Efficacy of mycophenolate mofetil versus cyclophosphamide in the management of childhood-onset lupus nephritis: a systematic review and meta-analysis

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), affecting up to one-third of pediatric SLE patients. Timely induction therapy is critical in proliferative LN to prevent progression to kidney failure or death. Intravenous cyclophosphamide (IVCP) has long been a standard induction agent, but its toxicity profile has prompted interest in mycophenolate mofetil (MMF) as a potentially safer alternative. However, data comparing the efficacy and safety of MMF versus IVCP in children are limited and inconclusive.

To systematically review and synthesise existing evidence comparing the efficacy and safety of MMF versus IVCP for induction therapy in pediatric patients with proliferative LN.

A comprehensive search was conducted in six electronic databases (PubMed, EMBASE, Web of Science, SCOPUS, CINAHL, and CENTRAL) on June 2, 2025. Reference lists of included articles were also manually screened.

We included randomised controlled trials and observational studies published in English that directly compared MMF and IVCP as induction therapies in pediatric patients with biopsy-proven proliferative LN. Studies were required to report at least one of the following outcomes: kidney remission (complete or partial), adverse events, kidney failure, or death.

Eligible participants were children aged ≤ 17 years with a diagnosis of proliferative LN based on the American College of Rheumatology (ACR) criteria. Interventions involved MMF plus corticosteroids versus IVCP plus corticosteroids, with comparable adjunctive therapies.

Authors independently screened articles, extracted data, and assessed study quality using the RoB2 tool for RCTs and the ROBINS-I tool for observational studies. A random-effects meta-analysis was conducted to estimate pooled risk ratios (RRs) for complete remission. Sensitivity analyses and funnel plots were used to assess robustness and publication bias.

Out of 1,633 screened records, seven studies met the inclusion criteria, six observational studies (n = 282) and one RCT (n = 24). Meta-analysis of the observational studies revealed no significant difference in complete remission between the MMF and IVCP groups (pooled RR: 1.01; 95% CI: 0.78–1.29; I² = 0%). The RCT reported similar findings, with remission rates of 70% (MMF) vs. 57.1% (IVCP) (p = 0.527). Adverse event rates were comparable, but IVCP showed more frequent non-infectious complications (e.g., leukopenia, hemorrhagic cystitis, alopecia). No deaths were reported.

The analysis was limited by the predominance of observational studies and only one small pediatric RCT with a high risk of bias. Variability in outcome definitions, inconsistent reporting of baseline disease severity, and lack of subgroup analysis limited further interpretation. Small study numbers precluded a formal assessment of publication bias.

The efficacy of MMF appears to be similar to IVCP for induction therapy in pediatric proliferative LN, with a potentially more favourable safety profile. These findings support MMF as a viable alternative to IVCP; however, robust, multicenter pediatric RCTs are urgently needed to establish definitive treatment recommendations and guide clinical practice.

PROSPERO: CRD42024533313 available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024533313

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