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Mycophenolate mofetil as induction and maintenance therapy for lupus nephritis: rationale and protocol for the randomized, controlled Aspreva Lupus Management Study (ALMS)

Aspreva Pharmaceuticals Corp, Victoria, BC, Canada

G. Appel

Columbia University, 2960 Broadway NY 10027-6900, USA

M.A. Dooley

University of North Carolina, Chapel Hill, NC 27599, USA

E. Ginzler

SUNY-Downstate Medical Center, Brooklyn, NY, USA

D. Isenberg

University College, Gower Street, London, WC1E 6BT, UK

D. Jayne

Addenbrooke's Hospital, Cambridge, UK

D. Wofsy

University of California, San Francisco, CA 94143, USA

N. Solomons

Aspreva Pharmaceuticals Corp, Victoria, BC, Canada, nsolomons{at}aspreva.com

The Phase III Aspreva Lupus Management Study (ALMS) will investigate mycophenolate mofetil (MMF) therapy for lupus nephritis (LN). Eligibility criteria include: 12—75 years of age; diagnosis of systemic lupus erythematosus according to revised American College of Rheumatology criteria; and biopsy-demonstrated LN (Class III—V). Randomized patients will receive open-label induction therapy with MMF or cyclophosphamide in combination with corticosteroids for 24 weeks. The primary efficacy endpoint is treatment response [decreased proteinuria and stabilized (within 25% of baseline) or improved serum creatinine level]. Patients achieving response or complete remission (normalization of all parameters) will be rerandomized to double-blind, placebo-controlled maintenance treatment with MMF or azathioprine, both plus corticosteroids. The maintenance phase primary endpoint is time to treatment failure. To detect a 15% rate improvement in the MMF group compared with cyclophosphamide, and to provide 90% power, a total of 358 patients will be required for the induction phase. On the basis of a projected 278 rerandomized patients, the maintenance phase will have 90% power to detect a difference between treatment groups assuming azathioprine and MMF three-year failure rates of 59.5% and 40.7%, respectively. Aspreva Lupus Management Study may provide invaluable comparative data on the efficacy and safety of MMF as LN induction and maintenance therapy. Lupus (2007) 16, 972—980.

Key Words: ALMS • CellCept® • lupus nephritis • mycophenolate mofetil

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Lupus, Vol. 16, No. 12, 972-980 (2007)
DOI: 10.1177/0961203307084712


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