Therapeutic Drug Monitoring (TDM) of TNFα blockers
TNFα blockers are biologic agents which are used for the treatment of inflammatory diseases such as ulcerative colitis, Crohn’s disease and rheumatoid arthritis. Infliximab (IFX, Remicade®, RemsimaTM, Inflectra®) as well as adalimumab (Humira®) belong to this group of drugs.
How do TNFα blockers function?
When
an inflammation starts, cells of the immune system increase the
production of TNFα (see figure 1). TNFα binds to specific receptors,
which trigger the signal for the inflammatory process.
In case of chronic inflammation the immune system continuously produces TNFα, so that the inflammation does not cease. TNFα blockers interrupt this circle by binding to the messenger TNFα. Hereby the molecule can no longer bind to the receptor, so that the signaling cascade of the inflammatory process is interrupted.
As a result the inflammation and its symptoms can decrease or cease.
Individual dose adjustment by measuring drug levels and immunogenicity
In
order for TNFα blockers to work optimally it is important to check
their trough level on a regular basis, since the bioavailability differs
from person to person. The trough level (TL) is defined as the drug
concentration in the blood measured right before the next infusions (see
Figure 2).
Moreover, immunogenicity has an impact of the efficacy of the drug. So called anti-drug antibodies (ADA) bind to the drug and can lead to a decrease in drug availability in the metabolism as well as to allergic reactions.
Monitoring of drug- and anti-drug-antibody-levels of TNFα blockers helps to optimally adjust the therapy to the individual needs of the patient.
Therapy adjustment based on therapeutic drug monitoring
The
TAXIT-Algorithm (TAXIT = Trough Concentration Adapted Infliximab
Treatment, Figure 3) is a recommendation for therapy adaptation based on
the results of through- and anti-drug-antibody-levels of Infliximab.
It is a result of the study by Nils Vande Casteele et al. (KU Leuven) which investigated the effect of drug monitoring on the outcome of TNFα-treatment.
The study shows the positive effect of TDM for therapy optimization and treatment cost reduction. Moreover it indicates, that testing for anti-drug antibodies does not have to be performed on a standard basis but only in
patients with undetecteable trough level of infliximab (see Figure 3). RIDASCREEN® IFX Monitoring and RIDASCREEN® Anti-IFX Antibodies are based on the assays used in this study.
Therapeutic Drug Monitoring of Infliximab (Remicade®) and Adalimumab (Humira®)
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