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A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis

Christophe Corpechot 1, 2 Olivier Chazouillères 1, 2 Alexandra Rousseau 3 Antonia Le Gruyer 4, 5 François Habersetzer 6 Philippe Mathurin 7 Odile Goria 8 Pascal Potier 9 Anne Minello 10 Christine Silvain 11 Armand Abergel 12 Maryline Debette-Gratien 13 Dominique Larrey 14 Olivier Roux 15 Jean-Pierre Bronowicki 16 Jérôme Boursier 17, 18 Victor de Ledinghen 19 Alexandra Heurgue-Berlot 20 Eric Nguyen-Khac 21 Fabien Zoulim 22 Isabelle Ollivier-Hourmand 23 Jean-Pierre Zarski 24 Gisèle Nkontchou 25 Sara Lemoinne 1, 2 Lydie Humbert 26 Dominique Rainteau 26 Guillaume Lefèvre 27, 28, 29 Luc de Chaisemartin 30 Sylvie Chollet-Martin 30 Farid Gaouar 1 Farid Admane 3 Tabassome Simon 3, 31 Raoul Poupon 1, 2
3 Unité de Recherche Clinique de l’Est Parisien [CHU Saint-Antoine]
AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP), CHU Pitié-Salpêtrière [AP-HP]
Abstract : 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.)
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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01951595
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : mardi 11 décembre 2018 - 15:10:50
Dernière modification le : mercredi 14 octobre 2020 - 04:16:56

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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, Massachusetts Medical Society, 2018, 378 (23), pp.2171-2181. ⟨10.1056/NEJMoa1714519⟩. ⟨hal-01951595⟩

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