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Review
. 2021 Jul 27;27(8):1346-1355.
doi: 10.1093/ibd/izaa265.

Therapeutic Drug Monitoring of Tumor Necrosis Factor Antagonists in Crohn Disease: A Theoretical Construct to Apply Pharmacokinetics and Guidelines to Clinical Practice

Niels Vande Casteele  1 , Brian G Feagan  2 , Douglas C Wolf  3 , Anca Pop  4 , Mohamed Yassine  4 , Sara N Horst  5 , Timothy E Ritter  6 , William J Sandborn  1
Affiliations
Review

Therapeutic Drug Monitoring of Tumor Necrosis Factor Antagonists in Crohn Disease: A Theoretical Construct to Apply Pharmacokinetics and Guidelines to Clinical Practice

Niels Vande Casteele et al. Inflamm Bowel Dis. .

Abstract

Therapeutic drug monitoring (TDM) is the measurement of drug and antidrug antibody concentrations in individuals to guide treatment decisions. In patients with Crohn disease (CD), TDM, used either reactively or proactively, is emerging as a valuable tool for optimization of tumor necrosis factor (TNF) antagonist therapy. Reactive TDM is carried out in response to treatment failure, whereas proactive TDM involves the periodic monitoring of patients responding to TNF antagonist therapy to allow treatment optimization. In patients with CD, most of the available data for TDM relate to the first-to-market TNF antagonist infliximab and, to a lesser extent, to adalimumab and certolizumab pegol. Several gastroenterology associations, including the American Gastroenterology Association, have endorsed the use of reactive TDM in patients with active CD. However, fewer recommendations currently exist for the use of proactive TDM, although several new prospective randomized controlled trials evaluating proactive TDM strategies have been published. In this review, the current evidence for reactive and proactive TDM is discussed, and a proactive treatment algorithm for certolizumab pegol based on previously published threshold concentrations is proposed.

Keywords: antidrug antibody; certolizumab pegol; proactive TDM; reactive TDM; therapeutic drug monitoring.

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Figures

FIGURE 1.
FIGURE 1.
Comparison of 2 enzyme-linked immunosorbent (ELISA) assays for therapeutic drug monitoring in patients treated with certolizumab pegol: the LISA-TRACKER CZP assay* and a custom-made ELISA assay developed by UCB Pharma. Republished with permission of Future Science Ltd. on behalf of UCB Pharma, Copyright © 2017; permission conveyed through Copyright Clearance Center, Inc. Adapted with permission by Paul et al. *LISA-TRACKER is a product developed and manufactured by Theradiag, France. Miraca Life Sciences (now Inform Diagnostics) has a license to run these assays in the United States. CZP indicates certolizumab pegol; HRP, horseradish peroxidase; LLOQ, lower limit of quantification; PEG, polyethylene glycol; TMB, 3,3’,5,5’-tetramethylbenzidine; ULOQ, upper limit of quantification.
FIGURE 2.
FIGURE 2.
Proposed treatment approach for proactive TDM in clinical practice in patients in clinical remission receiving CZP maintenance therapy. aCZP cutoff concentrations based on Vande Casteele, Feagan, Vermeire, et al. CZP indicates certolizumab pegol.
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References

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