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Journal Articles New England Journal of Medicine Year : 2018

A Placebo-controlled Trial of Bezafibrate in Primary Biliary Cholangitis

Olivier Chazouillères
  • Function : Author
Alexandra Rousseau
  • Function : Author
Antonia Le Gruyer
  • Function : Author
François Habersetzer
  • Function : Author
Philippe Mathurin
  • Function : Author
Odile Goria
  • Function : Author
Pascal Potier
  • Function : Author
Anne Minello
  • Function : Author
Christine Silvain
Armand Abergel
Maryline Debette-Gratien
  • Function : Author
Dominique Larrey
  • Function : Author
Olivier Roux
  • Function : Author
Jean-Pierre Bronowicki
  • Function : Author
Jérôme Boursier
  • Function : Author
Victor De Ledhingen
  • Function : Author
Alexandra Heurgue-Berlot
  • Function : Author
Eric Nguyen-Khac
Fabien Zoulim
Isabelle Ollivier-Hourmand
  • Function : Author
Jean-Pierre Zarski
  • Function : Author
Gisèle Nkontchou
  • Function : Author
Lydie Humbert
  • Function : Author
Dominique Rainteau
  • Function : Author
Guillaume Lefèvre
  • Function : Author
Luc De Chaisemartin
  • Function : Author
Sylvie Chollet-Martin
  • Function : Author
Farid Gaouar
  • Function : Author
Farid-Hakeem Admane
  • Function : Author
Tabassome Simon
  • Function : Author
Raoul Poupon
  • Function : Author

Abstract

BACKGROUND Patients with primary biliary cholangitis (PBC) who inadequately respond to ursodeoxycholic acid (UDCA) therapy are at high risk of disease progression. Fibrates, which are agonists of peroxisome proliferator-activated receptors, in combination with UDCA, have shown potential benefit in this condition. METHODS In this 24-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 100 patients who had an inadequate response to UDCA according to the Paris-2 criteria to receive bezafibrate, at a daily dose of 400 mg (n=50), or placebo (n=50), in addition to continued treatment with UDCA. The primary outcome was a complete biochemical response defined as normal levels at 24 months of all of the following: total bilirubin, alkaline phosphatase (ALP), aminotransferases, albumin, and prothrombin index. RESULTS The primary outcome occurred in 30% of patients with bezafibrate and 1% with placebo (difference [95%CI] = 29% [16% ; 43%]; P < 0.001). Normalization of ALP occurred in 67% of patients with bezafibrate and 2% with placebo. Changes in pruritus, fatigue, and non-invasive markers of liver fibrosis, including liver stiffness measurement and Enhanced Liver Fibrosis score, were consistent with the primary outcome. Two patients in each group experienced end-stage liver complications. Creatinine level increased 5% in the bezafibrate group and decreased 3% in the placebo group. Myalgia was experienced by 20% in bezafibrate and 10% in placebo group. CONCLUSIONS Bezafibrate administered with UDCA in patients with PBC who had inadequate response to UDCA alone resulted in a significantly higher rate of complete biochemical response than placebo with UDCA. (Funded by the Assistance Publique–Hôpitaux de Paris with support from Arrow Génériques; BEZURSO ClinicalTrials.gov number, NCT01654731).
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Dates and versions

hal-03972495 , version 1 (03-02-2023)

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  • HAL Id : hal-03972495 , version 1

Cite

Christophe Corpechot, Olivier Chazouillères, Alexandra Rousseau, Antonia Le Gruyer, François Habersetzer, et al.. A Placebo-controlled Trial of Bezafibrate in Primary Biliary Cholangitis. New England Journal of Medicine, 2018. ⟨hal-03972495⟩
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