Ileal Bile Acid Transporter Inhibitors in Cholestasis: Potential for More Than Just Paediatrics?

Ileal bile acid transporter inhibitors (IBATi) are a new, attractive therapeutic mechanism to alter the enterohepatic circulation through depletion of the bile acid pool by blocking bile acid reuptake in the ileum leading to improvements in pruritus and liver function in cholestatic liver diseases. These drugs may also have an impact on immunity, the gut microbiome, and motility. IBATi are approved in Japan for the treatment of idiopathic chronic constipation. There are two IBATi, maralixibat and odevixibat, that have been extensively investigated in clinical trials and are FDA approved for cholestatic pruritus in progressive familial intrahepatic cholestasis and Alagille syndrome. Clinical trials exploring IBATi in other cholestatic conditions, such as biliary atresia, primary biliary cholangitis, and primary sclerosing cholangitis, are currently ongoing. In this review, we will outline the emerging data regarding the physiology and mechanism of action for the IBATi class, an overview of clinical trials that led to the approval of maralixibat and odevixibat, ongoing clinical trials in adult cholestatic liver diseases, and the future of this drug class in systemic apical sodium bile acid transporter inhibitors.

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