Etiology and Management of Lack or Loss of Response to Anti-Tumor Necrosis Factor Therapy in Patients With Inflammatory Bowel Disease

Fine S1, Papamichael K1, Cheifetz AS1. nGastroenterol Hepatol (N Y). 2019 Dec;15(12):656-665.


Author information

Dr Fine is director of the Center for Inflammatory Bowel Disease at Brown Medicine at the Warren Alpert Medical School of Brown University in Providence, Rhode Island. Dr Papamichael is a research fellow in the Division of Gastroenterology at Beth-Israel Deaconess Medical Center in Boston, Massachusetts. Dr Cheifetz is director of the Center for Inflammatory Bowel Diseases at Beth-Israel Deaconess Medical Center.


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.

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