Primary Biliary Cholangitis is an autoimmune chronic liver disease formerly known as biliary cirrhosis. This disease results in destruction of bile ducts in the liver, which builds up bile and other toxins in the liver and causes inflammation and scarring. Eventually, if left untreated, it can severely damage the liver and their functions become impaired. Since this disease is chronic with no cure yet, medications are given to help slow the progression of this disease and prevent complications. The most common medicine used by the doctors for this disease is Ursodeoxycholic Acid (UDCA) which helps to move bile from the liver. Another medicine that has shown promising results is the use of Obeticholic Acid in patients with primary biliary cholangitis. It was approved by the US Food and Drug Administration in adult patients when they had a negative response to UDCA treatments.
A study was conducted in order to test the safety and effectiveness of Obeticholic Acid in patients with primary biliary cholangitis. It was a 12 months, double-blind, placebo-controlled phase 3 trial, where 217 patients who had an inadequate response to ursodil or who found the side-effects of ursodiol unacceptable were chosen.They were given obeticholic acid at a dose of 10 mg (the 10-mg group), obeticholic acid at a dose of 5 mg with adjustment to 10 mg if applicable (the 5–10-mg group), or placebo. The primary endpoint was an alkaline phosphatase level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% from baseline, and a normal total bilirubin level. The results of this study : In patients with primary biliary cholangitis, obeticholic acid treated with ursodiol or as monotherapy for 12 months resulted in decreases in baseline levels of alkaline phosphatase and total bilirubin that varied significantly from the changes observed with placebo. Obeticholic acid has had more extreme adverse incidents.
Both synthetic bile acids are UDCA and obeticholic acid, and have complementary mechanisms of action. Obeticholic acid is a stimulant of the Farnesoid X receptor (FXR) that is active in a large range of pathways. It reduces the synthesis of bile acids, leading to less accumulation of toxic bile acids and less cholestatic damage. It also increases the secretion of bile acid at the same time. Choleretic effects include both obeticholic acid and UDCA, causing more bile acid flow, less accumulation of harmful bile acids in the parenchyma of the liver, as well as less inflammation and direct cell damage. Obeticholic acid has the primary side effect of pruritus. The remaining side effects are mild, normal symptoms that can occur for a year (e.g., tiredness, abdominal pain, rash, dizziness, constipation) and may or may not be associated with the medication.
