Single infusion of rituximab for persistent steroid-dependent minimal-change nephrotic syndrome after long-term cyclosporine

Abstract

Rituximab (RTX) has been successfully used as a rescue therapy in children with steroid-dependent nephrotic syndrome (SDNS). However, little is known regarding maintenance therapy after a successful response to RTX in such patients. The efficacy and safety of a single RTX infusion (375 mg/m(2)) were assessed in ten patients who had persistent SDNS associated with minimal-change disease (MCD) despite the long-term use of cyclosporine (CsA). The mean follow-up after RTX infusion was 17 months. Applying RTX resulted in a significant reduction in the mean prednisolone (PSL) dose from 0.39 +/-0.18 to 0.15 +/- 0.14 mg/kg per day. The mean 12-month relapse rates significantly decreased from 4.1 +/- 1.7 to 0.6 +/- 0.6. All but one patient who had continued CsA as maintenance therapy after a single RTX infusion were able to withdraw from PSL without any relapses during the study period, whereas the remaining five patients who discontinued CsA experienced relapses after CD19 cells re-emerged, leading to the reintroduction of CsA or an additional RTX infusion. Infusion reactions occurred in five of ten patients. These data indicate that a single RTX infusion may improve response to CsA in patients with persistent SDNS due to the phenomenon of secondary resistance to CsA.

Rituximab-based novel strategies for the treatment of immune-mediated glomerular diseases

“…While the underlying pathophysiology is still being actively investigated, T-cell dysfunction and various permeability factors have been implicated in the pathogenesis [78], [79] and [80]. RTX has been used with some success in children with steroid-dependent idiopathic nephrotic syndrome, as shown in several case reports [81], [82], [83] and [84]. A randomized clinical trial of 54 children with steroid-and calcineurin inhibitordependent nephrotic syndrome treated with RTX versus standard therapy showed that proteinuria decreased by 70% more in the RTX arm [85].…”

A distinct lymphocyte distribution in relapse after rituximab for steroid-dependent nephrotic syndrome

“…There have been many reports recently of the steroid-sparing effect of RTX in NS [4][5][6][7][8], suggesting that not only T cells but also B cells may play a role in the pathogenesis of NS. The mechanism of RTX action in NS treatment is also unclear.…”

“…It has been reported that a single infusion of RTX can delete B cells for only about 5 months [4][5][6][7][8]. Thus, the establishment of a proper treatment protocol, such as the number of RTX infusions, timing of the introduction of RTX, and how to taper the PSL dose, is desired.…”

“…The monoclonal anti-CD20 antibody rituximab (RTX) is a novel therapy for childhood SDNS [4][5][6][7][8]. Significant decreases in the frequency of relapse, period of steroid use, and steroid dosages have been documented in patients following RTX administration.…”

“…Significant decreases in the frequency of relapse, period of steroid use, and steroid dosages have been documented in patients following RTX administration. However, NS relapse frequently occurs a few months after CD19 recovery [4][5][6][7][8], leading to the proposal that maintenance therapy with an immunosuppressant, such as MMF, is required to prevent relapse after RTX therapy [4].…”