Cyclophosphamide for the treatment of systemic lupus erythematosus

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Abstract
Aggressive immunosuppressive therapy with cyclophosphamidehas 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-upof 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 managementofsevere or refractory to standard therapy neuropsychiatric,pulmonary, cardiovascular and hematologic disease. Pulsecyclophosphamide is associated with an increased risk for herpes zoster 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 flare 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 low-dose cyclophosphamide in combination with nucleoside analogs or biologic response modifiers.