Etiology and Management of Lack or Loss of Response to Anti-Tumor Necrosis Factor Therapy in Patients With Inflammatory Bowel Disease
- PMID: 31892912
- PMCID: PMC6935028
Etiology and Management of Lack or Loss of Response to Anti-Tumor Necrosis Factor Therapy in Patients With Inflammatory Bowel Disease
Abstract
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.
References
-
- Kornbluth A. Infliximab approved for use in Crohn’s disease: a report on the FDA GI Advisory Committee conference. Inflamm Bowel Dis. 1998;4(4):328–329. - PubMed
-
- Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD. ACG Clinical Guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019;114(3):384–413. - PubMed
-
- Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. ACG Clinical Guideline: management of Crohn’s disease in adults. Am J Gastroenterol. 2018;113(4):481–517. - PubMed
-
- Ben-Horin S, Kopylov U, Chowers Y. Optimizing anti-TNF treatments in inflammatory bowel disease. Autoimmun Rev. 2014;13(1):24–30. - PubMed
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources