The FDA has issued a safety alert concerning severe liver injury in patients with primary biliary cholangitis (PBC) treated with obeticholic acid (Ocaliva; Intercept Pharmaceuticals) who do not have cirrhosis. This followed the observation in a clinical trial that such patients had a higher risk of having a need for a liver transplant and risk of death than those taking the placebo.

Key Highlights 

1. Background on Obeticholic Acid: Obeticholic acid received FDA approval in May 2016 for PBC patients who do not respond well to ursodeoxycholic acid, based on improvements in alkaline phosphatase (ALP) levels.  The FDA limited its use in PBC patients with advanced cirrhosis in May 2021 due to a higher risk of serious liver injury. 

   
   

2. Post-Market Clinical Trial Findings: The trial saw a higher number of liver transplants and deaths in the obeticholic acid arm among non-cirrhotic patients (7 out of 81) compared to those receiving placebo (1 out of 68). Hazard ratio for liver transplant or death in non-cirrhotic patients is 4.77 (95% CI: 1.03, 22.09).

   
   

3. Adverse Event Statistics: Between May 2021 and September 2024, there were 20 cases of serious liver-related adverse events reported globally, including 13 in the country.

   Events included liver transplants (7), evaluation or listing for liver transplant (8), and liver-related deaths (6).

   
   

4. Updated Recommendations from FDA: Healthcare professionals should monitor liver function tests frequently in patients on obeticholic acid.
   Obeticholic acid should be discontinued immediately upon signs of liver injury or worsening liver function.

   
   

5. Patient Education: The FDA encourages healthcare providers to educate PBC patients about signs and symptoms of liver injury, including:
   Swollen belly, yellow eyes or skin, black or bloody stool, vomiting blood, confusion, and changes in mood.
   Patients should also tell their doctors about symptoms like ongoing belly pain, feeling sick, tiredness, fever, or less urination.

   
   

6. Call to Action: Patients should talk openly with healthcare professionals about the risks and benefits of staying on obeticholic acid therapy.The latest findings by the FDA have highlighted the need for regular liver checks and patient education to avoid serious problems. Healthcare providers should remain alert and follow updated guidelines to keep patients safe while treating PBC with obeticholic acid.