当前位置： SCI文献检索 > JOURNAL OF HEPATOLOGY期刊下所有文献 > A placebo-controlled randomised trial of budesonide for PBC following an insufficient response to UDCA.

A placebo-controlled randomised trial of budesonide for PBC following an insufficient response to UDCA.

Abstract：

BACKGROUND & AIMS:In patients with primary biliary cholangitis (PBC), the efficacy of budesonide, a synthetic corticosteroid displaying high first-pass metabolism, is unresolved. In a placebo-controlled, double-blind trial, we evaluated the added-value of budesonide in those with PBC and ongoing risk of progressive disease despite ursodeoxycholic acid (UDCA) treatment. METHODS:We evaluated 62 patients with PBC who had histologically confirmed hepatic inflammatory activity, according to the Ishak score, and an alkaline phosphatase (ALP) >1.5× upper limit of normal (ULN), after at least 6 months of UDCA therapy. Participants were randomly assigned 2:1 to receive budesonide (9 mg/day) or placebo once daily, for 36 months, with UDCA treatment (12-16 mg/kg body weight/day) maintained. Primary efficacy was defined as improvement of liver histology with respect to inflammation and no progression of fibrosis. Secondary outcomes included changes in biochemical markers of liver injury. RESULTS:Recruitment challenges resulted in a study that was underpowered for the primary efficacy analysis. Comparing patients with paired biopsies only (n = 43), the primary histologic endpoint was not met (p >0.05). The proportion of patients with ALP <1.67×ULN, a ≥15% decrease in ALP and normal bilirubin was higher in the budesonide group than in the placebo group at 12, 24, and 36 months (p <0.05, each). In contrast to placebo, budesonide reduced mean ALP and 35% of budesonide-treated patients achieved normalisation of ALP (placebo 9%; p = 0.023). Serious adverse events occurred in 10 patients receiving budesonide and 7 patients receiving placebo. CONCLUSION:Budesonide add-on therapy was not associated with improved liver histology in patients with PBC and insufficient response to UDCA; however, improvements in biochemical markers of disease activity were demonstrated in secondary analyses. LAY SUMMARY:Around one-third of patients with primary biliary cholangitis (PBC) needs additional medical therapy alongside ursodeoxycholic acid (UDCA) treatment. In this clinical trial, the addition of the corticosteroid budesonide did not improve liver histology; there were however relevant improvements in liver blood tests. CLINICALTRIALS. GOV NUMBER:NCT00746486.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Hirschfield GM,Beuers U,Kupcinskas L,Ott P,Bergquist A,Färkkilä M,Manns MP,Parés A,Spengler U,Stiess M,Greinwald R,Pröls M,Wendum D,Drebber U,Poupon R

doi

10.1016/j.jhep.2020.09.011

subject

Has Abstract

pub_date

2021-02-01 00:00:00

pages

321-329

issue

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(20)33623-0

journal_volume

pub_type

杂志文章

在线工具

A placebo-controlled randomised trial of budesonide for PBC following an insufficient response to UDCA.