Comparison of low-dose intravenous cyclophosphamide with oral mycophenolate mofetil in the treatment of lupus nephritis

Kidney Int. 2016 Jan;89(1):235-42. doi: 10.1038/ki.2015.318. Epub 2016 Jan 4.


No previous study has compared mycophenolate mofetil (MMF) with low-dose cyclophosphamide (CYC) in the treatment of lupus nephritis (LN). To do so, we recruited patients with LN (class III, IV, or V) and randomized them to receive either low-dose CYC or oral MMF. Those with crescentic LN, a serum creatinine over 265 μmol/l, and neurological or pulmonary lupus were excluded. MMF was prescribed at daily doses of 1.5-3 g for 24 weeks, while CYC was administered as six fortnightly infusions of 500 mg each. All patients received three methylprednisolone injections, followed by oral corticosteroids. Maintenance therapy with azathioprine and low-dose corticosteroid was started at end of induction therapy. The primary end point was treatment response at 24 weeks, while secondary end points were complete remission, Systemic Lupus Erythematosus Disease Activity Index and adverse events. Of the 173 patients recruited, 100 were equally randomized to receive either CYC or MMF. Baseline characteristics were similar, except for higher 24 h proteinuria in the CYC group. At 24 weeks, 37 patients in each group achieved the primary end point. The complete remission rate was 50% in CYC and 54% in MMF group. Gastrointestinal symptoms were significantly more frequent in patients receiving MMF (52 vs. 4%). However, other adverse events were similar. Thus, low-dose intravenous CYC is comparable in safety and efficacy to oral MMF in the induction treatment of less severe LN.

Keywords: cyclophosphamide; lupus nephritis; mycophenolate mofetil.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravenous
  • Administration, Oral
  • Adolescent
  • Adult
  • Anti-Inflammatory Agents / therapeutic use
  • Azathioprine / therapeutic use
  • Cyclophosphamide / administration & dosage*
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / economics
  • Drug Costs
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / economics
  • Induction Chemotherapy / adverse effects
  • Induction Chemotherapy / methods*
  • Lupus Nephritis / drug therapy*
  • Maintenance Chemotherapy
  • Male
  • Methylprednisolone / therapeutic use
  • Mycophenolic Acid / administration & dosage*
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / economics
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult


  • Anti-Inflammatory Agents
  • Immunosuppressive Agents
  • Cyclophosphamide
  • Mycophenolic Acid
  • Azathioprine
  • Methylprednisolone