Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases

Abstract

Several case reports suggest that rituximab (RTX) could be effective in steroid-dependent nephrotic syndrome, but RTX efficacy has not yet been studied in a series of patients. Safety and efficacy of RTX were assessed in a multicenter series of 22 patients aged 6.3-22 years with severe steroid-dependent nephrotic syndrome or steroid-resistant but cyclosporin-sensitive idiopathic nephrotic syndrome. Patients were treated with two to four infusions of RTX. Seven patients were nephrotic at the time of RTX treatment. Peripheral B cells were depleted in all subjects. Remission was induced in three of the seven proteinuric patients. One or more immunosuppressive (IS) treatments could be withdrawn in 19 patients (85%), with no relapse of proteinuria and without increasing other IS drugs. RTX was effective in all patients when administered during a proteinuria-free period in association with other IS agents. When relapses occurred, they were always associated with an increase in CD19 cell count. Adverse effects were observed in 45% of cases, but most of them were mild and transient. This study suggests that RTX could be an effective treatment for severe steroid-dependent nephrotic syndrome.

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].…”

Nephrotic syndrome and rituximab: facts and perspectives

“…This summary is based on five case reports and 22 patients enrolled in a prospective multicenter trial [9,[14][15][16][17][18]. Patients enrolled in this multicenter trial suffered from frequently relapsing nephrotic syndrome necessitating intensive immunosuppressive therapy, including glucocorticoids, calcineurin inhibitors, cyclophosphamide, levamisol, and MMF, which was either not effective in inducing lasting remission and/or associated with severe drug toxicity [17].…”