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. 2022 Feb;37(2):357-365.
doi: 10.1007/s00467-021-05069-w. Epub 2021 Jun 16.

Anti-rituximab antibodies in pediatric steroid-dependent nephrotic syndrome

Quentin Bertrand  1 , Sabine Mignot  2 , Theresa Kwon  3 , Anne Couderc  3 , Anne Maisin  3 , Alexandra Cambier  3 , Véronique Baudouin  3 , Marine Peyneau  2 , Georges Deschênes  3 , Julien Hogan  3 , Claire Dossier  3
Affiliations

Anti-rituximab antibodies in pediatric steroid-dependent nephrotic syndrome

Quentin Bertrand et al. Pediatr Nephrol. 2022 Feb.

Abstract

Background: Rituximab is a chimeric anti-CD20 monoclonal antibody that induces sustained remission in children with steroid-dependent nephrotic syndrome. However, there is no consensus on the optimal regimen and monitoring of rituximab. In other autoimmune diseases, anti-rituximab antibodies (ARA) have been reported in 10-40% of patients, but their clinical relevance remains unclear. In nephrotic syndrome, data are scarce.

Methods: We report a single-center retrospective study with immuno- and pharmacological monitoring of rituximab treatment in children with frequent relapsing (FR) or steroid-dependent nephrotic syndrome (SDNS). We analyzed the monthly monitoring of 24 children, receiving a dose of rituximab (375 mg/m2) between December 2017 and April 2018 at the Pediatric Nephrology Department of Robert-Debré hospital, Paris.

Results: ARA were detected in 7/24 patients (29%), sometimes after the first infusion of rituximab. ARA were present at baseline in two patients previously treated with rituximab. Both displayed no B-cell depletion. ARA were also reported in 5/22 patients during follow-up, with antibodies always detected in the first month following B-cell recovery. An incomplete CD19+CD20- B-cell depletion at M1 (5-25/mm3) and low serum rituximab levels was predictive of developing ARA. The development of de novo ARA during follow-up was not associated with shorter B-cell depletion.

Conclusions: This study shows that ARA are frequent in children with FR/SDNS and that close immuno- and pharmacological monitoring may help personalizing rituximab treatment in patients needing repeated injections.

Keywords: Anti-rituximab antibodies; Children; Rituximab; Serum rituximab levels; Steroid-dependent nephrotic syndrome.

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