Sequential therapies for proliferative lupus nephritis

Long-term therapy with cyclophosphamide enhances renal survival in patients with proliferative lupus nephritis; however, the beneficial effect of cyclophosphamide must be weighed against its considerable toxic effects.

Fifty-nine patients with lupus nephritis (12 in World Health Organization class III, 46 in class IV, and 1 in class Vb) received induction therapy consisting of a maximum of seven monthly boluses of intravenous cyclophosphamide (0.5 to 1.0 g per square meter of body-surface area) plus corticosteroids. Subsequently, the patients were randomly assigned to one of three maintenance therapies: quarterly intravenous injections of cyclophosphamide, oral azathioprine (1 to 3 mg per kilogram of body weight per day), or oral mycophenolate mofetil (500 to 3000 mg per day) for one to three years. The base-line characteristics of the three groups were similar, with the exception that the chronicity index was 1.9 points lower in the cyclophosphamide group than in the mycophenolate mofetil group (P=0.009).

During maintenance therapy, five patients died (four in the cyclophosphamide group and one in the mycophenolate mofetil group), and chronic renal failure developed in five (three in the cyclophosphamide group and one each in the azathioprine and mycophenolate mofetil groups). The 72-month event-free survival rate for the composite end point of death or chronic renal failure was higher in the mycophenolate mofetil and azathioprine groups than in the cyclophosphamide group (P=0.05 and P=0.009, respectively). The rate of relapse-free survival was higher in the mycophenolate mofetil group than in the cyclophosphamide group (P=0.02). The incidence of hospitalization, amenorrhea, infections, nausea, and vomiting was significantly lower in the mycophenolate mofetil and azathioprine groups than in the cyclophosphamide group.

For patients with proliferative lupus nephritis, short-term therapy with intravenous cyclophosphamide followed by maintenance therapy with mycophenolate mofetil or azathioprine appears to be more efficacious and safer than long-term therapy with intravenous cyclophosphamide.