Rituximab in children with resistant idiopathic nephrotic syndrome

Abstract

Idiopathic nephrotic syndrome resistant to standard treatments remains a therapeutic dilemma in pediatric nephrology. To test whether the anti-CD20 monoclonal antibody rituximab may benefit these patients, we conducted an open-label, randomized, controlled trial in 31 children with idiopathic nephrotic syndrome unresponsive to the combination of calcineurin inhibitors and prednisone. All children continued prednisone and calcineurin inhibitors at the doses prescribed before enrollment, and one treatment group received two doses of rituximab (375 mg/m(2) intravenously) as add-on therapy. The mean age was 8 years (range, 2-16 years). Rituximab did not reduce proteinuria at 3 months (change, -12% [95% confidence interval, -73% to 110%]; P=0.77 in analysis of covariance model adjusted for baseline proteinuria). Additional adjustment for previous remission and interaction terms (treatment by baseline proteinuria and treatment by previous remission) did not change the results. In conclusion, these data do not support the addition of rituximab to prednisone and calcineurin inhibitors in children with resistant idiopathic nephrotic syndrome.

Figure 1.

Numbers of patients who were screened for the study, underwent randomization, and completed the study. CNI, calcineurin inhibitors; RTX, rituximab.

Figure 2.

Plots summarizing the distribution of proteinuria (g/d per m² [log-scale]), prednisone (mg/kg per day), and the proportion of children receiving full-dose calcineurin inhibitors (cyclosporine or tacrolimus) over time in months from randomization (time zero). Dark gray bars represent patients assigned to rituximab-based strategy; light gray bars represent standard therapy. The line across the box plots (proteinuria and prednisone plots) is the median, the box hinges are the 25th and 75th percentiles, and the outliers are represented as dots lying beyond 1.5 times the interquartile range. CNI, calcineurin inhibitors; PDN, prednisone; R, rituximab; S, standard therapy.