#3335 Randomised controlled trial comparing rituximab to mycophenolate mofetil in children and young adults with steroid-dependent idiopathic nephrotic syndrome

Abstract Background and Aims Steroids induce remission in 90% of children with idiopathic nephrotic syndrome (INS). Some patients become steroid-dependent (SD) and require additional drugs like calcineurin inhibitors (CNI) to maintain remission. Due to the toxicity of these drugs, alternative interventions are needed. The anti-CD20 antibody rituximab has been effective as a steroid-sparing agent. Mycophenolate mofetil (MMF) is also effective in maintaining steroid-free remission, but studies are limited to a few uncontrolled trials with varying MMF doses. Method This is an open-label, two-parallel-arm, multi-center, superiority-controlled randomized clinical trial in SD-INS maintained in remission with oral glucocorticoids. Subjects were be randomized to either MMF (1.200 mg/m2) or single rituximab infusion (375 mg/m2). Glucocorticoids were tapered until complete withdrawal. The primary end-point is to detect as significant at the two-sided p-value of 0.01 with a power >0.8 a reduction in the risk of 2-years relapse. Results We randomized 160 children and young adults (aged 2–24 years) and we enrolled 156 subjects (Fig. 1A). At 2 years, 30 of 78 (37%) participants who received rituximab experienced relapse versus 22 of 78 (26%) who received MMF (odds ratio [OR], 1.45; 95% confidence interval [95% CI], 0.8 to 2.7) (Fig. 1B). No major adverse events ere reported. In a subset of patients (n = 56) we compared. The median age of the entire cohort was 9 years. Therefore, we defined the risk of 2-years relapse based on age at randomization. In >9 years cohort, 34% who received rituximab experienced relapse versus 28% who received MMF. In <9 years cohort, 41% who received rituximab experienced relapse versus 22% who received MMF (Fig. 1C and D). Conclusion A single dose of rituximab was not superior to MMF in maintaining remission at 2 years of follow-up in children and young adults with steroid-dependent nephrotic syndrome. Our findings also suggest that rituximab may be more effective in older subjects.