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

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 BureauRodolphe Anty, Dominique Larrey, Cynthia Levy, Albert Pares, Christoph Schramm, Frederik Nevens, Olivier Chazouillères, Christophe Corpechot

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1138-1146
Number of pages9
JournalAlimentary Pharmacology and Therapeutics
Volume53
Issue number10
DOIs
StatePublished - May 2021

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult-to-treat primary biliary cholangitis'. Together they form a unique fingerprint.

Cite this