Pharmacokinetic Modeling and Simulation of Biologicals in Inflammatory Bowel Disease: The Dawning of a New Era for Personalized Treatment

Author(s): Erwin Dreesen, Ann Gils, Severine Vermeire*.

Journal Name: Current Drug Targets

Volume 19 , Issue 7 , 2018

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Abstract:

Background: Anti-tumor necrosis factor-alpha and anti-integrin monoclonal antibodies show great benefits for inducing and maintaining remission, healing the mucosa and restoring the quality of life of patients with inflammatory bowel disease. However, the therapeutic potential of these intrinsically powerful biologicals is abated by a high variability in response. Some patients experience no benefit from these treatments, while others lose response over time. Therapeutic Drug Monitoring (TDM) is a promising tool to further improve therapeutic outcome, substantiated by the finding that highly variable clinical response is correlated with pharmacokinetic (PK) variability. Serum Trough Concentrations (TCs) of the drug are measured and dosage regimens are adapted in order to achieve target TCs that correlate with beneficial therapeutic outcomes. The TC concept is relatively simple but gives only a partial insight in PK. PK profiles should be interpreted in the light of patient specific influences (i.e., covariates) that explain variability.

Objective: Therefore, the aim of TDM must be to dose the biological in such a way that a personal optimal PK profile is achieved. Furthermore, currently used “treat-to-target” algorithms have proven to increase the therapeutic potential of the drugs, but dosage regimen adaptations are still robust guesswork.

Results: A clinical decision support tool for accurately forecasting drug exposure would significantly impact TDM and is suggested to promote successful implementation of individualized predictive treatment in clinical practice.

Conclusion: This review provides a clinician-oriented overview of the state-of-the-art, the gaps in current knowledge and future potential of individualized predictive treatment.

Keywords: Anti-integrin, inflammatory bowel disease, immunogenicity, pharmacokinetics, trough concentration, therapeutic drug monitoring, modeling, tumor necrosis factor-alpha.

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Article Details

VOLUME: 19
ISSUE: 7
Year: 2018
Page: [757 - 776]
Pages: 20
DOI: 10.2174/1389450117666160307144329
Price: $65

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