What is Ocaliva (obeticholic acid) used for?

Ocaliva (Obeticholic Acid) Usage in Primary Biliary Cholangitis

Ocaliva (obeticholic acid) is primarily used for the treatment of adult patients with primary biliary cholangitis (PBC) without cirrhosis or with compensated cirrhosis who do not have evidence of portal hypertension, either in combination with ursodeoxycholic acid (UDCA) when there is an inadequate response to UDCA alone, or as monotherapy in patients unable to tolerate UDCA. 1

Mechanism and Indication

Obeticholic acid is a farnesoid X receptor (FXR) agonist that works by:

• Decreasing bile acid synthesis
• Reducing inflammation in the liver
• Decreasing fibrosis progression

The FDA approved Ocaliva under accelerated approval based on its ability to reduce alkaline phosphatase (ALP) levels, though an improvement in survival or disease-related symptoms has not yet been established in confirmatory trials. 1

Patient Selection Criteria

Ocaliva is specifically indicated for:

• PBC patients who have had an inadequate response to UDCA after 12 months of treatment at 13-15 mg/kg/day (defined as ALP ≥1.67 times ULN and/or total bilirubin >ULN) 2
• Patients who cannot tolerate UDCA therapy 1

Important Contraindications

Ocaliva is contraindicated in patients with:

• PBC with decompensated cirrhosis (Child-Pugh Class B or C)
• Prior decompensation events
• Compensated cirrhosis with evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia)
• Complete biliary obstruction 1

Dosing Protocol

The recommended dosing regimen is:

1. Start with 5 mg once daily for the first 3 months
2. After 3 months, if inadequate reduction in ALP and/or total bilirubin and the patient is tolerating Ocaliva, increase to a maximum dosage of 10 mg once daily 1

Safety Monitoring

Regular monitoring is essential during Ocaliva treatment:

• Monitor liver biochemistry (ALP, bilirubin, transaminases) every 3 months 2
• Closely monitor patients with compensated cirrhosis for new evidence of portal hypertension
• Watch for increases in total bilirubin, direct bilirubin, or prothrombin time
• Monitor for severe pruritus, which is a common side effect 1

Black Box Warning

The FDA has issued a boxed warning for Ocaliva due to reports of hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, in PBC patients with cirrhosis. This warning came after approximately 15 months post-approval when 19 deaths and 11 cases of serious liver injury were reported in patients taking obeticholic acid. 3

Management of Side Effects

Pruritus Management

For patients with intolerable pruritus:

1. Add an antihistamine or bile acid binding resin
2. Reduce the dosage to 5 mg every other day (if intolerant to 5 mg daily)
3. Temporarily interrupt Ocaliva dosing for up to 2 weeks if necessary
4. Consider discontinuation if persistent, intolerable pruritus despite management strategies 1

Monitoring for Hepatotoxicity

Permanently discontinue Ocaliva if:

• Laboratory or clinical evidence of hepatic decompensation develops
• Patients with compensated cirrhosis develop evidence of portal hypertension
• Clinically significant hepatic adverse reactions occur 1

Clinical Evidence of Efficacy

Recent studies have demonstrated that Ocaliva treatment leads to:

• Significant decrease in liver enzymes including AST, ALT, and GGT 4
• Reduction in liver stiffness measurements, suggesting improvement in fibrosis 4
• Positive trend in enzymatic liver function 4

Conclusion

Ocaliva represents an important second-line therapy for PBC patients who don't respond adequately to UDCA or cannot tolerate it. However, careful patient selection, appropriate dosing, and vigilant monitoring are essential to minimize the risk of serious adverse events, particularly hepatic decompensation in patients with advanced liver disease.