Investigators from multiple Japanese institutions conducted a retrospective observational study to assess the long-term clinical course among children with frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS) treated after treatment with rituximab. Patients with childhood-onset FRNS or SDNS, who had received 375 mg/m2 rituximab once weekly for 4 weeks as part of a clinical trial conducted from 2008–2010, were eligible to participate. FRNS was defined as ≥4 relapses of nephrotic syndrome within any 12-month period. SDNS was defined as 2 consecutive relapses during tapering or within 2 weeks of discontinuation of steroid treatment.
Patients were followed clinically until 2014. Patients were assessed for disease relapse, need for additional rituximab treatment, immunosuppressive agent treatment, renal function, and rituximab-related adverse events. Demographics and age of onset of disease were also collected. Investigators used Kaplan-Meier survival curves to determine relapse-free remission time (measured in days) after rituximab treatment.
There were 51 patients included in analysis. Most patients were male (75%) and had a median age of 11 years. Median age at onset of FRNS or SDNS was 3 years. Overall, 94% of patients (N=48) developed relapses during the study period, with a median relapse-free remission time of 261 days. Among those who relapsed, 86% underwent re-administration or continuation of immunosuppressive agents, and 43% received additional rituximab treatment. Among 13 patients who did not require immunosuppressive agents at the time of initial rituximab treatment, 5 did not require further rituximab or immunosuppressive agents and 3 did not relapse during the study period. No patients developed chronic renal insufficiency, and there were no rituximab-related adverse events.
The investigators conclude that most patients with FRNS and SDNS treated with rituximab suffer relapse and require additional rituximab treatment or long-term immunosuppressive agents.
Dr Singer has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.
The development of alternatives to corticosteroids for the management of nephrotic syndrome remains an area of great interest for pediatric nephrologists. In a study recently reviewed in AAP Grand Rounds, the use of lower steroid dosing was evaluated (AAP Grand Rounds, April 2017;37:391 ). Other researchers have examined the use of second-line immunosuppressive agents. While oral agents such as tacrolimus and mycophenolate are frequently used, these long-term, twice-daily medications pose problems for patient compliance and tolerability. As an IV agent, rituximab is a promising alternative. In an earlier study conducted by the investigators in the present study, use of rituximab was found to be superior to placebo in patients with FRNS and SDNS, with longer time to relapse (median of 267 days) and lower rate of steroid use post-treatment.2
The current study included both patients who...