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P339 Application of Bayesian modelling with infliximab to determine optimal patient-specific regimens

T. E. Ritter*1, H. E. SarlesJr2, R. C. McLeay3, L. J. Van Anglen4, C. P. Schroeder4, T. C. Hardin4

1Texas Digestive Disease Consultants, PA, Clinical Research and Education, Southlake, TX, USA, 2Digestive Health Associates of Texas, PA, DHAT Research Institute, Richardson, TX, USA, 3DoseMe, Brisbane, Qld, Australia, 4Healix, Pharmacy and Clinical Research, Sugar Land, TX, USA

Background

Infliximab (IFX), a chimeric monoclonal IgG1 anti-TNF-α antibody, is often used to treat inflammatory bowel disease (IBD), particularly if non-biologic treatments have failed. IFX is usually administered intravenously at the approved standard dose of 5 mg/kg initially at Weeks 0, 2, and 6, then in standard dose intervals of every 8 weeks. Individualisation of IFX dosing to optimise clinical response is considered desirable with an accepted target trough serum concentration of ≥5 µg/ml, yet application of therapeutic drug monitoring (TDM) is often difficult due to significant patient variability. To assist clinicians with individualised IFX dosing, a Bayesian pharmacokinetic dosing strategy was developed.

Methods

The electronic medical records of adult IBD patients treated with IFX at gastroenterology physician office infusion centres were retrospectively reviewed. All patients receiving IFX with a minimum of two serum concentration measurements and 3 infliximab doses prior to serum levels were identified. Data collected from these records included patient demographics, pertinent laboratory, IFX dosing history, serum IFX concentrations, timing of TDM relative to dosing, type of IFX assay employed, and presence of IFX antibodies. The predictive performances of a previously published model (Ternant et al.) were evaluated on this external patient cohort. Further protocol assessment and clinical validation of this dosing tool are currently underway.

Results

We identified 87 patients who met our inclusion criteria. The mean age was 42 (range 18–76), mean weight was 79.5 kg (range 47–141.5), and 47% male. 174 serum samples were assayed, with each patient assigned to one of the two commercially available assay types. A robust Bayesian pharmacokinetic dosing platform was implemented satisfactorily, providing accurate individual concentration predictions (bias −0.28 mg/l; RMSE 4.7); however, the bias and precision of forecasted trough concentrations varied significantly based on assay method.

Conclusion

We developed a unique decision support dosing tool for use with IFX. This platform provides clinical guidance for IFX dosing based on patient characteristics and pharmacokinetic principles and supports individualisation of both IFX dose and interval.