A guide to the benefits of therapeutic drug monitoring
What is therapeutic drug monitoring?
Therapeutic drug monitoring (TDM) measures specific drugs in a patient’s bloodstream over time, which is important for developing long term individualised care plans for patients with chronic inflammatory diseases such as inflammatory bowel disease (IBD) and rheumatoid arthritis.
- TDM helps to achieve a consistent concentration of the drug in the blood, maximising the clinical benefit, and minimising potential side effects.
- TDM has grown in use over the last decade, particularly with difficult-to-manage medications, such as those with narrow therapeutic ranges or with a poor correlation between dose and clinical effect (high pharmacokinetic variability).
- The clinical benefits of TDM represent a significant development towards the goal of offering personalised medicine.
Understanding anti-drug antibodies
The natural course of chronic inflammatory diseases often presents a number of challenges to the treating clinician, and an adequate response to treatment may not be achieved in all patients. Understanding anti-drug antibodies may shed some light on the issue, and helps to optimise patient management.
- Biologic medications such as anti-TNF (tumour necrosis factor) agents are frequently used to reduce inflammation in certain conditions.
- The immune systems of some patients treat anti-TNFs as a foreign protein and form anti-drug antibodies (ADAs). This can happen straightaway (primary non-response) or after several months of treatment (loss of response), either way, it leads to failure.
- ADAs help clinicians to identify which patients will benefit most from a particular biologic therapy, so that they can determine the most effective management plan for each individual.
TDM in inflammatory bowel disease
Anti-TNFs reduce IBD activity and improve symptoms, but approximately 10-20 % of patients on these therapies develop ADAs either immediately, or after a period of positive response. Measuring antibody levels allows clinicians to keep a patient’s dose low, while still reducing disease activity and improving symptoms.
- TDM provides valuable insight into the possible causes of treatment failure and allows a better management strategy – some patients have marked disease activity and very few symptoms, which can lead to tissue destruction and even gut failure, while others have significant symptom history with no active disease present.
- Blood tests for TDM can be carried out remotely and therefore more frequently than the traditional annual patient review appointment, allowing gastroenterologists to monitor the response to the medication more closely.
- Research suggests that if ADAs form against one type of anti-TNF, then they will probably form against others too. Making an informed switch to other classes of medication earlier – rather than trying multiple anti-TNFs – accelerates positive outcomes for the patient and saves time and money for healthcare providers.
Measuring total vs free ADAs
Measuring the total number of ADAs (e.g. unbound, partially unbound and bound antibodies), gives a better understanding of the relationship between concentrations of the medication and the formation of ADAs.
- A rising titre of antibody can be treated as an early warning sign, allowing clinicians to intervene in a timely fashion, for example, changing treatment to an immunomodulated form of an anti-TNF.
- Higher doses of drug can be given to patients if they are not forming ADAs, and can be ruled out as an option for patients who are ADA-formers. Clinicians can make more informed decisions on low drug levels, dosage, and reasons for treatment failure.
- The presence of ADAs can cause immune-type symptoms, such as muscle ache and joint pains, in some cases mimicking the same symptoms caused by the disease. If only free ADAs are measured, it is not possible to be sure whether symptoms are disease related or caused by the immune response to ADAs.
Find out more about BIOHIT’s range of TDM assays at: www.biohithealthcare.co.uk/TDM.