Combined intravenous methotrexate and cyclophosphamide for refractory childhood lupus nephritis

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Abstract
Objective: To evaluate the efficacy and safety of combining monthly intravenous methotrexate (IV MTX) with monthly IV cyclophosphamide (CYTX; given on the same day) for the treatment of children who develop recurrent diffuse proliferative glomerulonephritis secondary to systemic lupus erythematosus during or after the standard 3 year course of IV CYTX. Methods: Five children were treated with nine monthly doses of IV CYTX (750–1000 mg/m2/month) and IV MTX (50–300 mg/m2/month) given on the same day. Their clinical and laboratory measurements were collected every other week throughout the nine months. Results: All children improved dramatically. SLEDAI scores decreased from an average of 13.8 to 4.4, mean (SD) serum creatinine level fell from 100 (60) to 80 (40) µmol/l, and serum albumin rose from 28 (11) g/l to 41 (6) g/l, while the mean (SD) C3 level increased from 0.5 (0.1) g/l to 0.9 (0.4) g/l. Clinical improvement persisted after 4 years’ follow up despite discontinuing MTX and CYTX after 9 months. The average daily dose of corticosteroids has been reduced from 27.6 mg/day at the start of treatment to 12.5 mg/day at follow up. Conclusion: Combined IV MTX and IV CYTX treatment effectively controls recurrent or refractory lupus nephritis in children with significant disease activity after treatment with IV CYTX alone.