What is the role of cyclophosphamide in the treatment of lupus nephritis?

Updated: Feb 08, 2021
  • Author: Lawrence H Brent, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Both cyclophosphamide and azathioprine are effective in proliferative lupus nephritis, although cyclophosphamide is apparently more effective in preventing progression to ESRD. Mycophenolate mofetil has been shown to be at least as effective as intravenous (IV) cyclophosphamide, with less toxicity, in patients with focal or diffuse lupus nephritis who have stable renal function. [54, 55] It may be used alone [54, 55] or sequentially after a 6-month course of IV cyclophosphamide. [56]

Administer IV cyclophosphamide monthly for 6 months and every 2-3 months thereafter, depending on clinical response. The usual duration of therapy is 2-2.5 years. Reduce the dose if the creatinine clearance is less than 30 mL/min. Adjust the dose depending on the hematologic response. [57, 58]  The gonadotropin-releasing hormone analog leuprolide acetate has been shown to protect against ovarian failure. [59]

Shorter courses and lower doses of IV cyclophosphamide are used currently, which reduces the overall toxicity of cyclophosphamide. Sequential therapy with monthly IV cyclophosphamide for 6 months followed by mycophenolate mofetil [56] or Euro-Lupus dosing, which is 500 mg of IV cyclophosphamide every 2 weeks for 3 months followed by azathioprine. [60]  Both of those regimens have been shown to be effective in proliferative lupus nephritis.

Appel et al studied 370 patients with lupus nephritis in a randomized open-label study and found no significant difference in clinical improvement was observed with mycophenolate mofetil compared with IV cyclophosphamide. [61] The study included induction and maintenance therapy, and both study groups received prednisone.

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