Mycophenolate Mofetil versus Cyclophosphamide for Initial Therapy in Childhood-Onset Proliferative Lupus Nephritis

Key Points The total renal response rate in the mycophenolate mofetil group was found to be noninferior to that in the cyclophosphamide group. There was no significant difference in the incidence of adverse drug reactions between the mycophenolate mofetil and cyclophosphamide groups. The reduction in SLE Disease Activity Index scores was similar between the two groups. Background Recent studies suggest that oral mycophenolate mofetil (MMF) may be similar to intravenous cyclophosphamide in treating lupus nephritis. However, these therapies have not been prospectively compared in childhood-onset lupus nephritis. Methods In this prospective, multicenter, randomized trial, patients aged 5–17 years with proliferative lupus nephritis (class 3/4±5) and severely increased proteinuria (urine protein-creatinine ratio ≥1000 mg/g and/or 24-hour urinary protein excretion >25 mg/kg) were randomly assigned to receive either MMF or intravenous cyclophosphamide as initial therapy, alongside glucocorticoids. The primary end point was total renal response (TRR) at 24 weeks, with the aim of demonstrating the noninferiority of MMF compared with intravenous cyclophosphamide, using a noninferiority margin of 12%. TRR encompassed complete renal response, primary efficacy renal response, and partial renal response. Secondary end points assessed systemic disease activity and safety. Results A total of 107 patients were enrolled from 17 hospitals, with 52 assigned to the MMF group (47 completed the 24-week therapy) and 55 assigned to the cyclophosphamide group (48 completed the 24-week therapy). In the intention-to-treat population, the TRR rate was 92% in the MMF group and 89% in the cyclophosphamide group (test for noninferiority, P = 0.008). In the per-protocol population, renal response was observed in 96% of patients in the MMF group versus 94% of patients in the cyclophosphamide group (test for noninferiority, P = 0.009). The difference in TRR rate between the MMF and cyclophosphamide groups was 3% (95% confidence interval, −9% to 15%) in the intention-to-treat population and 2% (95% confidence interval, −9% to 13%) in the per-protocol population. There were no significant differences in the incidence of adverse drug reactions between the MMF and cyclophosphamide groups in the intention-to-treat population (10% versus 15%, continuity correction chi-squared test, P = 0.44). Conclusions After 24 weeks of therapy, oral MMF was noninferior to intravenous cyclophosphamide as initial therapy for childhood-onset proliferative lupus nephritis and exhibited a similar safety profile. Clinical Trial registry name and registration number: MMF versus cyclophosphamide in the Induction Therapy of Pediatric Active Proliferative lupus nephritis, ClinicalTrials.gov, NCT05495893.