5 Questions About Therapeutic Drug Monitoring in IBD

The American Gastroenterological Association (AGA) released guidelines on therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD)¹ in 2017. However, best practices regarding the use of TDM, an approach that may help optimize the drug concentration and clinical improvements of patients with IBD, remain unclear. 

Gastroenterology Consultant caught up with Siddharth Singh, MD, MS, an assistant professor of medicine in the division of gastroenterology at the University of California San Diego, about when and how gastroenterologists should use TDM in IBD, a topic he will further discuss at the AIBD Regional Meeting in Los Angeles. 

Gastroenterology Consultant: Since the 2017 release of the AGA guidelines, what advances have been made in bridging any knowledge gaps surrounding TDM?

Siddharth Singh: One of the key knowledge gaps mentioned in the 2017 guidelines was related to the role of proactive TDM in the management of IBD. While there have been no landmark clinical trials to inform the evidence for proactive TDM, several published and ongoing studies are evaluating this question, and we hope to have more insight on this in the guideline update, which I anticipate in the next 3 to 4 years, hopefully as higher quality data comes along. In addition, the role of TDM for other non-tumor necrosis factor (TNF)-targeting biologics, like vedolizumab and ustekinumab, is also being studied, and we hope to have more information on this as well. 

GASTRO CON: In your opinion, what is the most significant drawback to proactive and reactive TDM? 

SS: For proactive TDM, there is a lack of well-conducted prospective studies that evaluate appropriate implementation and effectiveness of TDM in real-world community practices. There is limited information on optimal trough concentrations and, more importantly, significance of “incidentally” detected anti-drug antibodies. Most gastroenterologists who use this sparingly may find it difficult to appropriately interpret and implement this into practice, which could lead to inappropriate treatment changes in otherwise stable patients.

For reactive TDM, there is a lack of high-quality evidence on adequate target trough concentrations and what is considered high vs low-titer anti-drug antibodies, particularly for drugs other than infliximab. It is important to recognize that optimal target trough concentrations are dynamic depending on the disease state, outcome of interest, and timing of assessment. 

GASTRO CON: What clinical-decision support tools are available for gastroenterologists to help determine whether to use TDM?

SS: The AGA has published a clinical decision support tool to implement TDM for anti-TNF agents in practice. In addition, the Building Research in Inflammatory Bowel Disease Globally (BRIDGe) group also has an online biologic therapy optimizer tool² to help guide clinicians on how to address the results of anti-TNF concentration and antibody testing, since there is no consensus on how to interpret these for various clinical scenarios.

GASTRO CON: What is a common misconception about TDM for IBD you have heard among your peers?

SS: The most common misconception is that presence of any titer of anti-drug antibodies is bad and warrants a change in treatment. It is important to recognize that antibody assays are different, with some being more sensitive than others. Persistent, high-titer anti-drug antibodies are clinically meaningful, whereas transient, low-titer antibodies may have limited clinical relevance.

GASTRO CON: What are the main barriers to the implementation of TDM that health care practitioners are currently facing?

SS: Practitioners are unsure whether the cost of assessing drug concentration and anti-drug antibodies will be covered by insurance and worry about out-of-pocket costs for patients. Different companies are offering discounted prices for these assays, but patients and providers need to jump through several hoops to get those lower prices. One good way to increase uptake might be companion diagnostics, wherein each new biologic start is accompanied by the ability to perform these assays and make treatment modifications.

References:

1. Feuerstein JD, Nguyen GC, Kupfer SS, et al. American Gastroenterological Association institute guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology. 2017;153(3):827-834. https://doi.org/10.1053/j.gastro.2017.07.032.

2. Biologic Therapy Optimizer. https://www.bridgeibd.com/biologic-therapy-optimizer. Accessed March 22, 2019. 

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