Advances in Therapeutic Drug Monitoring for Small-Molecule and Biologic Therapies in Inflammatory Bowel Disease.

Abstract

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.