Efficacy and safety of mycophenolate mofetil versus cyclophosphamide for induction therapy of lupus nephritis: a meta-analysis of randomized controlled trials

Abstract

Introduction: Whether mycophenolate mofetil is superior to cyclophosphamide as induction therapy for lupus nephritis (LN) remains controversial.

Objective: Our objective was to investigate the efficacy and safety of mycophenolate mofetil compared with cyclophosphamide as induction therapy for LN patients.

Methods: Randomized controlled trials (RCTs) on humans were identified in searches of PubMed/MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (all to 1 December 2011). Studies that compared the efficacy and safety between mycophenolate mofetil and cyclophosphamide as induction therapy in LN patients were selected. Methodological quality of the included trials was assessed according to Cochrane criteria and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The fixed effects model was applied for pooling where there was no significant heterogeneity, otherwise the random effects model (Dersimonian and Laird method) was performed.

Results: Seven trials were identified, including 725 patients. The Dersimonian and Laird method was applied for renal remission in the presence of significant heterogeneity, and no statistically significant differences were distinguished between mycophenolate mofetil and cyclophosphamide. To explore the possible source of heterogeneity, meta-regression was performed. It was suggested that no obvious study- or patient-level factors could explain interstudy heterogeneity with statistical significance. Among all these factors, the mode of administration of cyclophosphamide could explain most of the heterogeneity, although the coefficient was insignificant. Therefore, we performed a sensitivity analysis by excluding the trial in which cyclophosphamide was administered orally instead of intravenously, which suggested that mycophenolate mofetil was more effective than intravenous cyclophosphamide for inducing complete remission (relative risk [RR] 1.72; 95% CI 1.17, 2.55; p = 0.006) and complete or partial remission (RR 1.18; 95% CI 1.04, 1.35; p = 0.01). In addition, mycophenolate mofetil was superior to cyclophosphamide for significantly reducing end-stage renal disease (ESRD) or death (RR 0.64; 95% CI 0.41, 0.98; p = 0.04). For the safety comparison, lower risks of leukopenia, amenorrhoea and alopecia, and a higher risk of diarrhoea were found with mycophenolate mofetil. No statistical differences in infection and gastrointestinal symptoms were distinguished between mycophenolate mofetil and cyclophosphamide. The relatively small number and the open-label fashion of eligible RCTs may limit the value of our meta-analysis.

Conclusions: Mycophenolate mofetil is superior to intravenous cyclophosphamide for inducing renal remission, and has a significant advantage over cyclophosphamide for reducing ESRD or death. Furthermore, mycophenolate mofetil has lower risks of leukopenia, amenorrhoea and alopecia, but a higher risk of diarrhoea than cyclophosphamide. However, our conclusions need to be proved further in larger well designed trials.