The management of patients with moderate to severe inflammatory bowel disease was transformed with the arrival of anti-tumor necrosis factor (TNF) therapy. Nevertheless, a considerable number of patients do not respond to anti-TNF induction therapy (primary nonresponse) or lose response to treatment over time after initially experiencing clinical improvement (secondary loss of response). Studies suggest that these outcomes are often due to inadequate drug concentrations. Therapeutic drug monitoring (TDM) is a practical tool that can be used to better define the etiologies of and help manage primary nonresponse or secondary loss of response. Proactive TDM, or drug titration to a target trough concentration, can improve the efficacy of anti-TNF treatment and lead to favorable clinical outcomes. However, in patients with adequate anti-TNF drug concentrations and active disease, alternate pathways of inflammation (not driven by TNFa agents) are at play, and therapies with another mechanism of action should be employed.
Keywords: Primary nonresponse; antidrug antibody; secondary loss of response; therapeutic drug monitoring.
Copyright © 2019, Gastro-Hep Communications, Inc.
Conflict of interest statement
Dr Cheifetz has received consultancy fees from Janssen, AbbVie, Takeda, Pfizer, Samsung, Arena Pharmaceuticals, Bacainn Therapeutics, EMD Serono, Arsanis, Grifols, and Prometheus, and has received research support from Inform Diagnostics. Dr Fine is on the speaking bureau for AbbVie. Dr Papamichael has received a lecture fee from Mitsubishi Tanabe Pharma.
Therapeutic Drug Monitoring During Induction of Anti-Tumor Necrosis Factor Therapy in Inflammatory Bowel Disease: Defining a Therapeutic Drug WindowK Papamichael et al. Inflamm Bowel Dis 23 (9), 1510-1515. PMID 28816757. - ReviewAnti-tumor necrosis factor (TNF) therapy has revolutionized the treatment of inflammatory bowel disease (IBD). However, up to 30% of patients with IBD show no clinical be …
Use of anti-TNF Drug Levels to Optimise Patient ManagementK Papamichael et al. Frontline Gastroenterol 7 (4), 289-300. PMID 28839870. - ReviewAnti-tumour necrosis factor (TNF) therapies, such as infliximab, adalimumab, certolizumab pegol and golimumab, have been proven to be effective for the treatment of patie …
Role for Therapeutic Drug Monitoring During Induction Therapy With TNF Antagonists in IBD: Evolution in the Definition and Management of Primary NonresponseK Papamichael et al. Inflamm Bowel Dis 21 (1), 182-97. PMID 25222660.: Primary nonresponse and primary nonremission are important limitations of tumor necrosis factor (TNF) antagonists, occurring in 10% to 40% and 50% to 80% of patients wi …
Therapeutic Drug Monitoring of anti-TNF Therapy in Children With Inflammatory Bowel DiseaseK van Hoeve et al. Expert Opin Drug Saf 17 (2), 185-196. PMID 29202588. - ReviewAlthough TDM is not yet widely used in pediatric IBD, the available literature suggests it to be a promising tool, especially in patients with LOR to anti-TNF. There is i …
Therapeutic Drug Monitoring in Children and Young Adults With Inflammatory Bowel Disease: A Practical ApproachN Singh et al. Gastroenterol Hepatol (N Y) 11 (1), 48-55. PMID 27099572.Therapeutic drug monitoring (TDM) is the clinical practice of measuring drug concentrations or metabolites to attain a targeted concentration in a patient's bloodstream, …