Maintenance therapies for proliferative lupus nephritis: mycophenolate mofetil,azathioprine and intravenous cyclophosphamide

Abstract

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.