Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult-to-treat primary biliary cholangitis.

Abstract

BACKGROUND:

Obeticholic acid (OCA) and fibrates are second-line therapies for patients with primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA).

AIM:

To know whether OCA and fibrates, administered together in combination with UDCA, have additive beneficial effects in patients with difficult-to-treat PBC.

METHODS:

PBC patients treated for ≥3 months with UDCA, OCA and fibrates (bezafibrate or fenofibrate) due to failure of either second-line therapy were included in a multicentre, uncontrolled retrospective cohort study. Changes in biochemical liver tests and pruritus were analysed using a generalised linear mixed-effect model.

RESULTS:

Among 58 patients included, half received OCA as second-line and fibrates as third-line therapy (Group OCA-Fibrate), while the other half had the inverse therapeutic sequence (Group Fibrate-OCA). The mean duration of triple therapy was 11 months (range 3-26). Compared to dual therapy, triple therapy was associated with a significant gain in alkaline phosphatase (ALP) reduction: 22% per first year (95% CI 12%-31%), an effect that was stronger in OCA-Fibrate than in Fibrate-OCA group. Triple therapy was associated with a 3.4 (95% CI 1.4-8.2) odds ratio (OR) of reaching normal ALP and with a significant decrease in gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. The ORs of achieving the Paris-2 and Toronto criteria of adequate biochemical response were 6.8 (95% CI 2.8-16.7) and 9.2 (95% CI 3.4-25.1) respectively. Finally, triple therapy significantly improved pruritus in OCA-Fibrate but not in Fibrate-OCA group.

CONCLUSIONS:

Triple therapy with UDCA, OCA and fibrates is able to normalise biochemical liver tests and improve pruritus in patients with difficult-to-treat PBC.

• Authors: Pierre-Antoine Soret, Laurent Lam, Fabrice Carrat, Lena Smets, Thomas Berg, Marco Carbone, Pietro Invernizzi, Vincent Leroy, Palak Trivedi, Nora Cazzagon, Christina Weiler-Normann, Laurent Alric, Isabelle Rosa-Hezode, Alexandra Heurgué, Jean-Paul Cervoni, Jérôme Dumortier, Pascal Potier, Olivier Roux, Christine Silvain, Christophe Bureau, Rodolphe Anty, Dominique Larrey, Cynthia Levy, Albert Pares, Christoph Schramm, Frederik Nevens, Olivier Chazouillères, Christophe Corpechot
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 53 Issue 10 Pg. 1138-1146 (05 2021) ISSN: 1365-2036 [Electronic] England
• PMID: 33764590 (Publication Type: Journal Article)
• Copyright: © 2021 John Wiley & Sons Ltd.

Chemical References

• Cholagogues and Choleretics
• Fibric Acids
• obeticholic acid
• Chenodeoxycholic Acid
• Ursodeoxycholic Acid

Topics

• Chenodeoxycholic Acid (analogs & derivatives)
• Cholagogues and Choleretics (therapeutic use)
• Fibric Acids (therapeutic use)
• Humans
• Liver Cirrhosis, Biliary (drug therapy)
• Retrospective Studies
• Ursodeoxycholic Acid (therapeutic use)