Christopher Ma1,2, Robert Battat2,3, Vipul Jairath2,4,5, Niels Vande Casteele6,7. 1. Division of Gastroenterology and Hepatology, University of Calgary, 3280 Hospital Drive NW, Calgary, Alberta, T2N 4Z6, Canada. 2. Robarts Clinical Trials, Inc., #200, 100 Dundas Street, London, Ontario, N6A 5B6, Canada. 3. Division of Gastroenterology, University of California San Diego, 9500 Gilman Drive, #0956, La Jolla, CA, 92093, USA. 4. Department of Medicine, Division of Gastroenterology, Western University, #200, 100 Dundas Street, London, Ontario, N6A 5B6, Canada. 5. Department of Epidemiology and Biostatistics, Western University, #200, 100 Dundas Street, London, Ontario, N6A 5B6, Canada. 6. Robarts Clinical Trials, Inc., #200, 100 Dundas Street, London, Ontario, N6A 5B6, Canada. nvandecasteele@ucsd.edu. 7. Department of Medicine, University of California San Diego, 9500 Gilman Drive, #0956, La Jolla, CA, 92093, USA. nvandecasteele@ucsd.edu.
Abstract
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. RECENT FINDINGS: 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.
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. RECENT FINDINGS: 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.
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