Comparative Efficacy and Safety of Mycophenolate Mofetil Versus Cyclophosphamide As Induction Therapy for Lupus Nephritis: A Systematic Review and Meta-Analysis

Lupus nephritis (LN) is a serious and potentially fatal systemic lupus erythematosus complication that causes substantial morbidity and may progress to end-stage kidney disease. Traditionally, cyclophosphamide (CYC) has been prescribed as induction therapy for LN. However, there has been a trend toward using mycophenolate mofetil (MMF) as an alternative treatment due to concerns of toxicity. This systematic review and meta-analysis evaluated the comparative safety and efficacy of MMF to CYC as induction therapy in LN. PubMed, Embase, Scopus, and Cochrane CENTRAL databases were searched comprehensively from their inception through January 2026. Randomized controlled trials and observational studies comparing MMF and CYC in adult or pediatric patients with LN were included. Complete renal remission, partial renal remission, overall renal response, mortality, infections, GI adverse events, leukopenia, menstrual disorders, and alopecia were evaluated as outcomes. Overall, 12 studies involving 1,502 patients were analyzed. MMF was significantly associated with a higher rate of complete renal remission than CYC (risk ratio (RR) = 1.11, 95% confidence interval (CI): 1.01-1.22). No significant difference between the two therapies in partial renal remission, total renal response, mortality, infection, GI adverse events, or leukopenia. However, MMF was associated with significantly lower risks of menstrual disorders (RR = 0.47, 95% CI: 0.27-0.82) and alopecia (RR = 0.32, 95% CI: 0.15-0.70). Overall, MMF appears to be as effective as CYC for the induction treatment of LN, while exhibiting a more favorable safety profile regarding reproductive and cosmetic adverse events. The results indicate that MMF is an effective and safer induction agent for patients with LN.