NEWS & VIEWS NEPHROTIC SYNDROME
Efficacy of rituximab in challenging nephrotic syndrome Kevin V. Lemley and Robert H. Mak Refers to Ravani, P. et al. Rituximab in children with steroid-dependent nephrotic syndrome: a multicentre, open-label, noninferiority, randomized controlled trial. J. Am. Soc. Nephrol. http://dx.doi.org/10.1681/ASN.2014080799
A new trial provides further evidence that rituximab treatment can reduce the risk of relapse in children with steroid-dependent idiopathic nephrotic syndrome. Addition of a single infusion of rituximab to steroid therapy was associated with a decrease in proteinuria at 3 months and a significant increase in the relapse-free period. The treatment of patients with steroiddependent nephrotic syndrome remains a vexing challenge for nephrologists. Patients with steroid toxicity are often treated with steroid-sparing agents, such as ciclosporin or cyclophosphamide, but these also have toxic effects.1 Over the past decade, newer agents for treating nephrotic syndrome—principally mycophenolate and rituximab—have been added to the armamentarium of nephrologists but these have not been widely validated or adopted. Now, Ravani and colleagues present new data from a well-designed, multicentre, randomized, non-blinded, noninferiority trial of intravenous rituximab versus continued steroid therapy in 30 children with steroid- dependent idiopathic nephrotic syndrome of fairly short duration (6–12 months).2 At the time of enrolment the participants were being maintained in remission with use of high-dose prednisone (≥0.7 mg/kg daily) without calcineurin inhibitors.
‘‘
…66% of patients in the rituximab group were relapse-free at 1 year versus none … in the control group
’’
After a 1 month run-in period, during which steroid doses were minimized, half of the patients received a single intravenous dose of rituximab (375 mg/m2). All parti cipants then continued with oral prednisone treatment for 1 month before a steroid taper was attempted following a defined protocol (0.3 mg/kg per week). In the control group,
relapse (defined as proteinuria >1 g/m 2 per day) was treated with prednisone or steroid-sparing agents at the discretion of local physicians. In the rituximab group, relapse was treated with an additional dose of rituximab. All participants were monitored for relapse for at least 1 year (median 22 months). In addition, white blood cell counts and lymphoc yte subsets were assessed monthly in the r ituximab group.2 At 3–month follow-up, quantitative proteinuria had decreased from baseline in the rituximab group and increased in the control group, resulting in a nonsignificant between-group difference of 42%, despite higher doses of prednisone in the latter group (0.54 ± 0.39 mg/kg per day versus 0.09 ± 0.21 mg/kg per day, P 12 months,3 they likely had a more severe and persistent form of disease than those included in the recent trial.2 A similar study of 48 paediatric patients with complicated frequently relapsing or steroid-dependent nephrotic syndrome reported favourable results with four weekly infusions of rituximab.4 In this placebocontrolled trial, treatment with rituximab immediately after oral steroid treatment for relapse resulted in an increase in the median relapse-free period from 101 to 267 days (hazard ratio 0.27, P
Efficacy of rituximab in challenging nephrotic syndrome Kevin V. Lemley and Robert H. Mak Refers to Ravani, P. et al. Rituximab in children with steroid-dependent nephrotic syndrome: a multicentre, open-label, noninferiority, randomized controlled trial. J. Am. Soc. Nephrol. http://dx.doi.org/10.1681/ASN.2014080799
A new trial provides further evidence that rituximab treatment can reduce the risk of relapse in children with steroid-dependent idiopathic nephrotic syndrome. Addition of a single infusion of rituximab to steroid therapy was associated with a decrease in proteinuria at 3 months and a significant increase in the relapse-free period. The treatment of patients with steroiddependent nephrotic syndrome remains a vexing challenge for nephrologists. Patients with steroid toxicity are often treated with steroid-sparing agents, such as ciclosporin or cyclophosphamide, but these also have toxic effects.1 Over the past decade, newer agents for treating nephrotic syndrome—principally mycophenolate and rituximab—have been added to the armamentarium of nephrologists but these have not been widely validated or adopted. Now, Ravani and colleagues present new data from a well-designed, multicentre, randomized, non-blinded, noninferiority trial of intravenous rituximab versus continued steroid therapy in 30 children with steroid- dependent idiopathic nephrotic syndrome of fairly short duration (6–12 months).2 At the time of enrolment the participants were being maintained in remission with use of high-dose prednisone (≥0.7 mg/kg daily) without calcineurin inhibitors.
‘‘
…66% of patients in the rituximab group were relapse-free at 1 year versus none … in the control group
’’
After a 1 month run-in period, during which steroid doses were minimized, half of the patients received a single intravenous dose of rituximab (375 mg/m2). All parti cipants then continued with oral prednisone treatment for 1 month before a steroid taper was attempted following a defined protocol (0.3 mg/kg per week). In the control group,
relapse (defined as proteinuria >1 g/m 2 per day) was treated with prednisone or steroid-sparing agents at the discretion of local physicians. In the rituximab group, relapse was treated with an additional dose of rituximab. All participants were monitored for relapse for at least 1 year (median 22 months). In addition, white blood cell counts and lymphoc yte subsets were assessed monthly in the r ituximab group.2 At 3–month follow-up, quantitative proteinuria had decreased from baseline in the rituximab group and increased in the control group, resulting in a nonsignificant between-group difference of 42%, despite higher doses of prednisone in the latter group (0.54 ± 0.39 mg/kg per day versus 0.09 ± 0.21 mg/kg per day, P 12 months,3 they likely had a more severe and persistent form of disease than those included in the recent trial.2 A similar study of 48 paediatric patients with complicated frequently relapsing or steroid-dependent nephrotic syndrome reported favourable results with four weekly infusions of rituximab.4 In this placebocontrolled trial, treatment with rituximab immediately after oral steroid treatment for relapse resulted in an increase in the median relapse-free period from 101 to 267 days (hazard ratio 0.27, P
