Safety of Rituximab Compared with Steroids and Cyclophosphamide for Idiopathic Membranous Nephropathy

J Am Soc Nephrol. 2017 Sep;28(9):2729-2737. doi: 10.1681/ASN.2016091022. Epub 2017 May 9.


Guidelines recommend steroid plus cyclical cyclophosphamide (St-Cp) therapy for patients with idiopathic membranous nephropathy at high risk of progression to ESRD. Rituximab (Rtx) may be a safer alternative. In this retrospective, observational cohort study, we compared time to any adverse event (primary outcome); serious or nonserious events; partial and complete remission of the nephrotic syndrome; and a composite of doubling of serum creatinine, ESRD, or death between 100 Rtx-treated patients and 103 patients who received daily St-Cp We monitored patients with standardized protocols and adjusted for baseline characteristics by Cox regression. Over a median follow-up of 40 months, the Rtx group had significantly fewer adverse events than the St-Cp group (63 versus 173; P<0.001), both serious (11 versus 46; P<0.001) and nonserious (52 versus 127; P<0.001). Cumulative incidence of any first (35.5% versus 69.0%; P<0.001), serious (16.4% versus 30.2%; P=0.002), or nonserious (23.6% versus 60.8%; P<0.001) event was significantly lower with Rtx Adjusted hazard ratios (95% confidence intervals) between Rtx and St-Cp groups were 0.27 (0.16 to 0.44) for any first adverse event, 0.32 (0.15 to 0.68) for serious adverse events, and 0.23 (0.13 to 0.41) for nonserious adverse events. Although the cumulative incidence of partial remission was lower in the Rtx group, rates of complete remission and the composite renal end point did not differ significantly between groups. Because of its superior safety profile, we suggest that Rtx might replace St-Cp as first-line immunosuppressive therapy in patients with idiopathic membranous nephropathy and nephrotic syndrome.

Keywords: adverse events; clinical epidemiology; cyclophosphamide; drug safety; membranous nephropathy; rituximab.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents / adverse effects*
  • Anti-Inflammatory Agents / therapeutic use
  • Creatinine / blood
  • Cyclophosphamide / adverse effects*
  • Cyclophosphamide / therapeutic use
  • Drug Therapy, Combination / adverse effects
  • Female
  • Glomerulonephritis, Membranous / drug therapy*
  • Humans
  • Immunologic Factors / administration & dosage*
  • Immunologic Factors / therapeutic use
  • Immunosuppressive Agents / adverse effects
  • Male
  • Methylprednisolone / adverse effects*
  • Methylprednisolone / therapeutic use
  • Middle Aged
  • Nephrotic Syndrome / drug therapy*
  • Retrospective Studies
  • Rituximab / adverse effects*
  • Rituximab / therapeutic use
  • Time Factors


  • Anti-Inflammatory Agents
  • Immunologic Factors
  • Immunosuppressive Agents
  • Rituximab
  • Cyclophosphamide
  • Creatinine
  • Methylprednisolone