Background Long-term therapy with cyclophosphamide enhancesrenal survival in patients with proliferative lupus nephritis;however, the beneficial effect of cyclophosphamide must be weighedagainst its considerable toxic effects.
Methods Fifty-nine patients with lupus nephritis (12 in WorldHealth Organization class III, 46 in class IV, and 1 in classVb) received induction therapy consisting of a maximum of sevenmonthly boluses of intravenous cyclophosphamide (0.5 to 1.0g per square meter of body-surface area) plus corticosteroids.Subsequently, the patients were randomly assigned to one ofthree maintenance therapies: quarterly intravenous injectionsof cyclophosphamide, oral azathioprine (1 to 3 mg per kilogramof body weight per day), or oral mycophenolate mofetil (500to 3000 mg per day) for one to three years. The base-line characteristicsof the three groups were similar, with the exception that thechronicity index was 1.9 points lower in the cyclophosphamidegroup than in the mycophenolate mofetil group (P=0.009).
Results During maintenance therapy, five patients died (fourin the cyclophosphamide group and one in the mycophenolate mofetilgroup), and chronic renal failure developed in five (three inthe cyclophosphamide group and one each in the azathioprineand mycophenolate mofetil groups). The 72-month event-free survivalrate for the composite end point of death or chronic renal failurewas higher in the mycophenolate mofetil and azathioprine groupsthan in the cyclophosphamide group (P=0.05 and P=0.009, respectively).The rate of relapse-free survival was higher in the mycophenolatemofetil group than in the cyclophosphamide group (P=0.02). Theincidence of hospitalization, amenorrhea, infections, nausea,and vomiting was significantly lower in the mycophenolate mofetiland azathioprine groups than in the cyclophosphamide group.
Conclusions For patients with proliferative lupus nephritis,short-term therapy with intravenous cyclophosphamide followedby maintenance therapy with mycophenolate mofetil or azathioprineappears to be more efficacious and safer than long-term therapywith intravenous cyclophosphamide.
Source Information
From the Dialysis Unit (G.C.) and the Electron Microscopy Unit (V.P.), Veterans Affairs Medical Center and University of Miami; and the Divisions of Nephrology (B.L., O.L., P.O., D.R.) and Rheumatology and Immunology (E.T.), University of Miami both in Miami.
Address reprint requests to Dr. Contreras at the Division of Nephrology, 1600 NW 10th Ave. R-126, Miami, FL 33136, or at gcontrer{at}med.miami.edu.
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