Is There a Role for Therapeutic Drug Monitoring of Anti-TNF Monoclonal Antibodies in Inflammatory Bowel Disease

Abstract

In recent years it has become clear that therapeutic drug monitoring can be an important tool to optimize outcome and costs of anti TNF treatment including the subcutaneous and fully human monoclonal antibodies. There is a clear dose response curve between early serum concentrations of all monoclonal antibodies and response both short term and long term. The wide variations in early serum concentrations are insufficiently explained by classic pharmacokinetic factors. Low early concentrations can lead to anti-drug antibody formation and ensuing loss of response. Therapeutic drug monitoring allows to rationalize the current practice of dose optimization and the use of concomitant immunomodulator treatment. However more prospective studies are needed before strong recommendations can enter treatment guidelines.

Clinical Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Ulcerative Colitis

“…In contrast, low(er) concentrations have been demonstrated to be associated with the formation of antidrug antibodies (ADAs). Serum trough IFX concentrations at steady-state between 3 and 7 lg/ml have been related to improved clinical outcomes [9,138,[162][163][164][165][166][167][168][169][170].…”

“…Patients with acute extensive disease activity (Montreal classification E3) could potentially benefit from a top-down approach [7]. Therapeutic drug monitoring (TDM) is increasingly used in the treatment of UC to maximize the clinical benefit of therapeutic agents [8][9][10][11]. TDM is defined as measuring a drug concentration, interpreting this value using pharmacokinetic principles, followed by making decisions about possible dose adjustments or dosing intervals in order to optimize treatment [12].…”

Golimumab for moderate to severe ulcerative colitis

“…A clear association between serum concentrations of anti-TNF agents and the formation of antidrug antibodies has been demonstrated in patients with inflammatory bowel disease [17,18]. For IFX, the formation of antidrug antibodies is associated with lower serum IFX levels, infusion reactions, and loss of response [18].…”

“…Nowadays, it is more used as a tool for optimizing therapeutic outcomes and tailor therapies of individual patients [24]. The application of TDM in the mAb therapy has only been described recently [10,17,25,26]. For the proper application of TDM for GLM therapy, it is necessary to know the therapeutic range of the GLM serum concentration in different diseases, such as UC.…”

Dried blood samples can support monitoring of infliximab concentrations in patients with inflammatory bowel disease: A clinical validation

“…Therapeutic drug monitoring (TDM) can form an important tool to optimize efficacy of infliximab (IFX) treatment in patients with inflammatory bowel disease (IBD) . TDM for IFX in IBD patients is currently only applied in a reactive manner.…”