Rituximab for very low dose steroid-dependent nephrotic syndrome in children: a randomized controlled study.

Abstract

Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, randomized controlled trial was designed to test whether the monoclonal antibody rituximab is non-inferior to steroids in maintaining remission in juvenile forms of SDNS and how long remission may last (EudraCT:2008-004486-26). We enrolled 30 children 4-15years who had developed SDNS 6-12months before and were maintained in remission with low prednisone doses (0.1-0.4mg/Kg/day). Participants were randomized following a non-inferiority design to continue prednisone alone (n 15, controls) or to add a single intravenous infusion of rituximab (375mg/m2, n 15 intervention). Prednisone was tapered in both arms after 1month. Children assigned to the control arm were allowed to receive rituximab to treat disease relapse. Proteinuria increased at 3months in the prednisone group (from 0.14 to 1.5g/day) (p < 0.001) and remained unchanged in the rituximab group (0.14g/day). Fourteen children in the control arm relapsed within 6months. Thirteen children assigned to rituximab (87%) were still in remission at 1year and 8 (53%) at 4years. Responses were similar in children of the control group who received rituximab to treat disease relapse. We did not record significant adverse events. Rituximab was non-inferior to steroids for the treatment of juvenile SDNS. One in two children remains in remission at 4years following a single infusion of rituximab, without significant adverse events. Further studies are needed to clarify the superiority of rituximab over low-dose corticosteroid as a treatment of SDNS.