Universität zu Köln

Hirschfield, Gideon M., Beuers, Ulrich, Kupcinskas, Limas, Ott, Peter, Bergquist, Annika, Faerkkilae, Martti, Manns, Michael P., Pares, Albert ORCID: 0000-0002-5413-9687, Spengler, Ulrich, Stiess, Michael ORCID: 0000-0001-5363-0389, Greinwald, Roland, Prols, Markus, Wendum, Dominique, Drebber, Uta and Poupon, Raoul (2021). A placebo-controlled randomised trial of budesonide for PBC following an insufficient response to UDCA. J. Hepatol., 74 (2). AMSTERDAM: ELSEVIER. ISSN 1600-0641

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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) >1.5x 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 <1.67xULN, 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. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hirschfield, Gideon M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Beuers, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Kupcinskas, Limas UNSPECIFIED UNSPECIFIED UNSPECIFIED Ott, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Bergquist, Annika UNSPECIFIED UNSPECIFIED UNSPECIFIED Faerkkilae, Martti UNSPECIFIED UNSPECIFIED UNSPECIFIED Manns, Michael P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pares, Albert UNSPECIFIED orcid.org/0000-0002-5413-9687 UNSPECIFIED Spengler, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Stiess, Michael UNSPECIFIED orcid.org/0000-0001-5363-0389 UNSPECIFIED Greinwald, Roland UNSPECIFIED UNSPECIFIED UNSPECIFIED Prols, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Wendum, Dominique UNSPECIFIED UNSPECIFIED UNSPECIFIED Drebber, Uta UNSPECIFIED UNSPECIFIED UNSPECIFIED Poupon, Raoul UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-605096
DOI:	10.1016/j.jhep.2020.09.011
Journal or Publication Title:	J. Hepatol.
Volume:	74
Number:	2
Date:	2021
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1600-0641
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PRIMARY BILIARY-CIRRHOSIS; URSODEOXYCHOLIC ACID; ORAL BUDESONIDE; PHARMACOKINETICS; DIAGNOSIS Multiple languages Gastroenterology & Hepatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60509