What is the difference between obeticholic acid and ursodeoxycholic acid?

Obeticholic acid (Obeticholic acid) and ursodeoxycholic acid (UDCA) are two drugs used to treat primary biliary cholangitis (PBC), but they have obvious differences in mechanisms, indications and clinical applications.

First, obeticholic acid is a selective farnesoid X receptor (FXR) agonist that received accelerated approval in 2016 for use in patients with PBC who have had poor response to ursodeoxycholic acid or as monotherapy in adults who cannot tolerate UDCA. In contrast, ursodeoxycholic acid is widely used in a variety of diseases, including PBC, gallbladder disease, and non-alcoholic steatohepatitis. Both drugs may be used for other purposes not listed in the guidelines, but their primary indications differ.

Primary cholangitis is an autoimmune disease characterized by destruction of bile ducts in the liver, leading to cholestasis and inflammation, which in turn affects liver function and is usually manifested by elevated serum alkaline phosphatase concentrations. This damage can lead to cirrhosis of the liver, which is why it is also called primary biliary cirrhosis. In this context, the therapeutic goal of ursodeoxycholic acid is to improve patient outcomes by slowing disease progression and delaying the need for liver transplantation. Studies have shown that ursodeoxycholic acid can promote bile flow and reduce the effects of cholestasis, and it does not inhibit bile acid synthesis. In comparison, obeticholic acid effectively reduces the concentration of bile acids in the liver by activating FXR, thereby reducing inflammation and fibrosis, showing a better therapeutic effect.

In terms of efficacy, clinical trial results show that obeticholic acid shows good tolerability and substantial improvement in improving liver biochemical indicators related to cholestasis. For example, OCA has shown the ability to significantly reduce alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the immunological parameter C-reactive protein (CRP) in trials of PBC patients. Improvement in these indicators means protection of liver function and delay in disease progression.

Research on combination treatments has also yielded some interesting findings. For patients who have a poor response to or intolerance to ursodeoxycholic acid, adding obeticholic acid to treatment is a reasonable option. Although most patients experience a decrease in alkaline phosphatase concentrations after OCA use, the clinical consequences are unclear. In a double-blind phase III trial, there was no significant difference in liver fibrosis between OCA and placebo, and the 10-year predicted risk of death or liver transplantation decreased only slightly, from 20% at baseline to 18.95% at 48 months.

Meta-analysis shows that There is no significant difference between combined treatment of UDCA and OCA and UDCA monotherapy in improving the primary endpoint, but combined treatment is significantly better than monotherapy in reducing liver biochemical indicators and some immunological parameters. This provides new ideas and evidence base for rational combination therapy for patients with refractory PBC.

Reference materials:https://www.drugs.com/compare/obeticholic-acid-vs-ursodiol