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Abstract: TH-PO588

Randomized Controlled Trial Comparing Rituximab to Mycophenolate Mofetil in Children and Young Adults with Steroid-Dependent Idiopathic Nephrotic Syndrome

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Angeletti, Andrea, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Caridi, Gianluca, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Lugani, Francesca, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Vivarelli, Marina, Ospedale Pediatrico Bambino Gesu, Roma, Italy
  • Emma, Francesco, Ospedale Pediatrico Bambino Gesu, Roma, Italy
  • Ghiggeri, Gian Marco, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Colucci, Manuela, Ospedale Pediatrico Bambino Gesu, Roma, Italy
  • Gargiulo, Antonio, Ospedale Pediatrico Bambino Gesu, Roma, Italy
  • Cravedi, Paolo, Icahn School of Medicine at Mount Sinai, New York, New York, United States
Background

Steroids induce remission in 90% of children with idiopathic nephrotic syndrome (INS). Some become steroid-dependent (SD) and require the addition of drugs such as calcineurin-inhibitors (CNI), to maintain remission. Considering the toxicity of these drugs, alternative interventions are needed. The anti-CD20 antibody rituximab was effective as a steroid-sparing agent. Mycophenolate mofetil (MMF) is effective in maintaining free-steroid remission, however, studies are limited to a few uncontrolled trials with different doses of MMF.

Methods

This open-label, two-parallel-arm, multi-center, superiority-controlled randomized clinical trial will enroll children with SD-INS maintained in remission with oral glucocorticoids or CNI. Subjects will be randomized to either MMF (1.200 mg/m2) or rituximab (375 mg/m2) infusion. Glucocorticoids will be 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).

Conclusion

A single dose of rituximab was superior to a single MMF in maintaining remission in children with steroid-dependent and CNI–dependent nephrotic syndrome.