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Factors Influencing Drug Disposition of Monoclonal Antibodies in Inflammatory Bowel Disease: Implications for Personalized Medicine

  • Pavine L. C. Lefevre
  • Lisa M. Shackelton
  • Niels Vande CasteeleEmail author
Leading Article

Abstract

Monoclonal antibody (mAb) therapies have revolutionized the treatment of several chronic inflammatory diseases, including the inflammatory bowel diseases (IBD), Crohn’s disease, and ulcerative colitis. While efficacious, responses to these therapies vary considerably from patient to patient, due in part to inter- and intra-individual variability in pharmacokinetics (PK) and drug exposure. The concept of personalized medicine to monitor drug exposure and to adjust dosing in individual patients is consequently gaining acceptance as a powerful tool to optimize mAb therapy for improved outcomes in IBD. This review provides a brief overview of the different mAbs currently approved or in development for the treatment of IBD, including their presumed mechanisms of action and PK properties. Specifically described are (1) the factors known to affect mAb PK and drug exposure in patients with IBD, (2) the value of population PK/pharmacodynamic (PD) modeling to identify and understand the influence of these factors on drug exposure and effect, and (3) the clinical evidence for the potential of therapeutic drug monitoring (TDM) to improve IBD outcomes in response to mAb-based therapy. Incorporation of PK/PD parameters into clinical decision support tools has the potential to guide therapeutic decision making and aid implementation of personalized medicine strategies in patients with IBD.

Notes

Compliance with Ethical Standards

Conflict of interest

PLCL and LMS have nothing to disclose. NVC reports research support from R-Biopharm and Takeda and consulting fees from Boehringer Ingelheim, Janssen, Pfizer, Progenity, Prometheus, and Takeda, outside of the submitted work.

Funding

NVC holds a Research Scholar Award form the American Gastroenterological Association (AGA).

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Robarts Clinical Trials, Inc.LondonCanada
  2. 2.Division of Gastroenterology, Department of Medicine, School of Medicine, IBD CenterUniversity of California San DiegoLa JollaUSA

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