For the treatment of proliferative
lupus nephritis, long-term
cyclophosphamide (CY) regimens are efficacious, however, at the expense of substantial toxicity. In the last decade, sequential regimens of short-term CY induction followed by either
mycophenolate mofetil (MMF) or
azathioprine (AZA) maintenance have shown to be efficacious and safe reducing the long-term exposure to CY. In a maintenance study including predominantly Hispanics and African-Americans, the patients who received MMF and AZA maintenance had a higher cumulative probability of remaining free of the composite of death or
chronic renal failure (CRF) compared to quarterly intravenous CY (IVCY) maintenance (89% in MMF, 80%, in AZA and 45% in IVCY). Likewise, MMF and AZA maintenance were associated with significantly lower incidence of severe
infections (2% in each MMF or AZA, and 25% in IVCY), sustained
amenorrhea (6% in MMF, 8% in AZA, and 32% in IVCY), and hospitalizations (one hospital-days per patient-year in each MMF or AZA, and 10 in IVCY). In a European induction study including predominantly Caucasians, patients who received any of two sequential regimens, low dose versus high dose IVCY induction both followed by AZA maintenance, had a high cumulative probability of remaining free of treatment failure (84% in low dose IVCY and 80% in high dose IVCY; treatment failure defined as a composite of free of
corticosteroid resistant flare,
nephrotic syndrome, doubling
creatinine, and persistent elevated
creatinine). Low dose IVCY and high dose IVCY induction were associated with low incidence of sustained
amenorrhea (4% in each group) and severe
infections (11% in low dose and 22% in high dose IVCY induction). Of interest, most of the severe
infection episodes occurred while patients were receiving IVCY induction. Finally an Asian study demonstrated that patients with proliferative
lupus nephritis could be effectively treated with short-term oral CY induction followed by AZA maintenance. The cumulative probability of complete remission was 76%. The relapse rate was only 11%. The incidence of permanent
amenorrhea and
infection were 8% and 33%, respectively. None of the Asian patients had an increase in serum
creatinine level to double the baseline value. Maintenance
therapies with MMF or AZA following short-term CY induction in a sequential regimen are efficacious and safe for the treatment of high-risk patients with proliferative
lupus nephritis.