Pharmacologic management of primary sclerosing cholangitis: what’s in the pipeline?

ABSTRACT

Introduction: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by biliary inflammation, fibrosis, and stricturing. Although considered progressive, its course is difficult to predict, and there is currently no definitive therapy shown to alter disease course and prevent death or the need for liver transplantation.

Areas covered: There are multiple agents in the pipeline targeting various pathways hypothesized to lead to and drive this disease. Some are already used for other treatment indications, including antibiotics such as oral vancomycin, metronidazole, and minocycline. Other agents including obeticholic acid, nor-ursodeoxycholic acid, and monoclonal antibodies are also under investigation. This narrative review focuses on the most recent published clinical trials available for discussion. We attempt to summarize the data on current and future treatment options.

Expert opinion: The rarity of this condition and poor understanding of its pathophysiology have created a void for safe and effective treatment options to alter mortality or transplant free survival. Nevertheless, some agents currently being tested have demonstrated therapeutic potential. We await validation and prospective data on these agents in hopes of modifying the disease course for patients in the future.

KEYWORDS:

• Primary sclerosing cholangitis
• management
• ursodeoxycholic acid
• antibiotics
• obeticholic acid
• primary biliary cholangitis
• cholestatic liver disease

Article Highlights

• Primary sclerosing cholangitis is an uncommon disease with an incompletely understood pathophysiology and a significant impact on patient outcomes.

• Currently, no pharmacotherapy has shown to reliably reduce mortality or the need for liver transplantation.

• The pharmacologic agent most widely used is ursodeoxycholic acid, but currently it is not universally accepted as standard of care by leading organizations in liver disease. There is extensive debate regarding its utility.

• Drugs such as obeticholic acid, vancomycin, metronidazole, and nor-ursodeoxycholic acid have emerged as possible therapeutic options in the future with ongoing trials filling the need for long term results in larger sample populations.

• Presently, health providers remain restricted as to what they can safely offer that has proven efficacy.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.