059 Pharmacodynamics of rituximab on B cells in paediatric patients with immune disorders

Abstract

Background Rituximab is a chimeric IgG-1 monoclonal antibody that depletes B cells, aiding in the treatment of several conditions including autoimmune and immunodeficiency diseases. It is not licensed for use in children but administered off-label. The current study aimed to identify the pharmacodynamics of rituximab in children with immune disorders in order to optimise the dosing regimen. Methods Electronic data of children prescribed with rituximab at Great Ormond Street Hospital, London, United Kingdom were collected from a retrospective and anonymised study. Two intravenous infusions of rituximab, each at a dose of 750 mg/m2 with a maximum dose of 1000 mg, were given at day 1 and 15 within 6 months. Plasma concentrations of rituximab were not available. CD19 +B cell counts were measured before and after rituximab treatment. A turnover model was constructed in NONMEM (version 7.3) to describe the life cycle of CD19 +B cells considering the effect of rituximab on increasing the death rate of CD19 +B cells. Rituximab was assumed to be eliminated by first-order kinetics. Results 296 measurements of CD19 +B cell counts were collected from 46 children with 13 different immune diseases. The 2-compartment model well described the time course of CD19 +B cells following rituximab administration. The elimination half-life of rituximab and CD19 +B cells were estimated to be 18 and 40 days, respectively; these findings were consistent with that reported from the literature. ?Methotrexate and cyclophosphamide were found to increase the killing effect by 62% and 33%, respectively. Other covariates such as age and gender were not found significant. Conclusions The findings from the current study will be used to establish dosing regimens of rituximab for treating children with immune diseases.