Rituximab May Treat Early-Onset Nephrotic Syndrome

In children, idiopathic nephrotic syndrome (NS) generally responds well to treatment with corticosteroids, but long-term use of steroids in children can produce adverse effects (AEs) such as growth impairment and hypertension. Calcineurin inhibitors, too, are associated with AEs, including toxicity and diabetes. Rituximab has been proposed as an option for difficult-to-treat childhood-onset NS, and a recent study evaluated the efficacy and safety of a single dose of rituximab in this setting.

The study, a multicenter, open-label trial conducted in Korean patients with childhood-onset NS, involved patients aged under 24 years who were either drug-dependent for more than 2 years or who were intolerant to standard treatment.

The study’s design involved a randomized controlled trial (RCT) for drug-dependent patients and a single-arm study for patients whose disease was resistant to conventional treatment. In the RCT, patients were randomly assigned to receive either rituximab (n = 40) or standard treatment (n = 21), and in the single-arm study, all patients (n = 23) received rituximab in addition to their pre-enrollment treatment.

The primary end points of the study were the rate of retaining remission at 6 months in the RCT and the rate of remission within 6 months of starting rituximab in the single-arm study.

In the RCT, at 6 months, 74.3% of rituximab-treated patients were at remission, while 68.7% of standard therapy patients in the control group were in relapse (P = .003). The median duration of remission in the rituximab group was 9 months versus 2.9 months in the standard therapy group.

In the single-arm study, within 6 months of starting rituximab, 9 patients achieved either partial (n = 2) or complete (n = 7) remission.

In all patients treated with rituximab, CD19-positive B cells were depleted within 2 weeks of rituximab treatment. However, relapse after rituximab was not always linked with B-cell recovery; 4 patients had depleted B cells at the time of NS relapse.

In total, 50.8% of patients had infusion reactions to rituximab, and 5 of these patients discontinued infusion (all 5 patients were able to tolerate subsequent rituximab administrations, however). A total of 21 patients reported infections, and 45 experienced any AE. One patient died during the study, but the death was not attributable to rituximab therapy, the investigators concluded.

“Our study laid one more piece of evidence that [rituximab] can be safe and effective in patients with childhood-onset, medication-dependent NS,” wrote the authors, adding that controlled studies are warranted to determine the optimal dosing and interval for rituximab administration in patients with hard-to-treat NS.

Reference

Anh YH, Kim SH, Han KH, et al. Efficacy and safety of rituximab in childhood-onset, difficult-to-treat nephrotic syndrome: a multicenter open-label trial in Korea. Medicine (Baltimore). 2018;97:e13158. doi: 10.1097/MD.0000000000013157.