Title :

A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis.

Author(s) :

Corpechot, Christophe [Auteur]
Chazouilleres, Olivier [Auteur]
Rousseau, Alexandra [Auteur]
Le Gruyer, Antonia [Auteur]
Habersetzer, Francois [Auteur]
Mathurin, Philippe [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Goria, Odile [Auteur]
Potier, Pascal [Auteur]
Minello, Anne [Auteur]
Silvain, Christine [Auteur]
Abergel, Armand [Auteur]
Debette-Gratien, Maryline [Auteur]
Larrey, Dominique [Auteur]
Roux, Olivier [Auteur]
Bronowicki, Jean-Pierre [Auteur]
Boursier, Jerome [Auteur]
De Ledinghen, Victor [Auteur]
Heurgue-Berlot, Alexandra [Auteur]
Nguyen-Khac, Eric [Auteur]
Zoulim, Fabien [Auteur]
Ollivier-Hourmand, Isabelle [Auteur]
Zarski, Jean-Pierre [Auteur]
N'kontchou, Gisele [Auteur]
Lemoinne, Sara [Auteur]
Humbert, Lydie [Auteur]
Rainteau, Dominique [Auteur]
Lefevre, Guillaume [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
De Chaisemartin, Luc [Auteur]
Chollet-Martin, Sylvie [Auteur]
Gaouar, Farid [Auteur]
Admane, Farid-Hakeem [Auteur]
Simon, Tabassome [Auteur]
Poupon, Raoul [Auteur]

Journal title :

The New England journal of medicine

Abbreviated title :

N. Engl. J. Med.

Volume number :

378

Pages :

2171-2181

Publication date :

2018-06-07

ISSN :

1533-4406

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Background Patients with primary biliary cholangitis who have an inadequate response to therapy with ursodeoxycholic acid are at high risk for disease progression. Fibrates, which are agonists of peroxisome proliferator–activated ...
Show more >Background Patients with primary biliary cholangitis who have an inadequate response to therapy with ursodeoxycholic acid are at high risk for disease progression. Fibrates, which are agonists of peroxisome proliferator–activated receptors, in combination with ursodeoxycholic acid, have shown potential benefit in patients with this condition. Methods In this 24-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 100 patients who had had an inadequate response to ursodeoxycholic acid according to the Paris 2 criteria to receive bezafibrate at a daily dose of 400 mg (50 patients), or placebo (50 patients), in addition to continued treatment with ursodeoxycholic acid. The primary outcome was a complete biochemical response, which was defined as normal levels of total bilirubin, alkaline phosphatase, aminotransferases, and albumin, as well as a normal prothrombin index (a derived measure of prothrombin time), at 24 months. Results The primary outcome occurred in 31% of the patients assigned to bezafibrate and in 0% assigned to placebo (difference, 31 percentage points; 95% confidence interval, 10 to 50; P<0.001). Normal levels of alkaline phosphatase were observed in 67% of the patients in the bezafibrate group and in 2% in the placebo group. Results regarding changes in pruritus, fatigue, and noninvasive measures of liver fibrosis, including liver stiffness and Enhanced Liver Fibrosis score, were consistent with the results of the primary outcome. Two patients in each group had complications from end-stage liver disease. The creatinine level increased 5% from baseline in the bezafibrate group and decreased 3% in the placebo group. Myalgia occurred in 20% of the patients in the bezafibrate group and in 10% in the placebo group. Conclusions Among patients with primary biliary cholangitis who had had an inadequate response to ursodeoxycholic acid alone, treatment with bezafibrate in addition to ursodeoxycholic acid resulted in a rate of complete biochemical response that was significantly higher than the rate with placebo and ursodeoxycholic acid therapy. (Funded by Programme Hospitalier de Recherche Clinique and Arrow Génériques; BEZURSO ClinicalTrials.gov number, NCT01654731. opens in new tab.)Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Inserm
Université de Lille
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Research team(s) :

Inflammatory digestive disease : pathophysiology and therapeutic targets developement
Immunity, inflammation and fibrsis in auto and allo-reactivity

Submission date :

2019-03-01T14:26:55Z
2024-02-06T13:47:58Z