Over the last several decades, therapeutic monoclonal antibodies (t-mAbs) have proven to be indispensable biopharmaceutical agents in treating a variety of conditions from various cancers to autoimmune diseases.

In today's session, “Immunogenicity of Therapeutic Monoclonal Antibodies: Analytical and Clinical Perspectives,” speakers Niels Vande Casteele, PharmD, Maria Alice Willrich, PhD, and Melissa Snyder, PhD, will present on three evolving areas of t-mAbs: clinical complications with t-mAbs as drugs, with emphasis in the field of inflammatory bowel disease; analytical considerations in therapeutic monitoring of t-mAbs; and challenges with interpreting test results.

Willrich and Snyder believe laboratorians will continue to see growth in the number of approved t-mAbs, as well as in the number of indications for their use. And they will elucidate how the availability of biosimilars is likely to disseminate these therapies further. This poses new challenges for laboratorians, for while t-mAbs are effective therapeutics, they can also cause unintended responses, such as the formation of anti-drug-antibodies (ADAs). This is a leading cause of therapeutic failure with t-mAbs.

The speakers will also discuss how t-mAbs such as infliximab and adalimumab are anti-tumor necrosis factors (TNF) that have been highly successful in treating inflammatory bowel disease (IBD). Nevertheless, a significant percentage of patients are either primary non-responders or lose response over time. When this happens, it can be difficult for clinicians to determine next steps. Loss of response may be reconciled in several ways, including increasing the dose, changing the drug to another anti-TNF t-mAb or an entirely new class of drugs, or adding an immunomodulator to the treatment regimen.

The speakers will note that in order to guide the next course of action, laboratories are critical in determining the mechanism behind treatment failure. The primary reason for no response or loss of response is the development of ADA, but subtherapeutic drug levels or an inflammatory process unrelated to the targeted pathway could also be responsible. This is why therapeutic drug monitoring (TDM) is so important in identifying the presence of ADA and the drug level before making drastic changes to the therapeutic regimen.

The speakers will also discuss how TDM indications come with their own caveats. Detection of ADA does not always correlate with drug inefficacy—ADAs may be transient or persistent. They are classified based on how they impact the function of the therapeutic monoclonal antibody. The speakers also plan to clarify that it is not clinically useful to measure t-mAb quantitation or anti-drug-antibodies for every patient.

Other aspects that the speakers will discuss include the differences among various methods, between-method variation, and lack of a defined cut-off for each method that correlates to clinical outcome. The speakers will also delve into the ways ADAs affect pharmacokinetics and clinical outcomes and how labs of different sizes can make the decision about which method to use and when to perform in-house versus send-out tests. All of these considerations are essential for laboratories to evaluate, particularly as the use of t-mAbs increases with the ever-increasing availability of targeted therapies.