Corticosteroids Combined with Mycophenolate Mofetil vs. Corticosteroids Combined with Cyclophosphamide for Induction Therapy of Childhood-Onset Lupus Nephritis

Background: Lupus nephritis (LN) is one of the most common severe manifestations of systemic lupus erythematosus, yet the optimal induction treatment in pediatric patients remains undefined. This study examined the efficacy and safety of oral mycophenolate mofetil (MMF) combined with corticosteroid versus intravenous cyclophosphamide (CYC) combined with corticosteroid for induction treatment of childhood-onset LN. Methods: This was a multi-center, randomized, open-label, phase 3, non-inferiority trial including patients aged 5 to 18 years with a diagnosis of systemic lupus erythematosus and biopsy-proven class III/IV ± V LN and urinary protein levels greater than 1g per 24 hours. Patients were randomly assigned (1:1) to receive MMF or CYC combined with corticosteroids stratified by gender and pathological classification. The primary endpoint was complete remission at 6 months. To conclude the noninferiority of MMF, the lower bound of the two-sided 95% confidence interval for the difference in complete remission rate between the two groups must exceed the predefined noninferiority margin of 15%. This study is registered with Chinese Clinical Trial Registry (ChiCTR2100053545). Results: Between October 2021 and Feb 2025, 41 patients were enrolled at 4 study sites and randomized to receive either oral MMF (n=20) or intravenous CYC (n=21). At 6 months, the complete remission rate was higher in the MMF group compared with the CYC group (14 of 20 [70.0%] vs 10 of 21 [47.6%]), yielding an absolute difference of 22.4% (95% CI, -8.1 to 49.0; P = 0.006). Despite comparable incidences of adverse events reported between the two treatment groups, the number of AEs per patient in the CYC group was significantly higher than that in the MMF group (median [interquartile range], 2.00 [1.00 to 4.00] vs 1.00 [0 to 1.25]; P = 0.015). Infection and gastrointestinal symptoms were significantly more frequent among patients receiving CYC than MMF (infection: 15 of 21 [71.4%] vs 7 of 20 [35.0%]; P = 0.043; gastrointestinal symptoms: 6 of 21 [28.6%] vs 0 [0%]; P = 0.035). Conclusion: This trial demonstrated that oral MMF is an effective induction treatment for children with proliferative LN, with a favorable safety profile.