Better outcomes than reactive TDM
By Loren G. Rabinowitz, MD; Konstantinos Papamichael, PhD, MD; and Adam S. Cheifetz, MD, AGAF
Therapeutic drug monitoring (TDM), or the practice of treatment optimization based on serum drug concentrations, is used in many settings, including solid organ transplantation, infection, and immune-mediated inflammatory diseases, including inflammatory bowel disease (IBD). In IBD, the use of TDM has been an area of keen research focus, and, in our view, should be standard practice for optimization of biologic therapy, particularly in the setting of anti–tumor necrosis factor (TNF) therapy. TDM has demonstrated utility in determining the correct timing and dosage of biologics and can provide the impetus for deescalating or discontinuing a biologic in favor of an alternative one. It also allows prescribers the ability to protect patients from severe infusion reactions if they have developed anti-drug antibodies (ADAs).
Dr. Loren G. Rabinowitz
Reactive TDM refers to a strategy of assessing drug concentration and presence of ADAs in the setting of primary nonresponse (PNR) and loss of response (LOR) to a biologic agent. In this context, TDM informs possible reasons for loss or lack of response to treatment – for example, insufficient drug concentration or the development of high-titer ADAs (immunogenicity) – thus better directing the management of these unwanted outcomes.1 Insufficient anti-TNF concentrations have been associated with PNR and lack of clinical remission at 1 year in patients with IBD,2 which underscores the need for a durable strategy to ensure appropriate drug concentrations from the induction through maintenance phases of biologic administration. Reactive TDM can also be used to inform the decision to abandon a particular therapy in favor of a different biologic and to guide the selection of the next biologic agent, and has been shown to be less expensive than empiric dose escalation.2 With regard to infliximab and adalimumab, it is our practice to continue dose escalation until drug concentrations are above 10-15 mcg/mL prior to abandoning therapy.1
Dr. Konstantinos Papamichael
For a significant number of patients, reactive TDM identifies at-risk patients too late, when ADAs have already formed. Because the number of medications to treat IBD remains limited, waiting for a patient to lose response to an agent, particularly anti-TNF therapies, increases the likelihood of immunogenicity, thus rendering an agent unusable. Proactive TDM or checking drug trough concentrations preemptively and at predetermined intervals, and dosing to an appropriate concentration, can improve patient outcomes. If drug concentration is determined to be not “at target,” dosage and timing of administration can be increased with or without the addition of an immunomodulator (thiopurines or methotrexate) to optimize the biologic’s efficacy and prevent immunogenicity. This approach allows the provider to anticipate and proactively guard against PNR and future LOR.
