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, 212% [95% confidence interval, 273% 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.

Rituximab in Steroid-Dependent or Frequently Relapsing Idiopathic Nephrotic Syndrome

“…22 These findings extend previous evidence that rituximab reduced proteinuria and the need for immunosuppressive therapy at 3-month follow-up in 54 children with steroiddependent idiopathic NS 12 and limited the risk of relapses in 17 adults with steroid-dependent MCD, 10 whereas it failed to appreciably affect disease outcome in children with resistant idiopathic NS. 23 The finding that the treatment effect was sustained over 2 years of follow-up was consistent with recent evidence that prolonged remission could be achieved with 1-5 courses of rituximab in a substantial proportion of children with previous steroid-dependent or calcineurin inhibitordependent NS. 24 On the other hand, the finding that patients with FSGS had the same response to treatment compared with those with MCD or MesGN was particularly intriguing.…”

Ofatumumab for Rituximab-Resistant Nephrotic Syndrome

“…1 Here, we describe an unexpectedly high number of cases of thrombotic microangiopathy associated with severe or malignant hypertension in four patients with multiple sclerosis who were receiving therapy with recombinant interferon beta in South Scotland. A detailed review of the case histories of these patients, including a genetic analysis, did not identify any other causal factor for this condition, and an analysis of pharmacy records revealed a significant association with a common manufacturing source of interferon beta (Rebif, Merck) (Fig.…”

Rituximab-based novel strategies for the treatment of immune-mediated glomerular diseases

“…Importantly, 63% of patients treated with RTX were drug-free at 3 months versus 3.7% in the control arm. A more recent, open-label, randomized controlled trial on the use of RTX in children with steroid-resistant nephrotic syndrome failed to demonstrate that adding RTX to prednisone and calcineurin inhibitors was effective in these patients [86]. One problem with this study is that it may not have had enough power given its small sample size of 31 patients, and it only had 3 months of follow-up at the time of publication.…”