BackgroundRituximab is a chimeric IgG1 monoclonal antibody that depletes B cells for the treatment of several conditions including autoimmune diseases. It is not licensed for use in children but administered off-label. This study aimed to quantify the effect of rituximab on B cell depletion in children with autoimmune diseases and to optimise the dosing regimen.MethodsElectronic health record data were collected from a retrospective and anonymised study at Great Ormond Street Hospital in London. Dosing protocols of rituximab were two 750 mg/m2 intravenous infusions or four weekly 375 mg/m2 infusions. Serum concentrations of rituximab were not measured. CD19+ lymphocyte counts were taken before and after rituximab treatment. A turnover mechanism described the life cycle of CD19+ lymphocytes with rituximab increasing the death rate of CD19+ lymphocytes; a negative feedback was added on the production rate to examine the rebound effect. Rituximab was assumed to decay by first-order kinetics.Results258 measurements of CD19+ lymphocyte counts were collected from 39 children with 8 autoimmune diseases. The dose-response model well described the time course of CD19+ lymphocytes following rituximab administration. The elimination half-lives of rituximab and CD19+ lymphocytes were estimated to be 19 and 35 days, respectively, consistent with findings from other studies [1–5]. The rebound increase in CD19+ lymphocytes was found negligible. Methotrexate and cyclophosphamide increased the maximum death rate by 66% and 38% respectively. Age and gender were not significant covariates.Simulations from the model suggested that a single infusion of rituximab of 375 mg/m2 can provide similar six-month suppression of CD19+ lymphocytes to the higher doses currently used. Methotrexate or cyclophosphamide added minimal suppression effect on CD19+ lymphocytes when taken concurrently with rituximab.ConclusionsOur results could be used in future to assess the effect of rituximab biosimilars and to inform biosimilar dosing in paediatric populations.ReferencesNg, et al. J Clin Pharmacol. 2005; 45:792–801Li, et al. Blood. 2007; 110:2371Li, et al. J Clin Pharmacol. 2012; 52:1918–26Fulcher and Basten. Immunol Cell Biol. 1997; 75:446–55Macallan, et al. Blood. 2005; 105:3633–40Disclosure(s)Nothing to disclose
CD20+ B Cell Depletion in Systemic Autoimmune Diseases: Common Mechanism of Inhibition or Disease-Specific Effect on Humoral Immunity?