Real-world clinical management of patients with primary biliary cholangitis - a retrospective multicenter study from Germany

  • Background: Clinical practice guidelines for patients with primary biliary cholangitis (PBC) have been recently revised and implemented for well-established response criteria to standard first-line ursodeoxycholic acid (UDCA) therapy at 12 months after treatment initiation for the early identification of high-risk patients with inadequate treatment responses who may require treatment modification. However, there are only very limited data concerning the real-world clinical management of patients with PBC in Germany. Objective: The aim of this retrospective multicenter study was to evaluate response rates to standard first-line UDCA therapy and subsequent Second-line treatment regimens in a large cohort of well-characterized patients with PBC from 10 independent hepatological referral centers in Germany prior to the introduction of obeticholic acid as a licensed second-line treatment option. Methods: Diagnostic confirmation of PBC, standard first-line UDCA treatment regimens and response rates at 12 months according to Paris-I, Paris-II, and Barcelona criteria, the follow-up cut-off alkaline phosphatase (ALP) ≤ 1.67 × upper limit of normal (ULN) and the normalization of bilirubin (bilirubin ≤ 1 × ULN) were retrospectively examined between June 1986 and March 2017. The management and hitherto applied second-line treatment regimens in patients with an inadequate response to UDCA and subsequent response rates at 12 months were also evaluated. Results: Overall, 480 PBC patients were included in this study. The median UDCA dosage was 13.2 mg UDCA/kg bodyweight (BW)/d. Adequate UDCA treatment response rates according to Paris-I, Paris-II, and Barcelona criteria were observed in 91, 71.3, and 61.3% of patients, respectively. In 83.8% of patients, ALP ≤ 1.67 × ULN were achieved. A total of 116 patients (24.2%) showed an inadequate response to UDCA according to at least one criterion. The diverse second-line treatment regimens applied led to significantly higher response rates according to Paris-II (35 vs. 60%, p = 0.005), Barcelona (13 vs. 34%, p = 0.0005), ALP ≤ 1.67 × ULN and bilirubin ≤ 1 × ULN (52.1 vs. 75%, p = 0.002). The addition of bezafibrates appeared to induce the strongest beneficial effect in this cohort (Paris II: 24 vs. 74%, p = 0.004; Barcelona: 50 vs. 84%, p = 0.046; ALP < 1.67 × ULN and bilirubin ≤ 1 × ULN: 33 vs. 86%, p = 0.001). Conclusion: Our large retrospective multicenter study confirms high response rates following UDCA first-line standard treatment in patients with PBC and highlights the need for close monitoring and early treatment modification in high-risk patients with an insufficient response to UDCA since early treatment modification significantly increases subsequent response rates of these patients.

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Author:Anne-Christin WildeORCiDGND, Charlotte Lieb, Elise LeichtGND, Lena Maria GreverathORCiDGND, Lara Marleen SteinhagenGND, Nina Wald de ChamorroORCiDGND, Jörg Petersen, Wolf-Peter HofmannORCiDGND, Holger HinrichsenGND, Renate Heyne, Thomas BergORCiDGND, Uwe NaumannGND, Jeannette SchwenzerGND, Johannes VermehrenGND, Andreas Geier, Frank TackeORCiDGND, Tobias MüllerORCiDGND
URN:urn:nbn:de:hebis:30:3-621506
DOI:https://doi.org/10.3390/jcm10051061
ISSN:2077-0383
Parent Title (English):Journal of Clinical Medicine
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Date of Publication (online):2021/03/04
Date of first Publication:2021/03/04
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/10/19
Tag:autoantibodies; primary biliary cholangitis; second line therapy; treatment response; ursodeoxycholic acid
Volume:10
Issue:5, art. 1061
Page Number:11
First Page:1
Last Page:11
Note:
This study was supported by the German Research Foundation Grants MU 2864/1-3 and MU 2864/3-1 and by unrestricted research grants from Intercept Pharmaceuticals and Falk Pharma GmbH. The supporting parties had no influence on the study design, data collection and analyses, writing of the manuscript or on the decision to submit the manuscript for publication.
HeBIS-PPN:48812428X
Institutes:Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0