Treatment of Inflammatory Bowel Disease with Biologics

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Employing Drug Level and Antibody Data in Clinical Care:

Therapeutic Drug Monitoring

With data demonstrating the association between drug levels and antibody concen-
trations with response to medical therapy, several studies have assessed the impact
of therapeutic drug monitoring (TDM) on clinical outcomes in IBD. In general, there
are two potential approaches to employing these laboratory tests [ 42 ]. “Reactive
TDM” refers to the utilization of drug levels and antibodies in response to changes
in the clinical status of the patient receiving biologic therapy. When a patient has an
increase in symptoms or non-response, these assays are then employed to determine
if the patient would potentially benefit from modification of the current biologic
dose, changing to another anti-TNF, or switching to an alternative class of medica-
tion. “Proactive TDM” refers to the use of these assays at specific time points in
therapy to ensure that the dose is optimized, prior to loss of response or non- response,
with the goal of achieving “therapeutic” trough drug levels to possibly prevent flares
of disease. Several studies have assessed these two approaches and will be reviewed.
A standardized algorithm has been developed to guide clinicians in the interpre-
tation of anti-TNF drug level and antibody results (Fig. 8.1). In this example of
reactive monitoring, the initial step is determining that active mucosal inflammation
is present, ensuring that the symptoms being treated are not related to other etiologies,

Patient with clinical

symptoms on an Anti-TNF*

Measure drug levels

and anti-drug antibodies

Therapeutic drug level,

No or Low Abs

Switch to medication with
alternative mechanism,
such as anti-integrin

Appropriate course

currently unknown

Increase dose or decrease

dosing interval of anti-TNF

*With documented active inflammation

Switch to another anti-TNF

if available, or if not then

to a medication with an

alternate mechanism of action

Therapeutic drug level,

High level Abs

subtherapeutic drug level,

No or Low Abs

subtherapeutic drug level,

high level antibodies

Fig. 8.1 Measurement of anti-TNF drug levels and anti-drug antibodies can yield one of four
potential combinations, dependent on the concentration of each. Appropriate interpretation of
these results allows clinicians to either optimize the current medication or change to an alternative
medication while maximizing the potential clinical benefit

F.I. Scott and M.T. Osterman