Combined intravenous methotrexate and cyclophosphamide for refractory childhood lupus nephritis

Ann Rheum Dis. 2004 Mar;63(3):321-3. doi: 10.1136/ard.2003.008342.

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/m(2)/month) and IV MTX (50-300 mg/m(2)/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) micro mol/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.

MeSH terms

  • Blood Proteins / analysis
  • Chronic Disease
  • Complement C3 / analysis
  • Creatinine / blood
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use*
  • Drug Therapy, Combination
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Leukopenia / chemically induced
  • Lupus Nephritis / blood
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / immunology
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use*
  • Prednisone / therapeutic use
  • Serum Albumin / analysis

Substances

  • Blood Proteins
  • Complement C3
  • Immunosuppressive Agents
  • Serum Albumin
  • Cyclophosphamide
  • Creatinine
  • Prednisone
  • Methotrexate