Efficacy and safety of immunosuppressive medications for steroid-resistant nephrotic syndrome in children: a systematic review and network meta-analysis

Shaojun Li, Haiping Yang, Pengfei Guo, Xiaoxiao Ao, Junli Wan, Qiu Li, Liping Tan, Shaojun Li, Haiping Yang, Pengfei Guo, Xiaoxiao Ao, Junli Wan, Qiu Li, Liping Tan

Abstract

Background: Conventional meta-analyses and randomized controlled trials have shown inconsistent results regarding the efficacy of immunosuppressants for pediatric steroid-resistant nephrotic syndrome (SRNS).

Objective: To conduct a network meta-analysis aimed at evaluating the efficacy and safety of available immunosuppressive agents in pediatric patients with SRNS.

Study methods: MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE were searched on January 2017. Data from randomized controlled trials (RCTs) were included. The main outcomes analyzed were efficacy [number/portion with complete remission (CR), number/portion with partial remission (PR), and total number/portion in remission (TR)] and safety [adverse secondary event (ASE) rates].

Results: A meta-analysis of 18 RCTs showed that tacrolimus was more efficacious for achieving CR than intravenous (i.v.) cyclophosphamide, mycophenolate mofetil (MMF), oral cyclophosphamide, leflunomide, chlorambucil, azathioprine, and plaebo/nontreatment (P/NT), and more efficacious than i.v. cyclophosphamide, oral cyclophosphamide, and P/NT in terms of TR outcomes. Cyclosporin was associated with a greater CR rate than i.v. cyclophosphamide, MMF, oral cyclophosphamide, chlorambucil, azathioprine, or P/NT, and associated with a greater TR rate than i.v. cyclophosphamide, oral cyclophosphamide, or P/NT. MMF was found to be more efficacious than i.v. cyclophosphamide and oral cyclophosphamide in terms of TR.

Conclusions: Tacrolimus and cyclosporine may be preferred initial treatments for children with SRNS. MMF may be another option for this patient population. Further studies of the efficacy and safety of these three drugs in children with SRNS should be pursued.

Keywords: SRNS; immunosuppressant; multiple-treatments meta-analysis; pediatrics.

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest concerning this article.

Figures

Figure 1. Flowchart of included studies
Figure 1. Flowchart of included studies
Figure 2. Distribution of histopathologic diagnoses in…
Figure 2. Distribution of histopathologic diagnoses in included RCTs
Figure 3. Network of eligible efficacy and…
Figure 3. Network of eligible efficacy and safety comparisons
(A–D) The thickness of the lines reflects the number of studies being compared, and node size reflects the number of individuals treated with each pharmacotherapy.
Figure 4. Comparison of efficacy across drugs
Figure 4. Comparison of efficacy across drugs
OR with 95% CI of network meta-analysis for CR (A), PR (B), TR (C) and ASE (D).
Figure 5. Efficacy and safety outcome rankings
Figure 5. Efficacy and safety outcome rankings
CR (A), PR (B), TR (C) and ASE (D) rankings reflect the probability of being the best, second best, etc., treatment among the treatments compared.
Figure 6
Figure 6
Inconsistency in closed loops at CR (A) PR (B) and TR (C). Graph shows estimates of differences between direct and indirect estimates as represented by 95% CIs.
Figure 7. Summary of comparison-adjusted funnel plot…
Figure 7. Summary of comparison-adjusted funnel plot results for CR rate

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