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Rheumatology Advance Access originally published online on June 3, 2009
Rheumatology 2009 48(8):944-952; doi:10.1093/rheumatology/kep120
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Mycophenolate mofetil is as efficacious as, but safer than, cyclophosphamide in the treatment of proliferative lupus nephritis: a meta-analysis and meta-regression

Anselm Mak1, Alicia A. C. Cheak1, Jason Y. S. Tan1, Hnin Cho Su1, Roger C. M. Ho2 and Chak Sing Lau3

1Division of Rheumatology, Department of Medicine, 2Department of Psychological Medicine, National University of Singapore, Singapore and 3Department of Medicine and Therapeutics, University of Dundee, Dundee, UK.

Correspondence to: Anselm Mak, Yong Loo Lin School of Medicine, National University of Singapore, Department of Medicine, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074. E-mail: mdcam{at}nus.edu.sg


  Abstract

Objective. Since mycophenolate mofetil (MMF) has emerged as an immunosuppressant for treating proliferative lupus nephritis, the role of cyclophosphamide (CYC)-containing regimens is being challenged. Efficacy data from randomized controlled trials (RCTs) and previous meta-analyses comparing these two agents for treating lupus nephritis have been inconsistent as they were heterogeneous in design and of small sample size. An updated meta-analysis is therefore required.

Methods. Publications in the English literature were searched with the keywords ‘mycophenoate’, ‘mycophenolic’, ‘lupus nephritis’, ‘nephritis’ and ‘glomerulonephritis’ for RCTs in electronic databases. Primary outcome was relative risk (RR) of renal remission at 6 months. Secondary outcome included RRs of mortality, development of end-stage renal failure (ESRF) and side effects. Meta-regression was performed to identify factors explaining the heterogeneity of the effect sizes.

Results. Ten eligible RCTs involving 847 patients were included. MMF offers similar efficacy in inducing renal remission as CYC (RR 1.052; 95% CI 0.950, 1.166) and the risks of death (RR 0.709; 95% CI 0.373, 1.347) and ESRF (RR 0.453; 95% CI 0.183, 1.121) were comparable. Significantly fewer patients receiving MMF developed amenorrhoea (RR 0.212; 95% CI 0.094, 0.479) and leucopenia (RR 0.473; 95% CI 0.269, 0.832) while the risks of herpes infection and pneumonia tended to be lower and that of diarrhoea appeared higher in the MMF groups. Meta-regression revealed that the non-white and non-Asian ethnicities contributed significantly to the heterogeneity of the effect sizes of renal remission.

Conclusion. MMF offers similar efficacy in renal remission and survival as CYC. MMF appears safer than CYC in the treatment of proliferative lupus nephritis.

KEY WORDS: Mycophenolate, Cyclophosphamide, Lupus, Nephritis, Meta-analysis, Meta-regression

Submitted 10 November 2008; revised version accepted 15 April 2009.
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