Rituximab in children with steroid-dependent nephrotic syndrome: A multicenter, open-label, noninferiority, randomized controlled trial

Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity fromsteroids or steroid-sparing agents. This open-label,noninferiority,randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1-16 years who had developed SDNS in the previous 6-12 months and weremaintained in remission with high prednisone doses (≥0.7mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m2; intervention). Prednisone was tapered in both groups after 1month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m2 per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome).We followed participants for ≥1 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6-13.5 years]) were enrolled and followed for ≤60 months (median, 22months). Three-month proteinuria was 42%lower in the rituximab group (geometricmean ratio, 0.58; 95%confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6months; median timeto relapse in the rituximab group was 18months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS.