Intestinal fibrosis in IBD hard to diagnose, treat

By Reuters Staff

NEW YORK (Reuters Health) - 19/7/2019

Intestinal fibrosis in patients with inflammatory bowel disease (IBD) is challenging to diagnose, and there are no approved antifibrotic therapies, according to a meeting summary.

Intestinal fibrosis, a common complication of IBD, is usually the consequence of chronic inflammation. Currently available anti-inflammatory therapies have had little impact on intestinal fibrosis.

Dr. Geert D'Haens from Amsterdam University Medical Center and colleagues in the International Organization for IBD participated in a workshop in December 2018. The aim was to review the current knowledge of the biological background, diagnosis and treatment of intestinal fibrosis, as well as to discuss potential clinical trial endpoints.

The main drivers of mesenchymal-cell activation and differentiation that ultimately result in fibrosis appear to be luminal microorganisms and bacterial products, along with growth factors and cytokines released from immune and non-immune cells, the team note in a report from the workshop, online June 26 in Gastroenterology.

Several potential biomarkers have been identified, the authors say, including at least two genes (NOD2 and MMP-3) and several serologic parameters associated with the development of IBD and, in some cases, with fibrosis.

MRI, CT, and intestinal ultrasound have all been used to differentiate fibrosis and inflammation in patients with IBD, but it remains to be seen which outcome measure will prove to be robust in clinical and research settings.

Although no antifibrotic therapies have demonstrated effectiveness, promising candidates include an antibody to the IL-36 receptor, inhibitors of/antibodies against TNF-like cytokine 1A (TL1A), and any of a host of agents approved or under investigation for fibrosis in other organs.

In their discussions of trial design, the authors reached consensus on MRI being the preferred imaging technique to define strictures and assess response to therapy and on 24-48 weeks of therapy as an appropriate duration for pharmacologic trials.

"Although intestinal fibrosis is a complex and challenging disorder, numerous preclinical and clinical efforts have resulted in promising advances," they conclude.

Several drug companies supported the meeting, and most of the authors report ties to one or more of these companies.

Dr. D'Haens did not respond to a request for comments.


Gastroenterol 2019.

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