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Evidence summaries

Non-Corticosteroid Treatment for Steroid-Sensitive Nephrotic Syndrome in Children

In children with frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS), rituximab used alone or with prednisone and calcineurin inhibitors (CNI) compared with placebo, prednisone or CNI and prednisone appears to reduce the risk of relapse. Level of evidence: "B"

The quality of evidence is downgraded by study limitations (unclear allocation concealment).

Summary

A Cochrane review [Abstract] 1 included 43 studies with a total of 2 428 children. The aim of the review was to evaluate the benefits and harms of non-corticosteroid immunosuppressive medications in steroid-sensitive nephrotic syndrome (SSNS) in children with a relapsing course of SSNS and in children with their first episode of nephrotic syndrome.

Rituximab (in combination with calcineurin inhibitors (CNI) and prednisolone) versus CNI and prednisolone reduced the number of children who relapse at 6 months (RR 0.23, 95% CI 0.12 to 0.43; 5 studies, n=269) and 12 months (RR 0.63, 95% CI 0.42 to 0.93; 3 studies, n=198). At 6 months, rituximab resulted in 126/1000 children relapsing compared with 548/1000 treated with conservative treatments. Rituximab resulted in more infusion reactions (RR 5.83, 95% CI 1.34 to 25.29; 4 studies, n=252).

Oral or IV cyclophosphamide, oral chlorambucil, levamisole, cyclosporin, and rituximab substantially reduced the incidence of relapse in children with relapsing SSNS. MMF appeared to be as effective as cyclosporin. Levamisole had a favourable side effect profile and cost, though it is not available in some countries. There were limited differences in efficacy between different agents, but it is possible that further studies would alter this conclusion.

Comment: Rituximab has generally been well tolerated in short-term studies, but the potential long-term adverse effects of rituximab in childhood nephrotic syndrome remain unclear. Rituximab is likely to be used as a second or third-line corticosteroid-sparing agent until more long-term data on adverse effects accumulate.

    References

    • Larkins NG, Liu ID, Willis NS et al. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev 2020;(4):CD002290. [PubMed]

Primary/Secondary Keywords