Efficacy and acceptability of immunosuppressive agents for pediatric frequently-relapsing and steroid-dependent nephrotic syndrome: A network meta-analysis of randomized controlled trials

Medicine (Baltimore). 2019 May;98(22):e15927. doi: 10.1097/MD.0000000000015927.

Abstract

Introduction: A network meta-analysis was conducted to regard the effects of available immunosuppressive medications in pediatric frequently-relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS).

Methods: We reviewed systematically 26 randomized controlled trials (1311 patients) that compared any of the following immunosuppressive agents to placebo/nontreatment (P/NT) or another drug for FRNS/SDNS treatment in children.

Results: The main outcomes were efficacy and acceptability. At the 6-month, cyclophosphamide, chlorambucil, levamisole, and rituximab had better efficacy than P/NT (odds ratio [OR]: 0.09, 0.03, 0.28, and 0.07, respectively); cyclophosphamide was significantly more effective than azathioprine and chlorambucil. At 12 months, cyclophosphamide, chlorambucil, cyclosporine, levamisole, and rituximab had better efficacy than P/NT (0.10, 0.03, 0.10, 0.23, and 0.07, respectively); Chlorambucil were found to be more efficacious than levamisole and MMF (0.12 and 0.09, respectively). At 24 months, cyclophosphamide, chlorambucil, and levamisole had better efficacy than P/NT (0.09, 0.04, and 0.03, respectively); cyclophosphamide had better efficacy than cyclosporine and vincristine (0.17 and 0.39, respectively).

Conclusion: No significant differences in acceptability were found. Our results suggest that cyclophosphamide may be preferred initially in children with FRSN/SDNS, chlorambucil, and rituximab may be acceptable medications for patients with FRSN/SDNS. Long-term follow-up trials focused on gonadal toxicity and limitation of maximum dosage of cyclophosphamide should been carried out.

Publication types

  • Meta-Analysis

MeSH terms

  • Adolescent
  • Azathioprine / therapeutic use
  • Child
  • Child, Preschool
  • Chlorambucil / therapeutic use
  • Cyclophosphamide / therapeutic use
  • Cyclosporine / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / therapeutic use*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Infant
  • Levamisole / therapeutic use
  • Male
  • Nephrotic Syndrome / drug therapy*
  • Network Meta-Analysis
  • Randomized Controlled Trials as Topic
  • Recurrence
  • Rituximab / therapeutic use
  • Secondary Prevention / methods
  • Treatment Outcome

Substances

  • Glucocorticoids
  • Immunosuppressive Agents
  • Chlorambucil
  • Levamisole
  • Rituximab
  • Cyclosporine
  • Cyclophosphamide
  • Azathioprine