23 Oct Bile Acid Diarrhea May Be Helped By New Drug Class

MedicalResearch.com Interview Invitation
Julian Walters
Professor of Gastroenterology
Section of Hepatology & Gastroenterology | Imperial College London
Consultant Gastroenterologist
Imperial College Healthcare Hammersmith Hospital
London W12 0HS | UK

Medical Research: What is the background for this study?  What is Bile acid diarrhoea (BAD)?

Dr. Walters: Bile acid diarrhoea accounts for about a third of the patients who would otherwise be diagnosed as IBS-D (irritable bowel syndrome – diarrhoea predominant).  We estimate about 1% of the adult population have this primary disorder; others may have it secondary to previous surgery such as ileal resection in Crohn’s disease or post-cholecystectomy.  There are unmet needs to improve diagnosis rates and to improve the current treatment with bile acid sequestrants which can be poorly tolerated and do not address the primary pathology.  We have shown that primary BAD patients have reduced levels of Fibroblast Growth Factor 19 (FGF19) the ileal hormone that regulates bile acid synthesis.

Medical Research: What are the main findings of the study?

Dr. Walters: Obeticholic acid is the first in class farnesoid X receptor (FXR) agonist drug.  We have shown that this will increase FGF19 levels in the primary BAD patients with the consequence of reducing excessive bile acid production.  Obeticholic acid treatment produced symptomatic benefits improving stool frequency and stool type, particularly in all the primary BAD patients and in those with secondary BAD who did not have long ileal resections.

Medical Research: What should clinicians and patients take away from your report?

Dr. Walters: This study confirms the concept that FGF19 is central to the pathology of Bile Acid Diarrhoea and shows that a drug which produces improvements in FGF19 levels helps to treat the disease.  Although these agents will be a long time reaching general clinical use, this study identifies a new pathway for drug development.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Walters: Larger randomised, double-blind prospective studies will be needed to confirm the benefits of obeticholic acid and to compare its cost-effectiveness with other treatments.  Focusing further research on the FXR-FGF19 pathway will help to understand this disorder.

Citation:
Julian R. F. Walters, I. M. Johnston, J. D. Nolan, C. Vassie, M. E. Pruzanski, D. A. Shapiro. The response of patients with bile acid diarrhoea to the farnesoid X receptor agonist obeticholic acid. Alimentary Pharmacology & Therapeutics, 2014; DOI: 10.1111/apt.12999

Last Updated on October 24, 2014 by Marie Benz MD FAAD