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Activity Number: 659 - Adaptive Dose Individualization
Type: Topic Contributed
Date/Time: Thursday, August 2, 2018 : 10:30 AM to 12:20 PM
Sponsor: Statistics and Pharmacometrics Interest Group
Abstract #328745 Presentation
Title: Bayesian Adaptive Dosing: Tailoring Patient Exposure Reduces Therapeutic Failures
Author(s): Diane Mould*
Companies: Projections Research, Inc.
Keywords: Individualized dosing; Bayesian adaptive dosing; monoclonal antibodies; inflammatory bowel disease; infliximab; therapeutic drug monitoring

Inflammatory bowel disease (IBD) patients failing chemical therapies need monoclonal antibodies (MAbs) but many show loss of response (LOR). MAbs have complex pharmacokinetics (PK). Many factors impact MAb PK: albumin weight disease (severity stage co-morbidities) glucose and immunosuppressants. Anti-drug antibodies (ADA) can affect PK and can occur quickly. Causes of LOR are low exposure inappropriate dosing high disease activity and ADA. Infliximab (IFX) discontinuation at 4 yrs is 46%. Post-hoc analyses suggested maintaining measurable IFX trough concentrations (TC) improves outcome. Therapeutic drug monitoring (TDM)-based dosing is cost-effective and may reduce LOR. Identifying effective doses using TDM is not intuitive or static owing to changing patient status and factors. A Bayesian dashboard system (DS) for MAbs for IBD was chosen due to need to quickly find appropriate doses. Retrospective studies showed faster identification of individualized dosage with DS with predicted LOR in advance of low TC. DS treatment recommendations were substantially different from standard of care but feasible. The DS is in clinical trials evaluating usefulness.

Authors who are presenting talks have a * after their name.

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