Advances in Therapeutic Drug Monitoring for Small-Molecule and Biologic Therapies in Inflammatory Bowel Disease
Purpose of review
Therapeutic drug monitoring (TDM) is increasingly utilized as a strategy to optimize inflammatory bowel disease (IBD) therapeutics. As management paradigms have evolved towards treat-to-target strategies, there has been growing interest in expanding the role of TDM to guide drug optimization for achieving objective endpoints. This review summarizes the evidence for using TDM with biologic and oral small-molecule therapies, evaluates the role of reactive versus proactive TDM in treatment algorithms, and identifies potential future applications for TDM.
Achieving therapeutic drug concentrations has been associated with important clinical, endoscopic, and histologic outcomes in IBD. However, the optimal drug concentration varies by therapeutic agent, disease phenotype, inflammatory burden, phase of treatment, and target outcome. Traditionally, TDM has been used reactively to define pharmacokinetic versus mechanistic failures after loss of response to a tumor necrosis factor-α (TNF) antagonist and while observational data suggests a benefit to proactive TDM, this has not been definitively confirmed in prospective randomized controlled trials. The role of TDM in optimizing vedolizumab, ustekinumab, and tofacitinib remains unclear, given differences in pharmacokinetics and immunogenicity compared to TNF antagonists. Measuring drug action at the site of inflamed tissue may provide additional insights into treatment optimization.
The use of TDM offers the possibility of a more personalized treatment approach for patients with IBD. High-quality studies are needed to delineate the role of proactive TDM for maintaining remission, for optimizing induction regimens, and for novel agents.
KeywordsBiologics Crohn’s disease Inflammatory bowel disease Therapeutic drug monitoring Thiopurines Ulcerative colitis
American Gastroenterological Association
body mass index
Crohn’s Disease Activity Index
dose intensification strategy
enzyme-linked immunosorbent assay
homogeneous mobility shift assay
inflammatory bowel disease
reporter gene assay
receiver operating characteristic
therapeutic drug monitoring
tumor necrosis factor
CM, RB, VJ, and, NVC contributed to the study design, manuscript drafting, and manuscript editing. All authors approve the final version of the manuscript.
Dr. Christopher Ma is supported by a Clinician Fellowship from the Canadian Institutes of Health Research and the Canadian Association of Gastroenterology. Dr. Niels Vande Casteele is supported by a Research Scholar Award from the American Gastroenterological Association.
Compliance with Ethical Standards
Conflict of Interest
Christopher Ma and Robert Battat have no conflicts of interest to declare.
Vipul Jairath has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena pharmaceuticals, Genetech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Robarts Clinical Trials, Topivert, and Celltrion, and speaker’s fees from Takeda, Janssen, Shire, Ferring, Abbvie, and Pfizer.
Niels Vande Casteele has received grant/research support from R-Biopharm and Takeda, and consulting fees from Pfizer, Progenity, Prometheus, and Takeda.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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