Assays predict non-response to anti-TNF-alpha therapy in IBD

Last Updated: 2018-04-19

By Will Boggs MD

NEW YORK (Reuters Health) - Two assays, one biopsy-based and one blood-based, can predict non-response to anti-TNF-alpha therapy prior to starting treatment in patients with inflammatory bowel disease (IBD), according to findings of the Israeli IBD Research Network.

"The discovery of a novel anti-TNF non-responder dominant inflammatory pathway is of major importance for both understanding the pathophysiology of this condition and for developing novel therapeutics based on such understanding," Dr. Yehuda Chowers from Rambam Health Care Campus, in Haifa, told Reuters Health by email.

IBD remission rates with anti-TNF-alpha therapy are only 10% to 20% in real-life cohorts, and 13% to 24% of patients commonly lose responsiveness within 12 months.

Dr. Chowers and colleagues used sophisticated statistical approaches to identify biomarkers in colon biopsies and peripheral blood to predict anti-TNF-alpha non-response in patients with IBD and then validated these markers in "real-life" cohorts.

Pretreatment plasma cell proportions in colon biopsies were significantly higher among patients who later did not respond to anti-TNF-alpha treatment, the team reports in Gut, online April 4.

Elevated plasma cell frequency in such biopsies predicted non-response to anti-TNF-alpha treatment with accuracies ranging from 71% overall to 84% when restricted to highly inflamed tissues.

In baseline blood samples, triggering receptor expressed on myeloid cells 1 (TREM-1) was more highly overexpressed among non-responders and proved 94% accurate for predicting non-response to anti-TNF-alpha treatment.

TREM-1 promotes inflammation by driving production of inflammatory cytokines, including interleukin 8 and TNF-alpha.

"Once relevant cut-off values are determined, such measurements will allow to personalize treatment, prevent unnecessary tissue damage and expenditures," the researchers conclude.

"The main clinical takeaway message is that drug treatment can be personalized based on deep analysis of physiological processes, leading to much more focused, efficacious, and cost-effective personalized treatment approaches," Dr. Chowers said. "Although validated in a number of retrospective cohorts, the findings will have to be substantiated in prospective cohorts before actual clinical application."

SOURCE: https://bit.ly/2vqZwvU

Gut 2018.