Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis

• Published in: Journal of the American Society of Nephrology Vol. 20; no. 5; pp. 1103 - 1112
• Main Authors: APPEL, Gerald B, CONTRERAS, Gabriel, WOFSY, David, DOOLEY, Mary Anne, GINZLER, Ellen M, ISENBERG, David, JAYNE, David, LI, Lei-Shi, MYSLER, Eduardo, SANCHEZ-GUERRERO, Jorge, SOLOMONS, Neil
• Format: Journal Article Web Resource
• Language: English
• Published: Washington, DC American Society of Nephrology 01.05.2009
• Subjects: Biological and medical sciences; Clinical Research; Continental Population Groups; Cyclophosphamide; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Cyclophosphamide - therapeutic use; Ethnic Groups; Female; Glomerular Filtration Rate; Human health sciences; Humans; Immunosuppressive Agents; Immunosuppressive Agents - therapeutic use; Injections, Intravenous; Kidneys; Lupus Nephritis; Lupus Nephritis - drug therapy; Lupus Nephritis - mortality; Lupus Nephritis - pathology; Male; Medical sciences; mycophenolate mofetil; Mycophenolic Acid; Mycophenolic Acid - adverse effects; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - therapeutic use; Nephrology. Urinary tract diseases; Rheumatology; Rhumatologie; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sciences de la santé humaine; Treatment Outcome; Urinary system involvement in other diseases. Miscellaneous; Antineoplastic agent; Skin disease; Nephrology; Autoimmune disease; Lupus nephritis; Urology; Systemic lupus erythematosus; Systemic disease; Kidney disease; Immunopathology; Connective tissue disease; Urinary system disease; Enzyme; IMP dehydrogenase; Enzyme inhibitor; Induction treatment; Immunomodulator; Alkylating agent; Oxazaphosphinane derivatives; Cyclophosphamide; Nitrogen mustard; Oxidoreductases; Immunosuppressive agent; Mycophenolate mofetil; Comparative study
• ISSN: 1046-6673; 1555-905X; 1555-9041; 1533-3450
• DOI: 10.1681/asn.2008101028

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.