Cyclophosphamide for the treatment of systemic lupus erythematosus

Aggressive immunosuppressive therapy with cyclophosphamide has improved the outcome of major organ disease in lupus patients. Controlled trials have shown that pulse cyclophosphamide is the treatment of choice for patients with moderate to severe proliferative nephritis. Long-term follow-up of patients participating in these controlled trials suggests that combining pulse cyclophoshamide with pulse methylprednisolone increases efficacy but not toxicity. Retrospective case series have also shown that pulse cyclophosphamide therapy may be effective for the management of severe or refractory to standard therapy neuropsychiatric, pulmonary, cardiovascular and hematologic disease. Pulse cyclophosphamide is associated with an increased risk for herpes tester infections in the short term and with sustained amenorrhea in the long-term. Recent studies have also drawn attention to the lack of response (or incomplete response) and fare of lupus after an initial response. In an effort to circumvent these limitations, current investigations explore the therapeutic potential of high-dose, immunoablative cyclophosphamide therapy or tow-dose cyclophosphamide in combination with nucleoside analogs or biologic response modifiers.