Era of Personalized Medicine & Therapeutic Drug Monitoring in Autoimmune Diseases
Contributed Commentary by Aya Elhage
May 13, 2021 | The question “Is the medication I’m taking effective?” is of utmost importance for people with chronic autoimmune diseases. According to Johns Hopkins Medicine, approximately 10 million people in the United States are affected by autoimmune diseases. These diseases include inflammatory bowel disease (IBD), rheumatic diseases, and psoriasis and are all associated with tissue necrosis factor-alpha (TNF- α). TNF-α is an inhibitory cytokine produced by macrophages and can induce fever, inflammation, and cachexia, among other symptoms. As we continue to see, biologics, such as TNF-α inhibitors, are growing in popularity. As a pharmacist, this is one class of medications I regularly counsel my patients on. TNF-α inhibitors have been crucial in many diseases including IBD, psoriasis, cancer, and Alzheimer’s disease, among others. You may have heard of adalimumab (Humira) or infliximab (Remicade), but what exactly are we measuring to determine drug effectiveness and how can we, as clinicians, determine if these drugs are improving patient’s symptoms?
Therapeutic Drug Monitoring (TDM) Strategies
I have seen disproportions in disease burden and medication access due to the high cost and intravenous administration of TNF-α inhibitors. That’s why these medications are typically not first line options. Rather, they are given to patients with inadequate response to conventional medications, known as disease-modifying antirheumatic drugs (DMARDs), or to those with contraindications against these medications. Alternatively and more recently, cost-effective, FDA-approved biosimilar options for both adalimumab and infliximab, have entered the market.
Chronic autoimmune diseases are quite complex; patients are usually treated based on their symptoms because there are no cures yet available. To make matters more complicated, I have seen patients experience variable responses to treatments despite receiving similar doses at comparable dosing intervals. Varying patient response is due to pharmacodynamic and pharmacokinetic factors which often flux for various reasons. TDM strategies enable individualized and targeted monitoring to optimize drug dosage and dosing interval. When conducting TDM, the overall picture becomes clearer. As a healthcare provider, this helps the team understand drug effect variability and how it correlates with the reduction of symptoms. It is crucial to continue monitoring until an optimal concentration range is achieved. Once the optimal concentration is achieved, any further increase of the dose of adalimumab or infliximab no longer becomes beneficial, and unwanted side effects may arise.
It would be easy to monitor patients’ progress if the TNF-α inhibitor was the only medication they were on. However, this is often not the reality for most patients I’ve seen. What’s exciting about TDM is that it can be a valuable method for many other classes of medications (i.e., antibiotics, mood stabilizers, antiepileptics) due to their narrow therapeutic window. There is typically an optimal therapeutic range that indicates clinical effect or a clear reduction in symptoms. The two main reasons to monitor the therapeutic effect of drugs are to ensure effective therapy and evade toxicity.
Overcoming Treatment Failure
Treatment failure may occur and give patients a sense of disappointment and hopelessness. This brings us to the decision of discontinuing the medication due to loss of response or onset of serious adverse effects. We also don’t want to spend any more time or money on a medication that isn’t providing any benefit.
TDM serves as a guide to better serve our patients. What we don’t know yet is how much to increase or decrease the dose to change the outcomes related to chronic autoimmune diseases. In other words, we don’t know enough to say, “For every X mg, your symptoms will improve by X percent.” I have not come across data on this yet, but it would be exciting to see how patients would respond to understanding how the medication is positively or negatively impacting their health.
In my opinion, personalized medicine is the future of healthcare. Monitoring therapeutic levels of TNF-α inhibitors promotes individualized treatment while affirming that patients receive the most accurate and cost-effective regimen available. New laboratory diagnostics can unlock possibilities for clinicians can make effective adjustments based on quantitative results and can facilitate simplified decision-making with our patients for improved long-term response.
Aya Elhage, PharmD, MBA is a pharmacist with a passion for bridging the gap between diagnostics and treatment to transform the world of healthcare. Dr. Elhage currently serves as the Scientific Affairs Manager at EUROIMMUN US, a medical diagnostics company, supporting the team with commercial activities including scientific collaborations, scientific marketing, and business development of diagnostics.. She is also a registered pharmacist in both New York and California. She can be reached at firstname.lastname@example.org.
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