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

  • Inflammatory Bowel Disease (G Lichtenstein, Section Editor)
  • Published:
Current Treatment Options in Gastroenterology Aims and scope Submit manuscript

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.

Summary

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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Abbreviations

ADAb:

anti-drug antibody

AGA:

American Gastroenterological Association

BMI:

body mass index

CD:

Crohn’s disease

CDAI:

Crohn’s Disease Activity Index

CI:

confidence interval

CRP:

C-reactive protein

DIS:

dose intensification strategy

ECLIA:

electrochemiluminescence immunoassay

ELISA:

enzyme-linked immunosorbent assay

FC:

fecal calprotectin

HMSA :

homogeneous mobility shift assay

HR:

hazard ratio

IBD:

inflammatory bowel disease

IL:

interleukin

JAK:

Janus kinase

PK:

pharmacokinetic

RGA:

reporter gene assay

ROC:

receiver operating characteristic

TDM:

therapeutic drug monitoring

TNF:

tumor necrosis factor

TPMT:

thiopurine methyltransferase

UC:

ulcerative colitis

6-TGN:

6-thioguanine nucleotides

References and Recommended Reading

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Funding

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.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, University of Calgary, 3280 Hospital Drive NW, Calgary, Alberta, T2N 4Z6, Canada

    Christopher Ma MD

  2. Robarts Clinical Trials, Inc., #200, 100 Dundas Street, London, Ontario, N6A 5B6, Canada

    Christopher Ma MD, Robert Battat MD, Vipul Jairath MD, PhD & Niels Vande Casteele PharmD, PhD

  3. Division of Gastroenterology, University of California San Diego, 9500 Gilman Drive, #0956, La Jolla, CA, 92093, USA

    Robert Battat MD

  4. Department of Medicine, Division of Gastroenterology, Western University, #200, 100 Dundas Street, London, Ontario, N6A 5B6, Canada

    Vipul Jairath MD, PhD

  5. Department of Epidemiology and Biostatistics, Western University, #200, 100 Dundas Street, London, Ontario, N6A 5B6, Canada

    Vipul Jairath MD, PhD

  6. Department of Medicine, University of California San Diego, 9500 Gilman Drive, #0956, La Jolla, CA, 92093, USA

    Niels Vande Casteele PharmD, PhD

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Contributions

CM, RB, VJ, and, NVC contributed to the study design, manuscript drafting, and manuscript editing. All authors approve the final version of the manuscript.

Corresponding author

Correspondence to Niels Vande Casteele PharmD, PhD.

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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.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Inflammatory Bowel Disease

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Ma, C., Battat, R., Jairath, V. et al. Advances in Therapeutic Drug Monitoring for Small-Molecule and Biologic Therapies in Inflammatory Bowel Disease. Curr Treat Options Gastro 17, 127–145 (2019). https://doi.org/10.1007/s11938-019-00222-9

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