What are the treatment options for Primary Biliary Cholangitis (PBC)?

From the Guidelines

The primary treatment for Primary Biliary Cholangitis (PBC) is ursodeoxycholic acid (UDCA), typically prescribed at a dose of 13-15 mg/kg/day, taken orally in divided doses, as recommended by the most recent guidelines 1. This medication should be continued indefinitely as it slows disease progression and improves liver biochemistry. The use of UDCA has been consistently supported by various studies, including those published in the Journal of Hepatology 1, and more recently, the British Society of Gastroenterology/UK-PBC guidelines 1.

Key Considerations

• For patients who don't respond adequately to UDCA after 12 months, obeticholic acid (Ocaliva) at 5-10 mg daily is recommended as second-line therapy, as suggested by recent clinical practice guidelines 1.
• Symptom management is also important: cholestyramine (4-16 g/day) can help with itching, while fat-soluble vitamin supplements (A, D, E, K) may be necessary due to fat malabsorption.
• For advanced disease with liver failure, liver transplantation becomes the definitive treatment option.
• Regular monitoring of liver function tests every 3-6 months is essential to assess treatment response.

Mechanism and Rationale

UDCA works by protecting bile duct cells from toxic bile acids, reducing inflammation and fibrosis, while obeticholic acid activates farnesoid X receptors to decrease bile acid production and inflammation. Early treatment is crucial as it can significantly delay progression to cirrhosis and liver failure in this autoimmune disease that primarily affects the bile ducts, as highlighted in the EASL clinical practice guidelines 1.

Clinical Guidelines and Recommendations

The British Society of Gastroenterology/UK-PBC guidelines 1 and the EASL clinical practice guidelines 1 provide a comprehensive framework for the management of PBC, emphasizing the importance of UDCA as the first-line treatment and the need for regular monitoring and assessment of treatment response.

From the FDA Drug Label

OCALIVA® is indicated 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) with an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA. The recommended dosage of OCALIVA for PBC patients without cirrhosis or with compensated cirrhosis who do not have evidence of portal hypertension, who have not achieved an adequate biochemical response to an appropriate dosage of UDCA for at least 1 year or are intolerant to UDCA follows below: Start with a dosage of 5 mg once daily for the first 3 months. After the first 3 months, for patients who have not achieved an adequate reduction in ALP and/or total bilirubin and who are tolerating OCALIVA, increase to a maximum dosage of 10 mg once daily.

Treatment for PBC: Obeticholic acid (OCALIVA) is indicated 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.

• The recommended starting dosage is 5 mg once daily for the first 3 months, which can be increased to a maximum dosage of 10 mg once daily if the patient has not achieved an adequate reduction in ALP and/or total bilirubin and is tolerating the treatment.
• OCALIVA can be used in combination with ursodeoxycholic acid (UDCA) in patients with an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA 2, 2.

From the Research

Treatment Options for Primary Biliary Cholangitis (PBC)

• First-line treatment for PBC is ursodeoxycholic acid (UDCA), which improves cholestatic surrogate markers and is associated with a favorable survival free of liver transplantation, even in cases of incomplete biochemical response 3.
• Despite adequate UDCA therapy, patients remain at risk of liver disease progression, and on-treatment multifactor-based risk stratification is necessary to identify patients in need of additional therapy 3, 4.
• Second-line treatment options for patients with inadequate response to UDCA include obeticholic acid (OCA), fibrates (such as bezafibrate), and corticosteroids (such as budesonide) 4, 5, 6.
• OCA has been shown to improve surrogate markers of prognosis in PBC and is licensed for use as a second-line treatment 4, 7.
• Fibrates have also been shown to improve surrogate endpoints and clinical outcome in patients with PBC, although more robust studies are needed to confirm these results 6.
• Triple therapy with UDCA, OCA, and bezafibrate may be considered in patients showing inadequate response to dual therapy 4.

Patient Evaluation and Management

• Patients with PBC should be evaluated at baseline and on-treatment for the risk of progressive disease and eventually treated with second-line therapies in addition to UDCA 4, 5.
• Markers of response to therapy include reduced serum levels of alkaline phosphatase and bilirubin, and patients with high levels of total and conjugated bilirubin or levels of alkaline phosphatase more than 1.5-fold the upper limit of normal should be considered for second-line therapy 5.
• Patients with adequate biochemical responses can continue UDCA monotherapy, while incomplete responders should be considered for second-line therapies 5.
• Patients with PBC should be followed up for life to monitor disease progression and adjust treatment as needed 5.