Rituximab-induced long-term remission in childhood-onset, uncomplicated, frequently relapsing or steroid-dependent nephrotic syndrome: a randomized, placebo-controlled trial and a follow-up study.

Rituximab maintains remission of complicated frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS) by depleting peripheral B cells, but most patients eventually experience relapses after B cell recovery. We performed a multicenter, double-blind, randomized, placebo-controlled trial to assess rituximab's efficacy and safety for childhood-onset uncomplicated FRNS/SDNS (without prior treatment with glucocorticoid-sparing immunosuppressive agents) with a follow-up study to assess rituximab's long-term effect after B cell recovery. Patients were randomly assigned to receive either rituximab (375 mg/m², maximum 500 mg, once weekly for 2 weeks) or placebo. The primary endpoint was the relapse-free period. Of 43 randomized patients, 40 received the intervention (18 rituximab, 22 placebo). The relapse-free period during the 1-year trial was significantly longer in the rituximab vs. placebo groups (median: 285 vs. 81 days; p < 0.001). Infusion reactions were more frequent in the rituximab group (p < 0.001), with no difference in adverse events incidence between the groups. Interestingly, the follow-up study demonstrated markedly higher 3-year cumulative relapse-free survival probability without further treatments in the rituximab vs. placebo groups (38% vs. 9%). A mini-systematic review with meta-analyses supported the findings. Rituximab is effective and well-tolerated, potentially leading to long-term remission with substantially high rates after B cell recovery for childhood-onset uncomplicated FRNS/SDNS.Trial registration JSKDC10, Clinical Trials Registry ID: jRCT1091220380; JSKDC10 follow-up study, Clinical Trials Registry ID: jRCT1050230024.