Intravenous tocilizumab is currently dosed on body weight, although a weak correlation between body weight and clearance has been described. The aim of the study was to assess the current dosing strategy and provide a scientific rational for dosing using a modelling and simulation approach.
Serum concentrations and covariates were obtained from intravenous tocilizumab treated subjects at a dose of 4, 6 or 8 mg every 28 days. A population pharmacokinetic analysis was performed using nonlinear mixed effects modelling. The final model was used to simulate tocilizumab exposure to assess a dosing strategy based on body weight or fixed dosing, using as target a cumulative area under the curve at 24 weeks of treatment above 100 × 10
A one-compartment disposition model with parallel linear and nonlinear elimination best described the concentration-time data. The typical population mean values for clearance, apparent volume of distribution, maximum elimination rate and Michaelis-Menten constant were 0.0104 l h
Our study provides evidence to support fixed dosing of intravenous tocilizumab in rheumatoid arthritis patients since it reduces variability in tocilizumab exposure among weight categories compared to the current weight-based dosing approach.