2007Clinical Journal of the American Society of NephrologyRequires access

Mycophenolate Mofetil for Induction Therapy of Lupus Nephritis

Michael Walsh, Matthew T. James, David Jayne, Marcello Tonelli, Braden Manns, Brenda R. Hemmelgarn

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Abstract

BACKGROUND AND OBJECTIVES: Although the accepted standard of care for induction of lupus nephritis has been cyclophosphamide, recent trials suggest that mycophenolate mofetil may be as or more effective and less toxic. A systematic review and meta-analysis were performed to determine the risk for failure to induce remission of lupus nephritis in patients who were treated with mycophenolate mofetil compared with cyclophosphamide. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Studies were identified by a search of electronic databases, bibliographies, and conference proceedings and by contacting experts. Randomized trials that compared mycophenolate mofetil with cyclophosphamide for induction therapy in adults with biopsy-proven lupus nephritis were eligible. The primary outcome was failure to induce a remission of nephritis as defined by the original studies (based on proteinuria, renal function, and urine sediment). RESULTS: Four studies that included 268 patients and had homogeneous results across studies were identified. In a fixed-effects model, the pooled relative risk for failure to induce remission for mycophenolate mofetil compared with cyclophosphamide was 0.70. The relative risk for the composite outcome of death or end-stage renal disease for mycophenolate mofetil compared with cyclophosphamide was 0.44. Leukopenia and amenorrhea occurred more frequently in cyclophosphamide-treated patients. CONCLUSIONS: Treatment of lupus nephritis with mycophenolate mofetil compared with cyclophosphamide reduces the risk for failure to induce remission during induction therapy and may reduce the risk for death or end-stage renal disease. Mycophenolate mofetil may be considered as a first-line induction therapy for the treatment of lupus nephritis in patients without severe renal dysfunction.

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BACKGROUND AND OBJECTIVES: Although the accepted standard of care for induction of lupus nephritis has been cyclophosphamide, recent trials suggest that mycophenolate mofetil may be as or more effective and less toxic. A systematic review and meta-analysis were performed to determine the risk for failure to induce remission of lupus nephritis in patients who were treated with mycophenolate mofetil compared with cyclophosphamide. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Studies were identified by a search of electronic databases, bibliographies, and conference proceedings and by contacting experts. Randomized trials that compared mycophenolate mofetil with cyclophosphamide for induction therapy in adults with biopsy-proven lupus nephritis were eligible. The primary outcome was failure to induce a remission of nephritis as defined by the original studies (based on proteinuria, renal function, and urine sediment). RESULTS: Four studies that included 268 patients and had homogeneous results across studies were identified. In a fixed-effects model, the pooled relative risk for failure to induce remission for mycophenolate mofetil compared with cyclophosphamide was 0.70. The relative risk for the composite outcome of death or end-stage renal disease for mycophenolate mofetil compared with cyclophosphamide was 0.44. Leukopenia and amenorrhea occurred more frequently in cyclophosphamide-treated patients. CONCLUSIONS: Treatment of lupus nephritis with mycophenolate mofetil compared with cyclophosphamide reduces the risk for failure to induce remission during induction therapy and may reduce the risk for death or end-stage renal disease. Mycophenolate mofetil may be considered as a first-line induction therapy for the treatment of lupus nephritis in patients without severe renal dysfunction.

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Available abstract

BACKGROUND AND OBJECTIVES: Although the accepted standard of care for induction of lupus nephritis has been cyclophosphamide, recent trials suggest that mycophenolate mofetil may be as or more effective and less toxic. A systematic review and meta-analysis were performed to determine the risk for failure to induce remission of lupus nephritis in patients who were treated with mycophenolate mofetil compared with cyclophosphamide. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Studies were identified by a search of electronic databases, bibliographies, and conference proceedings and by contacting experts. Randomized trials that compared mycophenolate mofetil with cyclophosphamide for induction therapy in adults with biopsy-proven lupus nephritis were eligible. The primary outcome was failure to induce a remission of nephritis as defined by the original studies (based on proteinuria, renal function, and urine sediment). RESULTS: Four studies that included 268 patients and had homogeneous results across studies were identified. In a fixed-effects model, the pooled relative risk for failure to induce remission for mycophenolate mofetil compared with cyclophosphamide was 0.70. The relative risk for the composite outcome of death or end-stage renal disease for mycophenolate mofetil compared with cyclophosphamide was 0.44. Leukopenia and amenorrhea occurred more frequently in cyclophosphamide-treated patients. CONCLUSIONS: Treatment of lupus nephritis with mycophenolate mofetil compared with cyclophosphamide reduces the risk for failure to induce remission during induction therapy and may reduce the risk for death or end-stage renal disease. Mycophenolate mofetil may be considered as a first-line induction therapy for the treatment of lupus nephritis in patients without severe renal dysfunction.

Key concepts: Medicine, Mycophenolate, Lupus nephritis, Induction therapy, Mycophenolic acid, Systemic lupus erythematosus, Urology, Internal medicine

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