RANDOMISED CONTROLLED TRIAL COMPARING RITUXIMAB TO MYCOPHENOLATE MOFETIL IN CHILDREN AND YOUNG ADULTS WITH STEROID-DEPENDENT IDIOPATHIC NEPHROTIC SYNDROME

Introduction:

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.

Methods:

This is an open-label, two-parallel-arm, multi-center, superiority-controlled randomized clinical trial in SD-INS maintained in remission with oral glucocorticoids or CNI. Subjects were randomized to either MMF (1.200 mg/m2) or rituximab (375 mg/m2) infusion. 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 1-year relapse. In a sub-cohort of 39 patients (rituximab, n=19; MMF, n=20), we characterized the circulating levels of the B-cell subsets by flow cytometry.

Results:

We randomized 160 children and young adults (aged 2–24 years) (Fig1A). At 1 year, 12 of 80 (15%) participants who received rituximab experienced relapse versus 30 of 80 (37%) who received rituximab (odds ratio [OR], 2.27; 95% confidence interval [95% CI], 1.20 to 4.29) (Fig1B). As expected, there were no significant differences in B-cell subsets between the two arms at baseline. MMF treatment had no significant effect on B cells, while RTX depleted all B-cell subsets. By 1yr, total, transitional and mature-naïve B cells were restored to levels similar to the MMF arm (Fig.1A-B-C).

Conclusions:

A single dose of rituximab was superior to MMF in maintaining remission at 1yr of follow-up in children with steroid-dependent and CNI–dependent nephrotic syndrome.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.