Biologic Therapeutic Drug Monitoring: Drug, Anti-drug Antibody Inform Personalized Decisions in Gastroenterology & Rheumatology

Biologic drug therapies have proven to be precious in the treatment of inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and other immune-mediated diseases — due to not only their high financial cost but also their finite number and variable longevity. Approved biologic drugs to treat inflammatory bowel disease and/or rheumatoid arthritis include monoclonal antibodies against integrin (vedolizumab and natalizumab), interleukin 12 and 23 (ustekinumab), and TNF (infliximab, adalimumab, golimumab, certolizumab, etanercept and the biosimilars, infliximab-abda and infliximab-dyyb).

Biologic drugs are prime candidates for therapeutic drug monitoring (TDM) because they are very expensive, relatively few, subject to wide pharmacokinetic variability, and unfortunately, significant primary and secondary failure rates. As these biologic drugs comprise a staggering healthcare cost (Humira®, Remicade®, and Stelara® gross $31 billion in 2018), we consider how the use of these precious medications might be optimized by biologic therapeutic drug monitoring.

The clinical value of therapeutic drug monitoring is predicated on the existence of a parallel relationship between measurements of drug (or antibody) in patient sample and outcomes. In the case of biologic drugs, therapeutic drug monitoring also implies the detection and quantitation of anti-drug antibodies. The anti-drug antibody measurement together with the concomitant free drug level provides critical pharmacokinetic and immunogenic assessment that cannot be otherwise be ascertained clinically.

Here, we discuss the application of biologic therapeutic drug monitoring to inform and expedite personalized clinical decision-making, such as:

• Patient-specific dose titrating to target or maximally beneficial concentrations
• Diagnosing of immunogenicity
• Determining co-therapies and biologic switching
• Improving longevity of therapy
• Reducing drug waste and overall healthcare costs
• Supporting proactive management

Furthermore, recent data show that some patients with secondary failure due to immunogenicity may recapture clinical response as a result of treating away existing anti- drug antibodies. We will discuss why it is critical for clinicians to scrutinize their choice of therapeutic drug monitoring for biologic drugs and their anti-drug antibodies, and which assays provide the requisite sensitivity, resolution and precision to detect early immunogenicity and reliably monitor meaningful changes in titers.

At its best, biologic drug therapeutic drug monitoring gives clinicians the means not only to detect early, potentially-reversible immunogenicity, but also to monitor rising and receding titers.

Speakers

Dr Jane Yang, Director of Medical Science at Esoterix Laboratory Services, part of the LabCorp Specialty Testing Group

Dr. Yang is a graduate of Massachusetts Institute of Technology and Harvard Medical School (Health Sciences and Technology Society). She is a clinical pathologist formerly of Massachusetts General Hospital where she practiced, taught, and authored in basic science, toxicology, pharmacokinetics, and laboratory medicine. At LabCorp, Dr. Yang works closely with scientists at Esoterix, a LabCorp Center of Excellence, and expert clinicians on various research and development projects to validate specialized assays, investigate their clinical usefulness, and provide understandable and actionable diagnostic data.

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Dr Kelly Chun, Vice President and Scientific Director of Esoterix/Endocrine Sciences, part of the LabCorp Specialty Testing Group

Since joining Esoterix endocrinology as a technical director in 2002, Dr. Chun has held several leadership roles in laboratory management and R&D. Over the years, she developed and validated a number of pivotal endocrine and autoimmune tests for diagnostic use and pharmaceutical trials.  She brings more than 20 years of experience in protein assay development and offers scientific and strategic support across multi-disciplinary teams within LabCorp.

Dr. Chun earned her B.S. in Molecular Biology with a minor in Business Administration from University of Washington and her Ph.D. in Biochemistry from Medical College of Wisconsin. She completed her Postdoctoral Fellowship in Laboratory Medicine at Harvard Medical School.

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