来氟米特对Ⅳ型及Ⅴ型狼疮肾炎的诱导维持治疗

Induction and maintenance treatment for type IV and type V lupus nephritis with leflunomide： a prospective study

目的观察来氟米特诱导和维持治疗Ⅳ型及Ⅴ型狼疮肾炎（LN）的疗效及安全性。方法单中心前瞻性临床研究。选取1个月内经病理证实的Ⅳ型及Ⅴ型狼疮肾炎患者，在使用激素的基础上随机人组分别使用来氟米特（口服30mg／d，LEF组）或环磷酰胺（静1g／月，CTX组）。6个月后，维持方案为LEF组续用LEF 20mg／d，CTX组续用CTX 1g／3月，两组泼尼松均使用5～10mg／d。评价治疗的安全性和有效性。结果共40例患者进入试验，其中LEF组19例，CTX组21例；LEF组17例、CTX组18例完成了诱导期治疗。LEF组诱导治疗总有效率达88．2％，完全缓解率为52．9％；CXT组治疗总有效率为72．2％，完全缓解率为44．4％；两组间差异无统计学意义。缓解的患者中，LEF组有7例进入维持期治疗，随访时间（18．6±6．5）月，未出现蛋白尿复发，其中3例进行了重复肾活检，结果显示肾脏病理类型均由重转轻，活动性指数下降，但慢性指数有所上升。CTX组有11例进入维持期治疗，随访时间（25．1±9．6）月，其中有3例在随访中蛋白尿复发。LEF组发生不良反应14例次，主要是感染，以带状疱疹多见。环磷酰胺组发生不良反应18例次，主要为感染和月经不调，组间比较差异无统计学意义。结论来氟米特联合激素诱导及维持治疗Ⅳ型及Ⅴ型LN疗效显著，患者耐受性良好。

Objective To evaluate the efficacy and safety of leflunomide （LEF） in induction and maintenance therapy of type Ⅳ and type Ⅴ lupus nephritis. Methods A prospective single-center controlled clinical trial was conducted. Patients with biopsy-confirmed type Ⅳ and type Ⅴ lupus nephritis in one month were recruited. Patients were given either LEF （LEF oral 30 mg/d） or cyclophosphamide （CTX Ⅳ 1 g/month） combined with prednisolone （40-60 mg/d, tapered to 10 mg/d）. After 6 months of induction therapy, 20 mg/d LEF and 1 g/3months CTX with prednisolone （5-10 mg/d） added respectively. Side effects were recorded and the efficacy and safety were evaluated. Results Forty patients were enrolled （19 in LEF group and 21 in CTX group）, and 5 patients withdrew due to adverse events （2 in LEF group and 3 in CTX group） during induction therapy. The total response rate was 88.2% in LEF group and 72.2% in CTX group respectively. Complete remission rate was 52.9% in LEF group and 44.4% in CTX group after 6 months induction therapy respectively. There was no difference in the change of proteinuria, serum albumin, serum creatinine, C3 and SLEDAI between two groups. Eighteen response patients entered maintenance therapy （7 in LEF group, 11 in CTX group）. LEF group was followed up for （18.6±6.5） months, and no patient was found relapse, and 3 patients received repeated renal biopsy, which showed the pathologic type was improved and the activity index decreased, but the chronic index increased slightly. CTX group was followed up for （25.1±9.6） months and 3 patients relapsed. Major adverse event in LEF group was infection, among which herpes zoster was the most common type. Major adverse events in CTX group were infection and amenorrhea . Conclusions LEF combined with steroid appears to be a safe and effective therapy within the induction and maintenance stage of the patients with type Ⅳ and Ⅴ LN. The long-term benefit of LEF needs to be confirmed by additional studies.