Geographical variation in the response of lupus nephritis to mycophenolate mofetil induction therapy

Clin Nephrol. 2011 Mar;75(3):233-41. doi: 10.5414/cnp75233.

Abstract

Objective: The induction therapy used in the management of Class III and IV lupus nephritis has been narrowed down to a choice between cyclophosphamide (CYC) and mycophenolate mofetil (MMF). However, there has been variability in the response to these agents, which may relate to demographic factors. In this study, we analyzed geographic factors affecting the response to CYC or MMF with a stratified meta-analysis.

Methods: We found and included 11 studies for our analyses--7 randomized controlled trials (RCTs) and 4 non-RCTs--that were stratified as being in Asia or elsewhere.

Results: Meta-analysis of Asian studies showed no difference between regimens (RR = 0.98, 95% CI 0.74-1.28, p = ns) and no heterogeneity. The 2 RCT's from outside Asia showed significant advantage of MMF as induction therapy (RR = 3.69, 95%CI 1.45-9.3, p < 0.01) without heterogeneity. Together there was significant heterogeneity (Q = 11.69, I2 = 57.2%, p < 0.05) suggesting that the overall heterogeneity results from a difference between these groups. We repeated this analysis with the multicenter ALMS trial with their reported ethnicity-specific data. Again, no significant heterogeneity was seen in either subgroup (Asian: Q = 2.08, I2 = 0%, p = ns; Others: Q = 4.49, I2 = 55.5%, p = ns). Studies from Asia did not show a significant improvement with the use of MMF (RR = 1.06, 95%CI 0.79-1.41, p = ns) while data from RCTs conducted outside Asia suggested a greater likelihood of complete remission with the use of MMF (RR = 1.85, 95%CI 1.03-3.29, p < 0.05).

Conclusion: Our analysis demonstrates a higher likelihood of complete remission with MMF in patients outside Asia.

Publication types

  • Meta-Analysis

MeSH terms

  • Asian Continental Ancestry Group / statistics & numerical data
  • Continental Population Groups / statistics & numerical data*
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / ethnology
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Remission Induction
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Cyclophosphamide
  • Mycophenolic Acid