A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis

被引：464

作者：

Corpechot, C. ^{[2
,3
]}

Chazouilleres, O. ^{[2
,3
]}

Rousseau, A. ^{[7
]}

Le Gruyer, A. ^{[9
]}

Habersetzer, F. ^{[10
]}

Mathurin, P. ^{[11
]}

Goria, O. ^{[8
]}

Potier, P. ^{[12
]}

Minello, A. ^{[13
]}

Silvain, C. ^{[14
]}

Abergel, A. ^{[15
]}

Debette-Gratien, M. ^{[16
]}

Larrey, D. ^{[17
]}

Roux, O. ^{[18
]}

Bronowicki, J. -P.

Boursier, J. ^{[20
]}

de Ledinghen, V. ^{[21
]}

Heurgue-Berlot, A. ^{[22
]}

Nguyen-Khac, E. ^{[23
]}

Zoulim, F. ^{[24
]}

Ollivier-Hourmand, I. ^{[25
]}

Zarski, J. -P. ^{[19
,26
]}

Nkontchou, G. ^{[27
]}

Lemoinne, S. ^{[2
,3
]}

Humbert, L. ^{[4
]}

Rainteau, D. ^{[4
]}

Lefevre, G. ^{[5
]}

de Chaisemartin, L. ^{[6
]}

Chollet-Martin, S. ^{[6
]}

Gaouar, F. ^{[2
]}

Admane, F. -H. ^{[7
]}

Simon, T. ^{[1
,7
]}

Poupon, R. ^{[2
,3
]}

机构：

[1] Sorbonne Univ, 184 Rue Faubourg St Antoine, F-75571 Paris 12, France

[2] Paris Sud Univ, St Antoine Univ Hosp, Reference Ctr Inflammatory Biliary Dis & Autoimmu, AP HP,Hepatol & Gastroenterol Dept, Paris, France

[3] Paris Sud Univ, INSERM, S938, UMR, Paris, France

[4] Paris Sud Univ, Biochem Lab, Paris, France

[5] Paris Sud Univ, Sorbonne Univ Biochem Lab, St Antoine Univ Hosp, Tenon Univ Hosp,AP HP,INSERM,Unite 1157,UMR 7203, Paris, France

[6] Paris Sud Univ, Bichat Univ Hosp, AP HP, Immunol Lab,INSERM,UMR S996, Paris, France

[7] Paris Sud Univ, AP HP, Dept Clin Pharmacol & Clin Res Platform East Pari, Paris, France

[8] Rouen Univ Hosp, Hepatol & Gastroenterol Dept, Rouen, France

[9] Pontchaillou Univ Hosp, Hepatol & Gastroenterol Dept, Rennes, France

[10] Univ Strasbourg, Univ Hosp Strasbourg, Hepatol & Gastroenterol Dept,Unite 1110, Inst Viral & Liver Dis,INSERM,Lab Excellence HepS, Strasbourg, France

[11] Claude Huriez Univ Hosp, Hepatol & Gastroenterol Dept, Lille, France

[12] Orleans Hosp, Hepatol & Gastroenterol Dept, Orleans, France

[13] Dijon Bourgogne Univ Hosp, Hepatol & Gastroenterol Dept, Dijon, France

[14] Univ Hosp Poitiers, Hepatol & Gastroenterol Dept, Poitiers, France

[15] Estaing Univ Hosp, Hepatol & Gastroenterol Dept, Clermont Ferrand, France

[16] Univ Hosp Limoges, Hepatol & Gastroenterol Dept, Limoges, France

[17] St Eloi Univ Hosp, Hepatol & Gastroenterol Dept, Montpellier, France

[18] Beaujon Univ Hosp, Hepatol Dept, Clichy, France

[19] Brabois Univ Hosp, Hepatol & Gastroenterol Dept, Nancy, France

[20] Bretagne Loire Univ, Hemodynam Interact Fibrosis & Tumor Invasiveness, Unite Propre Rech Enseignement Super 3859, Univ Hosp Angers,Hepatol & Gastroenterol Dept,Str, Angers, France

[21] Haut Leveque Univ Hosp, Hepatol & Gastroenterol Dept, Pessac, France

[22] Robert Debre Univ Hosp, Hepatol & Gastroenterol Dept, Reims, France

[23] Univ Hosp Amiens, Hepatol & Gastroenterol Dept, Amiens, France

[24] Croix Rousse Univ Hosp, Hepatol & Gastroenterol Dept, Lyon, France

[25] Univ Hosp Caen, Hepatol & Gastroenterol Dept, Caen, France

[26] Michallon Univ Hosp, Hepatol & Gastroenterol Dept, Grenoble, France

[27] Jean Verdier Univ Hosp, Hepatol & Gastroenterol Dept, Bondy, France

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2018年 / 378卷 / 23期

关键词：

URSODEOXYCHOLIC ACID; BIOCHEMICAL RESPONSE; FENOFIBRATE THERAPY; COMBINATION THERAPY; OBETICHOLIC ACID; RENAL-FUNCTION; CIRRHOSIS; OUTCOMES; PROGNOSIS; MULTICENTER;

D O I：

10.1056/NEJMoa1714519

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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.

引用

页码：2171 / 2181

页数：11

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