Long-Term Efficacy and Safety of Rituximab Versus Tacrolimus in Children With Steroid Dependent Nephrotic Syndrome

Abstract

In the Rituximab for Relapse Prevention in Nephrotic Syndrome (RITURNS) trial, we demonstrated superior efficacy of single-course rituximab over maintenance tacrolimus in preventing relapses in children with steroid dependent nephrotic syndrome (SDNS) during a 1-year observation. Here we present the long-term outcomes of all 117 trial completers, who were followed up for another 2 years. Relapsing patients in the rituximab arm received a second course of rituximab, either with (n= 44) or without mycophenolate mofetil (MMF) cotreatment (n= 15). In the tacrolimus arm, second line rituximab monotherapy was initiated after relapses (n= 32) or electively (n= 24). All 12-month relapse-free patients in the rituximab arm relapsed in the second postexposure year, resulting in similar median relapse-free survival times in the 2 trial arms (62 vs. 59 weeks). Second line rituximab in the tacrolimus arm was less effective than first-line therapy in patients switched to rituximab following a relapse (relapse-free survival 55 vs. 63 weeks, P< 0.01). B-cell counts 6 months post-rituximab predicted relapse risk both for first and second line therapy. MMF cotreatment yielded much improved 2-year relapse-free survival as compared to rituximab monotherapy (67% vs. 9%, P< 0.0001). Higher grade 2 adverse event rates were observed post-rituximab versus on tacrolimus (0.87 vs. 0.53 per year). The superior therapeutic effect of rituximab in SDNS vanishes during the second year post-exposure. Rituximab appears to yield longer remission when applied as first line as compared to second line therapy. Maintenance MMF following rituximab induces long-term disease remission.