Q&A: Navigating Proactive, Reactive TDM in a Private Practice Setting
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Differentiating patients with inflammatory bowel disease who have lost response to a biologic used to be considered a “gray zone,” according to Sushama Gundlapalli, MD, MS, a board-certified gastroenterologist at Suburban Gastroenterology Ltd. in Naperville, Illinois.
But, according to Gundlapalli, the introduction of therapeutic drug monitoring (TDM) has helped clarify a patient’s clinical picture as being a mechanistic or pharmacokinetic failure, guiding us to direct therapies in a more targeted way.
“We have been steadily increasing our reactive drug monitoring in the last 2 to 3 years, but the concept of proactive monitoring is slowly but cautiously gaining support over the last year or so,” Gundlapalli told Healio Gastroenterology and Liver Disease.
In this month’s cover story, multiple gastroenterologists from large academic institutions discuss the nuances of TDM.
We spoke with Gundlapalli about TDM to get a private practice physician’s perspective on the process of monitoring a patient’s response to therapy. – by Ryan McDonald
Q: Does the added cost and time related to performing TDM make it difficult for GIs in private practice?
Gundlapalli: First of all, from a practical perspective, we have had to determine which of our local labs are offering the various drug levels and at what cost. For example, a majority of our local labs were offering infliximab and adalimumab levels, but not vedolizumab or ustekinumab. Some were being performed locally and some were being sent out to ARUP or Mayo Labs making the turn-around times variable. Prometheus, a specialty lab, is also offering mobile nursing and the ability to do in-home blood draws.
Second, not all commercially available drug assays are considered equal. We have had to familiarize ourselves with the ideal assay depending on what clinical question we are looking to answer. For example, if one is looking to tweak trough levels, any of the assays should be adequate but if there is concern about antibody production, the ELISA may not be as reliable as liquid phase mobility shift technology (Prometheus).
Third, is cost. Although the pricing for these tests has been reduced considerably over the past few years, depending on a patient’s insurance carrier and deductible, their out of pocket expense can vary from just under a $100 to several hundreds. We have reached out to four of our locally available laboratories to outline their current pricing schedules. Ultimately, we have asked patients to contact their insurance companies to clarify their out of pocket cost. Some of the insurance carriers are still considering these tests “experimental,” necessitating letters of appeal that review available guidelines and clinical trials.
Although these factors can be a deterrent, the clinical benefit of TDM in providing an objective approach to loss of response to biologic therapy has, in my opinion, outweighed the practical roadblocks.
Q: Which type of monitoring, particularly for private practices, is easier to perform?
Gundlapalli: Reactive drug monitoring is a little easier to conceptualize and navigate. In a patient having evidence of ongoing disease activity, whether it be symptomatic, endoscopic or histologic, the presence and degree of drug level, and/or antibodies is helpful in choosing between a change in class of drug vs. dose adjustment. I think most of us would consider this a “no-brainer”.
The concept of proactive monitoring is more controversial. This refers to checking drug levels early in the course of drug, or periodically in patients in clinical remission, to help identify early mechanistic non-responders, or predict future loss of response. This is still not universally utilized due to multiple reasons.
One, the data supporting this approach are accumulating but remains insufficient. Second is the fear that insurance companies are considering this approach more “experimental” than the standard reactive monitoring. Three, many practitioners are still reluctant to change therapy in a patient who is clinically doing well and has had a fairly benign course of disease. I would be more apt to consider proactive monitoring in patients with a more complex disease course, e.g., those with multiple drug failures or severe disease requiring hospitalizations or surgery. I think it’s safe to say that most of us are more selective with the proactive approach.
Q: What is the main concern with proactive TDM?
Gundlapalli: One of the concerns is a lack of consistent data. How often does this approach actually result in a change in clinical outcomes, and how often does it actually lead to a change in disease course? Many of our patients with IBD are living with an expensive disease, and this definitely adds to their economic burden. I often discuss the cost factor as part of shared decision making and let the patient’s preference weigh in on the choice to pursue testing. Future studies will hopefully provide more information to guide us.
Q: What advice would you offer other private practice physicians who might not be as familiar with TDM, but would like to incorporate it into practice?
Gundlapalli: Therapeutic targets in IBD have evolved over the last few decades. The majority of recent research has helped us understand that a more aggressive monitoring of clinical response, using mucosal healing and fecal biomarkers rather than symptoms alone, can improve long-term outcomes. This more diligent approach has increased our recognition of patients with sub-clinical disease activity, who previously would have been labeled as being in remission. This, in turn, is leading us to question the optimization of their biologic therapy, resulting in increased use of reactive drug monitoring.
It is important to be aware of the different assays being offered in your local community, and to be informed of the cost to the patient. Also, when tracking or comparing values, we need to make sure that they are from the same laboratory with a consistent assay.
I would also be cautious with interpretation of antibody levels and titers, as they can be transient and non-neutralizing, and vary greatly among assays. This is different from drug levels that are more reproducible across assays. A drug tolerant assay such as Prometheus is considered more reliable with antibody measurement and may be the appropriate choice if you are considering a change in drug based on antibody formation.
Due to continued variability in insurance coverage, be prepared to defend your use of the drug monitoring with letters of appeal, both in reactive and proactive scenarios.
Ultimately, management of IBD and in particular the use of therapeutic drug monitoring is both art and science. It is often not solely based on available evidence and societal guidelines, but also on the clinician’s experience and patient preference.
Disclosure: Gundlapalli reports no relevant financial disclosures.