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

  • Christopher Ma
  • Robert Battat
  • Vipul Jairath
  • Niels Vande CasteeleEmail author
Inflammatory Bowel Disease (G Lichtenstein, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Inflammatory Bowel Disease
  2. Topical Collection on Inflammatory Bowel Disease

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.

Keywords

Biologics Crohn’s disease Inflammatory bowel disease Therapeutic drug monitoring Thiopurines Ulcerative colitis 

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

Notes

Authorship 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.

Funding Support

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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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Christopher Ma
    • 1
    • 2
  • Robert Battat
    • 2
    • 3
  • Vipul Jairath
    • 2
    • 4
    • 5
  • Niels Vande Casteele
    • 2
    • 6
    Email author
  1. 1.Division of Gastroenterology and HepatologyUniversity of CalgaryCalgaryCanada
  2. 2.Robarts Clinical Trials, Inc.LondonCanada
  3. 3.Division of GastroenterologyUniversity of California San DiegoLa JollaUSA
  4. 4.Department of Medicine, Division of GastroenterologyWestern UniversityLondonCanada
  5. 5.Department of Epidemiology and BiostatisticsWestern UniversityLondonCanada
  6. 6.Department of MedicineUniversity of California San DiegoLa JollaUSA

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