Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis.

Abstract

Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m(2) in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.

• Authors: Gerald B Appel, Gabriel Contreras, Mary Anne Dooley, Ellen M Ginzler, David Isenberg, David Jayne, Lei-Shi Li, Eduardo Mysler, Jorge Sánchez-Guerrero, Neil Solomons, David Wofsy, Aspreva Lupus Management Study Group
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 20 Issue 5 Pg. 1103-12 (May 2009) ISSN: 1533-3450 [Electronic] United States
• PMID: 19369404 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Cyclophosphamide
• Mycophenolic Acid

Topics

• Cyclophosphamide (administration & dosage, adverse effects, therapeutic use)
• Ethnicity
• Female
• Glomerular Filtration Rate
• Humans
• Immunosuppressive Agents (therapeutic use)
• Injections, Intravenous
• Lupus Nephritis (drug therapy, mortality, pathology)
• Male
• Mycophenolic Acid (adverse effects, analogs & derivatives, therapeutic use)
• Racial Groups
• Treatment Outcome