Emerging drugs for the treatment of Primary Biliary Cholangitis

ABSTRACT

Introduction: Primary biliary cholangitis (PBC) is an autoimmune chronic disease of the liver that can progress to cirrhosis and hepatocellular carcinoma. It affects approximately 1 in 4,000 with a 10:1 female to male ratio. The diagnosis of PBC can be made based on serum antimitochondrial antibodies (AMA) in a patient with abnormally high serum alkaline phosphatase after ruling out other causes of cholestasis and biliary obstruction. Genome-wide association studies have revealed several human leukocyte antigen (HLA) and non-HLA risk loci in PBC, and complex environmental-host immunogenetic interactions are believed to underlie the etiopathogenesis of the disease. Fatigue and pruritus are the most common and often problematic symptoms; although often mild, these can be severe and life-alternating in a subset of patients. Ursodeoxycholic acid (UDCA) is the only drug approved by the United States Food and Drug Administration for the treatment of PBC. Clinical trials have shown that UDCA significantly improves transplant-free survival. However, nearly 40% of PBC patients do not respond adequately to PBC and are at higher risk for serious complications when compared to PBC patients with complete response to UDCA.

Areas Covered: Here we provide a detailed discussion regarding novel therapeutic agents and potential areas for further investigation in PBC-related research.

Expert Opinion: Results of ongoing clinical trials and emerging treatment paradigms for PBC will likely further improve medical management of this disorder in the near future.

KEY WORDS:

• Primary biliary cholangitis
• ursodeoxycholic acid
• transplantation
• cholestasis
• bile duct disorders
• pharmacotherapy
• outcomes

Declaration of Interest

K Lindor serves as an unpaid advisor to Intercept Pharmaceuticals and Lumena Pharmaceutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.