Inflammatory Bowel Disease
Publication Date: September 1, 2017
Key Points
Key Points
Inflammatory bowel disease (IBD) is often treated with immunomodulators and/or biologics.
The trough concentrations of these drugs can vary due to disease severity, phenotype, degree of inflammation, use of immunomodulator, patient sex, and body mass index, as well as variability in drug clearance through immune and non-immune-mediated mechanisms.
In order to better optimize the drug concentration and clinical improvement, therapeutic drug monitoring (TDM) is used to check the drug trough concentration and assess for the presence of anti-drug antibodies.
TDM can be performed at any point during induction or maintenance therapy.
In the event of drug failure, there are 3 possible causes:
Mechanistic failure occurs when the patient is not responding despite optimal drug trough concentrations.
This type of failure is likely related to the disease process being driven by inflammatory mediators that are not blocked by the particular drug. Therefore, these patients are unlikely to respond to other drugs within the same class.
Non-immune-mediated pharmacokinetic failure occurs when patients do not adequately respond to therapy in the setting of subtherapeutic trough concentrations and absence of anti-drug antibodies.
This phenomenon results from rapid drug clearance, often in the setting of a high inflammatory burden.
Immune-mediated pharmacokinetic failure occurs in patients who have low or undetectable trough concentrations and high titers of anti-drug antibodies.
This type of drug failure results from the immune-mediated formation of neutralizing anti-drug antibodies.
The trough concentrations of these drugs can vary due to disease severity, phenotype, degree of inflammation, use of immunomodulator, patient sex, and body mass index, as well as variability in drug clearance through immune and non-immune-mediated mechanisms.
In order to better optimize the drug concentration and clinical improvement, therapeutic drug monitoring (TDM) is used to check the drug trough concentration and assess for the presence of anti-drug antibodies.
TDM can be performed at any point during induction or maintenance therapy.
In the event of drug failure, there are 3 possible causes:
Mechanistic failure occurs when the patient is not responding despite optimal drug trough concentrations.
This type of failure is likely related to the disease process being driven by inflammatory mediators that are not blocked by the particular drug. Therefore, these patients are unlikely to respond to other drugs within the same class.
Non-immune-mediated pharmacokinetic failure occurs when patients do not adequately respond to therapy in the setting of subtherapeutic trough concentrations and absence of anti-drug antibodies.
This phenomenon results from rapid drug clearance, often in the setting of a high inflammatory burden.
Immune-mediated pharmacokinetic failure occurs in patients who have low or undetectable trough concentrations and high titers of anti-drug antibodies.
This type of drug failure results from the immune-mediated formation of neutralizing anti-drug antibodies.
Treatment
...atment...
...adults with active IBD treated with anti-T...
...dult patients with quiescent IBD treated with anti...
...patients with IBD being started on thiopurine...
...t patients treated with thiopurines with act...
...patients with quiescent IBD treated with t...
...ed Target Trough Concentrations When Applying...