Therapeutic drug monitoring for current and investigational inflammatory bowel disease treatments

Scott D. Lee, Raina Shivashankar, Daniel Quirk, Haiying Zhang, Jean Baptiste Telliez, John Andrews, Amy Marren, Arnab Mukherjee, Edward V. Loftus

Research output: Contribution to journalReview articlepeer-review

Abstract

This article reviews therapeutic drug monitoring (TDM) use for current inflammatory bowel disease (IBD) treatments. IBD comprises Crohn's disease and ulcerative colitis-chronic gastrointestinal inflammatory disorders. Treatment options for moderate to severe IBD include thiopurines; methotrexate; biologic agents targeting tumor necrosis factor, α4β7integrin or interleukins 12 and 23; and Janus kinase inhibitors. TDM is recommended to guide treatment decisions for some of these agents. Published literature concerning TDM for IBD treatments was reviewed. S.D.L., R.S., and E.V.L. drew on their clinical experiences. Polymorphisms resulting in altered enzymatic activity inactivating thiopurine metabolites can lead to myelotoxicity and hepatotoxicity. Increased elimination of biologic agents can result from immunogenicity or higher disease activity, leading to low drug concentration and consequent nonresponse or loss of response. TDM may aid treatment and dose decisions for individual patients, based on monitoring metabolite levels for thiopurines, or serum drug trough concentration and antidrug antibody levels for biologic agents. Challenges remain around TDM implementation in IBD, including the lack of uniform assay methods and guidance for interpreting results. The Janus kinase inhibitor tofacitinib is not impacted by enzyme polymorphisms or disease activity, and is not expected to stimulate the formation of neutralizing antidrug antibodies. TDM is associated with implementation challenges, despite the recommendation of its use for guiding many IBD treatments. Newer small molecules with less susceptibility to patient variability factors may fulfill the unmet need of treatment options that do not require TDM, although further study is required to confirm this.

Original languageEnglish (US)
JournalJournal of clinical gastroenterology
DOIs
StateAccepted/In press - 2020

Keywords

  • drug concentrations, ulcerative colitis, Crohn's disease
  • inflammatory bowel disease
  • therapeutic drug monitoring

ASJC Scopus subject areas

  • Gastroenterology

Fingerprint Dive into the research topics of 'Therapeutic drug monitoring for current and investigational inflammatory bowel disease treatments'. Together they form a unique fingerprint.

Cite this