Safety of Obinutuzumab in Children With Autoimmune Encephalitis and Early B-Cell Repopulation on Rituximab

Ai-Tien Nguyen; Camille Cotteret; Clarisse Gins; Eugénie Sarda; Chloé Durrleman; Bettina Mesples; Jacinta Bustamante; Claire Fayard; Salvatore Cisternino; Isabelle Desguerre; Mélodie Aubart

doi:10.1016/j.pediatrneurol.2024.04.013

Safety of Obinutuzumab in Children With Autoimmune Encephalitis and Early B-Cell Repopulation on Rituximab

Pediatr Neurol. 2024 Apr 18:156:79-84. doi: 10.1016/j.pediatrneurol.2024.04.013. Online ahead of print.

Affiliations

¹ Department of Pediatric Neurology, Necker-Enfants Malades Hospital, University of Paris Cité, AP-HP, Paris, France.
² Department of Clinical Pharmacy, Necker-Enfants Malades Hospital, University of Paris Cité, AP-HP, Paris, France.
³ Department of Pediatrics, Louis Mourier Hospital, University of Paris Cité, AP-HP, Paris, France.
⁴ Study Center for Primary Immunodeficiencies, Necker-Enfants Malades Hospital, University of Paris Cité, AP-HP, Paris, France; Faculty of Pharmacy, Team Blood-Brain Barrier in Brain Pathophysiology and Therapy, University of Paris Cité, INSERM UMRS 1144, Paris, France.
⁵ Department of Clinical Pharmacy, Necker-Enfants Malades Hospital, University of Paris Cité, AP-HP, Paris, France; Faculty of Pharmacy, Team Blood-Brain Barrier in Brain Pathophysiology and Therapy, University of Paris Cité, INSERM UMRS 1144, Paris, France.
⁶ Department of Pediatric Neurology, Necker-Enfants Malades Hospital, University of Paris Cité, AP-HP, Paris, France; Human Genetics of Infectious Diseases, INSERM UMR 1163, University of Paris Cité, Institut Imagine, Paris, France. Electronic address: melodie.aubart@aphp.fr.

PMID: 38733858
DOI: 10.1016/j.pediatrneurol.2024.04.013

Abstract

Background: Rituximab (RTX) resistance or early B-cells repopulation were observed in children but only few publications reported the use of Obinutuzumab and no recommendations were made concerning the dosage for children.

Methods: This study was a single-center retrospective cohort study of all the children followed-up in the Pediatric Neurology Department of Necker-Enfants malades Hospital in Paris, France, and treated with obinutuzumab, between November 1, 2019, and November 1, 2021.

Results: A total of eight children (three females, median age 4.5 years) were treated. Seven patients presented with autoimmune encephalitis and one with myeloradiculitis. The median delay of B-cell repopulation after a course of RTX was 87 days (range 41 to 160). A switch to obinutuzumab (anti-CD20) was performed for eight children. The median duration between the first RTX infusion and obinutuzumab administration was 6.6 months. The dosage regimen for obinutuzumab was one infusion of 1000 mg/1.73 m², that is to say 580 mg/m² (maximum 1000 mg/infusion), by extrapolation from the adult dosage. The median delay of B-cell repopulation after one course of obinutuzumab was 230 days (range 66 to 303 days) vs 87 days after one course of RTX (P < 0.01). None of the patients presented side effects with obinutuzumab treatment. All patients had a favorable evolution at the last-follow up. Median follow-up was 1.6 years.

Conclusions: This study reports the use of obinutuzumab in neurological inflammatory diseases in a pediatric population. Obinutuzumab seems to have a better biological efficacy than RTX with a longer time of B-cell repopulation.

Keywords: B lymphocytes; Neurology; Obinutuzumab; Pediatrics; Rituximab.