Author information

• ¹UPMC Children's Hospital of Pittsburgh, Department of Pediatrics, 4401 Penn Ave, Pittsburgh PA 15224, USA.
• ²UPMC Children's Hospital of Pittsburgh, Department of Pharmacy, 4401 Penn Ave, Pittsburgh PA 15224, USA.
• ³UPMC Children's Hospital of Pittsburgh, Division of Gastroenterology and Hepatology, 4401 Penn Ave, Pittsburgh PA 15224, USA.

Abstract

Introduction: Progressive familial intrahepatic cholestasis (PFIC) refers to a group of heterogeneous mostly autosomal recessive disorders resulting from the inability to properly form and excrete bile from hepatocytes. The resulting shared phenotype is one of hepatocellular cholestasis. Clinical management targeting refractory itch and surgical interventions to interrupt the enterohepatic circulation are often pursued with variable efficacy. Recent development of the family of medications referred to as the IBAT inhibitors has introduced a novel tool in the armamentarium for the treatment of PFIC.

Areas covered: Data from Phase 3 and 3 clinical trials were reviewed. The primary endpoints in most studies included effect on pruritus, serum bile acid levels, and quality of life metrics, with the duration of the study ranging between 24-72 weeks. Most common adverse events included diarrhea, vomiting and elevation in transaminases.

Expert opinion: IBAT inhibition with therapeutics such as odevibixat have shown that it is well-tolerated and efficacious in mitigating itch and reducing serum bile acid levels. While the few early published trials with odevixibat have shown good efficacy, what remains to be seen is long-term, sustainable improvement and if or how these medications will supplement or replace the current medical and surgical therapies available for managing PFIC disorders.