霉酚酸酯分散片治疗狼疮性肾炎的疗效及安全性

Efficiency and safety of mycophenolate mofetil dispersible tablets in patients with proliferative lupus nephritis:an open-labeled pilot study

目的:前瞻性非对照观察激素联合霉酚酸酯(MMF)分散片诱导治疗III型及IV型狼疮性肾炎(LN)的疗效及不良反应。方法:经肾活检确诊为活动性III型及IV型LN患者采用激素联合MMF分散片(赛可平)诱导治疗。所有患者均先接受甲基泼尼松龙静脉冲击(0.5g/d×3d)治疗,继以口服泼尼松0.8mg(kg·d),4周后泼尼松逐渐减量。MMF起始剂量0.75～1.5g/d,根据霉酚酸(MPA)AUC0～12h调整MMF剂量,MPA AUC0～12h目标值为30～40mg·h/L,观察治疗6个月的疗效和不良反应。疗效主要指标为完全缓解率(定义为尿蛋白定量<0.4g/d,无活动性尿沉渣,血白蛋白≥35g/L,SCr正常)和部分缓解率(定义为尿蛋白和尿沉渣红细胞计数下降超过基础值的50%,血白蛋白≥30g/L,SCr稳定)。结果:共23例患者[女性19例,男性4例,平均年龄(32.5±10.9)岁]进入本研究,其中病理类型III型9例,IV型14例,20例为初治患者。MMF平均治疗剂量(1.13±0.40)g/d,相应MPA浓度(35.80±9.31)mg·h/L。诱导治疗6个月时11例(47.8%)完全缓解,11例(47.8%)部分缓解,总缓解率95.6%,其中III型完全缓解率(55.6%vs42.9%,P>0.05)和总缓解率(100%vs92.9%,P>0.05)高于IV型。不良反应包括带状疱疹3例(13.0%)、胃肠道症状1例(4.3%)及肝酶升高1例(4.3%),无一例并发肺部感染。结论:激素联合MMF分散片(赛可平)诱导治疗III及IV型LN有较高缓解率,无严重不良反应。监测MPA血药浓度有助于调整MMF剂量。

Objective：A prospective, non-controlled study to observe the clinical efficacy and safety of mycophe- nolate mofetil （MMF） dispersible tablets in the treatment of patients with class Ⅲ and class Ⅳ lupus nephritis. Methodology：Twenty-three patients with renal biopsy-proved active class Ⅲ and class Ⅳ lupus nephritis were enrolled in this study. All patients had urinary protein≥1. 0 g/24h, and serum creatinine 〈265.2 μmol/L. They were treated with corti- costeroids and MMF dispersible tablets （ Cycopin, Hangzhou Zhongmei Huadong Pharmaceutical Co. Ltd）. The starting dose of MMF was 1.0-1.5 g/d, MMF doses were then controlled by blood MPA concentration （ MPA-AUC0-12 h ） to get the target AUC level of 30-40 mg·h/L during the first three months of induction period. The primary efficacy parameter was the complete and partial remission rate at 6 months. Results：They were 19 females and 4 males with an average age of （32. 5 ±10. 9） years old. Renal histology showed class Ⅲ in 9 patients, and classs Ⅳ in 14 patients. The average dose of MMF was （ 1.13 ± 0. 40） g/d with MPA-AUC0-12 h level （35.80 ±9.31 ） mg·h/L. At the end of 6 months of induction therapy, 11 cases （47.8%） had complete remission, and 11 patients （47.8%） had partial remission, and the total remission rate was 95.6%. The patients in class Ⅲ had higher remission rate than that in class Ⅳ（complete remission rate 55.6% vs 42. 9% , P 〉0. 05, and total remission rate 100% vs 92. 9% , P 〉0. 05）. The adverse events including herpes zoster （ 13.0% ） , gastrointestinal symptom （4. 3% ） and elevation of liver enzymes （4. 3% ） were observed and no one developed pulmonary infection. Conclusion：Induction treatment with steroids and MMF dispersible tablets showed high re-mission rate for patients with class Ⅲ and Ⅳ lupus nephritis without severe side effects by concentration-controlled MMF doses.