Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial

Arthritis Rheum. 2010 Jan;62(1):211-21. doi: 10.1002/art.25052.

Abstract

Objective: To assess the effect of mycophenolate mofetil compared with intravenous pulses of cyclophosphamide on the nonrenal manifestations of lupus nephritis.

Methods: Patients with active lupus nephritis (renal biopsy class III, IV, or V) were recruited for the study (n = 370) and treated with mycophenolate mofetil (target dosage 3 gm/day) or intravenous cyclophosphamide (0.5-1.0 gm/m(2)/month), plus tapered prednisone, for 24 weeks. Nonrenal outcomes were determined using measures of whole body disease activity, including the British Isles Lupus Assessment Group (BILAG) disease activity index, the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and immunologic variables.

Results: Both treatments were effective on whole body disease activity in the systems examined, as indicated by changes in the classic BILAG index. With either treatment, remission was induced, notably in the mucocutaneous, musculoskeletal, cardiovascular/respiratory, and vasculitis systems, and flares were rare, as measured by the SELENA-SLEDAI. Levels of complement C3, C4, and CH50 and titers of anti-double-stranded DNA antibodies were normalized after treatment with either mycophenolate mofetil or intravenous cyclophosphamide.

Conclusion: In addition to the efficacy of both treatments on the renal system, this analysis showed that remission could also be induced in other systems. There was no clear difference in efficacy between mycophenolate mofetil and intravenous cyclophosphamide in ameliorating either the renal or nonrenal manifestations. Mycophenolate mofetil is, therefore, a suitable alternative to cyclophosphamide for the treatment of renal and nonrenal disease manifestations in patients with biopsy-proven lupus nephritis.

Trial registration: ClinicalTrials.gov NCT00377637.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antibodies, Antinuclear / blood
  • Antibodies, Antinuclear / drug effects
  • Complement System Proteins / analysis
  • Complement System Proteins / drug effects
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use*
  • Injections, Intravenous
  • Lupus Nephritis / diagnosis
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / physiopathology
  • Male
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Prednisone / therapeutic use
  • Prospective Studies
  • Remission Induction
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Antinuclear
  • Glucocorticoids
  • Immunosuppressive Agents
  • Cyclophosphamide
  • Complement System Proteins
  • Mycophenolic Acid
  • Prednisone

Associated data

  • ClinicalTrials.gov/NCT00377637