Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children

Abstract

We conducted a multicenter prospective trial to evaluate the efficacy, safety and pharmacokinetics of a single dose of rituximab (375 mg/m(2) body surface area) for the treatment of children with refractory steroid-dependent nephrotic syndrome (SDNS). All patients (n = 12) were able to discontinue steroids at a median of 74 days after treatment. The frequency of relapses per 6 months was significantly reduced and the steroid-free period per 6 months was significantly increased after treatment compared with those before treatment. The condition in nine of the patients (75%) relapsed at a median of 129 days after treatment, and seven patients were given additional rituximab due to steroid dependency. Most of the relapses developed simultaneously with recovery of B-cells. However, three patients (25%) did not have a relapse with B-cell recovery and the disease was kept in remission for more than 1 year. None of the patients developed life-threatening adverse events. This is the first report of a prospective study of a single dose of rituximab for refractory SDNS. Treatment with a single dose of rituximab may be effective for refractory SDNS, but its efficacy to prevent relapses was transient in most of the patients.

Rituximab in Steroid-Dependent or Frequently Relapsing Idiopathic Nephrotic Syndrome

“…26 The pathogenic role of B lymphocytes would also explain why MCD or FSGS may occasionally occur in patients with other B cell-mediated diseases 27 and why NS remission achieved by rituximab associates with circulating B-cell depletion. [8][9][10][11][12][13][14]26 In patients in this study, persistence of remission after B lymphocyte reappearance in the circulation could actually be the result of a complete and definitive disruption of the potential autoreactive clone(s). This is in line with the evidence that in IMN, persistent remission achieved by rituximab therapy is paralleled by depletion of nephritogenic autoantibodies, even after re-emergence of B lymphocytes in the circulation.…”

“…With the exception of few reports in steroid-dependent MCD, [11][12][13]26 most previous studies tested the standard four weekly 375 mg/m 2 dose regimen originally implemented for the treatment of relapsing or refractory non-Hodgkin's lymphoma, 15 a regimen, in several cases, that was followed by additional doses infused in the attempt to achieve some degree of remission after initial treatment failure. However, we reasoned that dysfunctional B-cell mass here is remarkably lower than in B-cell malignancies and that lower doses of rituximab would fully deplete aberrant B-cell clones, as previously observed in 36 IMN patients with long-lasting, persistent NS.…”

“…7 Subsequent uncontrolled observations found some effect of rituximab in patients with steroid-dependent or frequently relapsing MCD, [8][9][10][11] suggesting that B-cell immunity could play a key role in the pathophysiology of the disease. Controlled studies in support of this hypothesis, however, have been both scanty and almost confined to children 12,13 or to patients with MCD who were evaluated in the context of a retrospective, observational design. 14 Indeed, less attention was given to adults and patients with FSGS given difficulties in designing adequately powered trials.…”

Anti-CD20 Antibodies for Idiopathic Nephrotic Syndrome in Children

“…Successive retrospective studies reported between 2008 and 2011 (17)(18)(19)(20)(21)(22)(23)(24)(25)(26) confirmed these potential benefits in uncontrolled small series of mixed populations with nephrotic syndrome. Although these studies could not assist in decision making because of their observational design, they were key to informing the design of subsequent clinical trials that have been completed in the last 5 years.…”

Remission Induction Therapy with Rituximab for Microscopic Polyangiitis: A Feasibility Study

“…Studies have shown that a single dose of RTX is effective in the treatment of some types of nephrotic syndromes including minimal change of nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) (Kamei et al 2009;Ochi et al 2012). These reports suggest that relapses develop simultaneously with the recovery of B-cells.…”