Rituximab in steroid-sensitive nephrotic syndrome: lessons from clinical trials

Kazumoto Iijima,Mayumi Sako,Kandai Nozu,Koichi Kamei

doi:10.1007/s00467-017-3746-9

Abstract

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. A total of 80–90% of patients with childhood idiopathic nephrotic syndrome achieve remission with steroid therapy [steroid-sensitive nephrotic syndrome (SSNS)]. However, approximately 50% of children with SSNS develop frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Children with FRNS or SDNS are usually treated with immunosuppressive agents, but 10–20% of children receiving immunosuppressive agents still show frequent relapses or steroid dependence during or after treatment, defined as complicated FRNS or SDNS. Rituximab, a chimeric anti-CD20 monoclonal antibody that was originally developed to treat patients with B-cell non-Hodgkin’s lymphoma, is currently used for treating SSNS. In this review we highlight recent studies, mainly randomized controlled trials of rituximab for SSNS, including complicated and uncomplicated forms of FRNS or SDNS in children. We also discuss the effects of these studies on the management of patients suffering from these conditions.

Highlights

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children, occurring in two of 100,000 children per year in Caucasians [1]
The results showed that proteinuria at 3 months after treatment was 70% lower in the rituximab arm [95% confidence interval (CI) 35–86%] than in the standard therapy arm
No patients in either group experienced Grade 3 or 4 infusion reactions. These findings indicate that rituximab is a safe and effective therapy, at least for 1 year, for childhoodonset, complicated frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS)

Summary

Introduction

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children, occurring in two of 100,000 children per year in Caucasians [1]. Smith reported that a boy suffering from complicated FRNS/SDNS for longer than 11 years achieved 10 months of remission after a single rituximab infusion [15] Following those case reports, Guigonis et al reported a multicenter case series (n = 22) including patients who received two to four doses of rituximab as treatment of severe steroid- or cyclosporine-dependent nephrotic syndrome (complicated SDNS) [16]. A case series by Ito et al suggested that maintenance therapy with MMF after rituximab administration was effective for maintaining long-term remission in children with complicated FRNS/SDNS [42] These findings led to a multicenter, double-blind, randomized, placebo-controlled trial (JSKDC07; Clinical Trials Registry ID: UMIN000014347) being conducted by the Japanese Study Group of Kidney Disease in Children (JSKDC).

Conclusions

Findings

Compliance with ethical standards