What is the management of pruritus in Primary Biliary Cholangitis (PBC)?

From the Guidelines

For managing itch in primary biliary cholangitis (PBC), bezafibrate is recommended as the first-line pharmacological treatment, given its clear-cut benefit in alleviating moderate to severe itch in people with PSC and PBC treated with UDCA, as shown in the FITCH trial 1.

Treatment Approach

The treatment approach for PBC itch should prioritize bezafibrate due to its efficacy and safety profile.

• Bezafibrate can be used in combination with UDCA, which is the primary treatment for PBC at a dose of 13-15mg/kg/day, and may improve itch by improving bile flow 1.
• If bezafibrate is not effective or tolerated, rifampicin 150-300mg twice daily can be considered as a second-line treatment, with regular monitoring of liver function tests due to potential hepatotoxicity 1.
• Non-pharmacological approaches, such as using mild soaps, moisturizing regularly, avoiding hot baths, wearing loose cotton clothing, and keeping nails short, can also provide symptomatic relief.

Rationale

The rationale for using bezafibrate as the first-line treatment is based on the results of the FITCH trial, which demonstrated its efficacy in alleviating moderate to severe itch in people with PSC and PBC treated with UDCA 1.

• The trial showed that bezafibrate had a sustained antipruritic effect under cholestatic conditions, with no major side effects observed during short-term treatment.
• In contrast, rifampicin, which was previously considered a first-line treatment, may induce drug-induced hepatitis after 4-12 weeks in up to 12% of cholestatic patients 1.

Additional Considerations

Additional considerations for managing PBC itch include:

• Using emollients to prevent dryness of skin, avoiding hot baths or showers, and using cooling gels for affected skin areas 1.
• Considering novel medical antipruritic strategies, such as non-absorbable inhibitors of the ileal apical sodium bile salt transporter (ASBT) and selective PPARα or PPARδ agonists, although their effectiveness and tolerability are still being evaluated 1.

From the Research

Management of PBC Itch

• Pruritus is a common symptom in patients with primary biliary cholangitis (PBC) 2, 3
• Ursodeoxycholic acid (UDCA) is the first-line treatment for PBC, but some patients may experience inadequate response or intolerance 4, 3
• Obeticholic acid (OCA) is a second-line therapy that can improve surrogate markers of prognosis in PBC, but it can also cause pruritus as an adverse event 2, 3
• Bezafibrate is another option for patients with inadequate response to UDCA, as it can improve surrogate endpoints, pruritus, and clinical outcome 2
• Budesonide may be considered in patients with marked portal inflammation 2
• Triple therapy with UDCA, OCA, and bezafibrate may be considered in patients showing inadequate response to dual therapy 2

Treatment Targets for PBC

• New therapeutic targets for PBC are being identified, including modification of bile, inflammation, cell survival, or fibrosis 5
• Nuclear hormone receptors, such as farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR), regulate many of these pathways and are being pursued as potential therapeutic targets in PBC 5
• Stem cell therapy and lymphocyte trafficking inhibition are novel methods of broad immune regulation being explored for PBC treatment 5

Clinical Practice Implications

• 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 2, 3
• Risk stratification tools are well established, but some issues, such as bile acid dosage in routine practice, remain controversial 6
• Personalized approaches to PBC management may be facilitated by liver biopsy and risk stratification 6