Rituximab for Treatment of Pediatric CNS Inflammatory Disorders

Jeffrey M. Gelfand, MD, MAS

A survey from an international network of pediatric centers highlights benefit and safety considerations of rituximab for neuroinflammatory indications.

Rituximab is a chimeric monoclonal CD20 antibody that results in B-cell depletion. To examine the off-label use of rituximab for numerous pediatric neuroinflammatory conditions, 15 pediatric centers collated standardized data of their clinical experience, focusing primarily on indication, safety, and disease outcome (functional status).

Of 144 children (103 female) treated with Rituximab for more than 13 different neuroimmunological indications, the four most common conditions treated were NMDAR encephalitis (27%), opsoclonus myoclonus ataxia syndrome (OMAS; 22%), neuromyelitis optica (NMO) spectrum disorders (14%), and neuropsychiatric systemic lupus erythematosus (NPSLE; 13%). Median age at rituximab administration was 9.9 years (range, 1.6–17.9 years); 46 (32%) of the children were aged 5 years or younger. Most (96%) of the children had been treated with one or more doses of glucocorticoids before commencing rituximab, 104 had previously received intravenous immunoglobulin, 43 had received cyclophosphamide, and 21 had undergone plasma exchange. A “definite” or “probable” benefit with rituximab, based on the impression of the treating clinician, was reported for 82% of children with NMDAR encephalitis, 75% with OMAS, and 65% with NMO. Two patients (one with multiple sclerosis and another with CNS vasculitis) had clinician-reported worsening of their disease. Administration of rituximab earlier in the disease course was associated with greater improvement in functional status (modified Rankin scale score) in NMDAR encephalitis, OMAS, NMO, and NPSLE.

Infusion-related anaphylaxis (grade 4 reaction) occurred in 2% of children and lower-grade reactions (most commonly rash) in another 10%. Infections or suspected infections were reported in 11 patients (7.6%).

Citation(s):

Dale RC et al. Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology 2014 Jun 11; [e-pub ahead of print].

Chitnis T and Waubant E.B-cell depletion in children with neuroimmunologic conditions: The learning curve. Neurology 2014 Jun 11; [e-pub ahead of print].