Efficacy and safety of leflunomide combined with pulse cyclophosphamide in treatment of severe and refractory lupus nephritis:a one year clinical trial

ZHANG Hong-feng; XIAO Wei-guo; HOU Ping; LI Shu-fan; WANG Xiao-fei

Abstract：Objective To assess efficacy and safety of leflunomide combined with pulse cyclophosphamide in the treatment of severe and refractory lupus nephritis(SRLN). Methods From Jan. 1999 to April 2009,a total of 42 SRLN patients(16 ～ 50 years old) were treated in our hospital. After induced therapy with cyclophosphamide (total dose not less than 6. 0 g) in combination with steroids,the patients showed no responsiveness : the proteinuria reduction was less than 10% ,or still more then 3. 5 g per day. The loading dose of leflunomide was 40 mg or 50mg once daily for the first 3 days,followed by maintenance dose of 40 mg or 50 mg twice weekly for two months, and then once a week,according to whether the body weight was less than 50 kg or not, whether the age was less than 18 years old or not, and disease severity, respectively. Pulse cyclophosphamide was intravenously given monthly for four times(0. 8 grams or 1.0 grams) ,then quarterly. All patients were prescribed oral prednisone 0. 8 ～ 1.0 mg/kg. Serum albumim, complement C3 and C4, systemic lupus erythematosus disease activity index(SLE-DAI) and proteinuria were investigated at study entry ,3 months,6 months and 12 months, respectively. Results Thirty-nine cases were followed up for 12 months. Serum complement C3 increased slowly at 3 months,but had no difference compared with before treatment(P > 0. 05), and increased quickly at 6 months and 12 months (P < 0. 01). Serum albumin,complement C4,SLEDAI and proteinuria were all significandy improved at 3 months,6 months and 12 months (P < 0. 01). Adverse events included inflammation (9 cases), nausea (4 cases), elevated liver enzymes (ALT or GGT,4 cases), hypertension (2 cases), leukocytopenia (2 cases) and thrombocytopenia (1 case). Conclusion Leflunomide shows good efficacy and mild adverse effects in combination with pulse cyelophosphamide in the treatment of SRLN patients. n