with a otherwise stable disease except active lupus nephritis maintained their original prednisone dosage. Clinical and laboratory parameters including SLEDAI, 24 hours urine anti-dsDNA, C3, relapse rate, patient survival rate, incide gastrointestinal reactions, neutropenia, thrombocytopenia, protein, serum albumin, renal function, nce of infection, other side-effect including liver damage, hair loss were observed. Results A total of 27 patients were enrolled and completed the course in this muhisite study. Compared with baseline data, SLEDAI, 24-hour urine protein r（g/d） from the four weeks after treatment, serum albumin and blood urea nitrogen from the eight weeks after treatment, ESR） from the 12 weeks after treatment showed a marked improvement, with the extension of the treatment time, the improvement became more and more obvious, the difference was statistically significant. Seven patients （25.9%） had total 12 adverse events, most of these adverse reaction were mild and went away with continua- tion of medication. Conclusion Clinical study has confirmed that Shunyou dispersible tablet has unique efficacy and good safety for SLE, especially for lupus nephritis that is refractory and/or intolerance to cytotoxic drugs.