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Mycophenolate Mofetil for Induction Therapy of Lupus Nephritis: A Systematic Review and Meta-Analysis

Michael Walsh^*,, Matthew James^*, David Jayne, Marcello Tonelli^,||,¶, Braden J. Manns^*,,¶, and Brenda R. Hemmelgarn^*,

Departments of ^* Medicine and Community Health Sciences, University of Calgary, Calgary, and Departments of Medicine and ^|| Critical Care, University of Alberta, and ^¶ Institute of Health Economics, Edmonton, Alberta, Canada; and Renal Unit, Addenbrooke's Hospital, Cambridge, United Kingdom

Address correspondence to: Dr. Michael Walsh, Lupus and Vasculitis Clinic, Box 118, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, United Kingdom. Phone: +223-217-259; Fax: +223-586-796; E-mail: mwwalsh{at}ucalgary.ca

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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Role of Mycophenolate Mofetil in the Treatment of Lupus Nephritis

Gabriel Contreras and Jonathan Sosnov
Clin. J. Am. Soc. Nephrol. 2007 2: 879-882. [Full Text] [PDF]

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				I. Neumann, H. Fuhrmann, I-F. Fang, A. Jaeger, P. Bayer, and J. Kovarik Association between mycophenolic acid 12-h trough levels and clinical endpoints in patients with autoimmune disease on mycophenolate mofetil Nephrol. Dial. Transplant., November 1, 2008; 23(11): 3514 - 3520. [Abstract] [Full Text] [PDF]

				G. Contreras and J. Sosnov Role of Mycophenolate Mofetil in the Treatment of Lupus Nephritis Clin. J. Am. Soc. Nephrol., September 1, 2007; 2(5): 879 - 882. [Full Text] [PDF]