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Z Gastroenterol 2024; 62(11): 1931-1942
DOI: 10.1055/a-2382-7720
Originalarbeit

Sub-optimal therapy of patients with primary biliary cholangitis (PBC) in the real-life stetting of the German PBC cohort

Sub-optimale Behandlung von Patienten mit Primär Biliärer Cholangitis (PBC) im klinischen Alltag der deutschen PBC Kohorte
Johannes Wiegand 
1   Division of Hepatology, Department of Medicine II, University Medical Centre, Leipzig, Germany
,
Annegret Franke
2   Clinical Trial Centre of Medical Faculty, University of Leipzig, Leipzig, Germany
,
Tobias Müller
3   Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Charité – Universitätsmedizin Berlin, Berlin, Germany (Ringgold ID: RIN14903)
,
Kerstin Stein
4   Practice of Hepatology Magdeburg, Magdeburg, Germany
,
Heike Bantel
5   Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
,
Rainer Günther
6   Division of Hepatology, Department of Medicine I, Universitätsklinikum Schleswig-Holstein, Kiel, Germany
,
Gerald Denk
7   Department of Medicine II and Transplantation Center, University Hospital, LMU Munich, Munich, Germany (Ringgold ID: RIN54187)
,
Philipp A. Reuken 
8   Department of Internal Medicine IV (Gastroenterology, Hepatology, Infectious diseases), Jena University Hospital, Jena, Germany (Ringgold ID: RIN39065)
,
Jörn M. Schattenberg
9   I. Department of Medicine, Metabolic Liver Research Program, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
,
Uwe Naumann
10   UBN Private Practice, Berlin, Germany
,
Tobias Böttler
11   Department of Medicine II, University Hospital Freiburg, Freiburg, Germany
,
Andreas Weber
12   Department of Internal Medicine 6 Gastroenterology, Hepatology, Endocrinology, Hospital Nuremberg, Nuremberg, Germany (Ringgold ID: RIN9211)
,
Stefan Zeuzem
13   Department of Medicine, Goethe University, University Hospital, Frankfurt am Main, Germany
,
Matthias Hinz
14   Private Practice for Gastroenterology Herne, Herne, Germany
,
Robin Greinert 
15   Department of Gastroenterology, University Hospital Halle, Halle, Germany (Ringgold ID: RIN14942)
,
Christoph Berg
16   Department of Internal Medicine I, University of Tübingen, Tübingen, Germany
,
Thaddäus Till Wissniowski
17   Zentrum Innere Medizin II, Klinikum Chemnitz gGmbH, Chemnitz, Germany (Ringgold ID: RIN14902)
,
Karl-Georg Simon
18   Practice for Gastroenterology, Leverkusen, Germany
,
Jonel Trebicka 
19   Department of Internal Medicine B, University of Münster, Münster, Germany (Ringgold ID: RIN9173)
,
Rüdiger Behrens
20   Private Practice Halle, Halle, Germany
,
Harald Grümmer
21   Practice of Internal Medicine/Gastroenterology, Potsdam, Germany
,
Wolf Peter Hofmann
22   Gastroenterology at Bayerischer Platz, Berlin, Germany
,
Nektarios Dikopoulos
23   Practice for Gastroenterology & Internal Medicine Ludwig & Dikopoulos, Dornstadt, Germany
,
Christoph Sarrazin
24   Medizinische Klinik 2, St. Josef Hospital, Wiesbaden, Germany
,
Elke Roeb
25   Gastroenterology, University of Gießen, Gießen, Germany
,
Andreas E. Kremer
26   Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany
27   Department of Gastroenterology and Hepatology, University Hospital Zürich, Zurich, Switzerland (Ringgold ID: RIN27217)
,
Marion Muche
28   Department of Gastroenterology, Infectious Diseases, and Rheumatology (Campus Benjamin Franklin), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
,
Marc Ringelhan
29   Second Medical Department, University Hospital rechts der Isar, Technical University Munich, School of Medicine, Munich, Germany
,
Andreas Teufel
30   Department of Medicine II, Division of Hepatology, Division of Bioinformatics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
,
Patrick Michl
31   University Hospital Heidelberg, Dept. of Internal Medicine IV, Heidelberg, University of Heidelberg, Heidelberg, Germany
,
Verena Keitel
32   University Hospital Magdeburg, Otto-von Guericke University Magdeburg, Magdeburg, Germany
,
Jens U. Marquardt 
33   Campus Lübeck, First Department of Medicine, University Hospital Schleswig-Holstein, Lübeck, Germany
,
Achim Kautz
34   Kautz5 gUG, Köln, Germany
,
Frank Tacke
3   Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Charité – Universitätsmedizin Berlin, Berlin, Germany (Ringgold ID: RIN14903)
,
Katja Piotrowski
2   Clinical Trial Centre of Medical Faculty, University of Leipzig, Leipzig, Germany
,
Nicole Köppe-Bauernfeind
2   Clinical Trial Centre of Medical Faculty, University of Leipzig, Leipzig, Germany
,
Christian Trautwein
35   Leibniz-Institut für Arbeitsforschung an der TU Dortmund, Dortmund, Germany
,
Thomas Berg
1   Division of Hepatology, Department of Medicine II, University Medical Centre, Leipzig, Germany
› Author AffiliationsThe German PBC Cohort was supported by an unrestricted research grant from Intercept/Advanz Pharma to T.B.
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Abstract

Background

Real-world data on the management of patients with primary biliary cholangitis (PBC) are so far scarce in Germany. Therefore, we aimed to establish a nationwide registry and describe the clinical characteristics and therapy of PBC patients.

Methods

Three different cohorts defined as ursodeoxycholic acid (UDCA) responders, as inadequate responders according to Paris II criteria, and as newly diagnosed patients were prospectively recruited.

This manuscript includes the baseline data of the project.

Results

In total, 33/77 (43%) contacted centres (58% of university hospitals, 38% of non-university hospitals, and 24% of private practices) recruited 515 patients including 204 UDCA responders, 221 inadequate responders to UDCA, and 90 newly diagnosed patients.

All patients were treated with UDCA; however, a UDCA dosage below the recommended dosage of 13 mg/kg/d was observed in 38.5% of individuals after 12 months of treatment. UDCA dosages were lower in nonacademic compared to academic centres.

Only 75/219 (38.5%) of inadequate responders to UDCA received a second-line therapy with obeticholic acid (OCA) and/or bezafibrate (BZF). OCA (13% vs. 4.5%) and BZF (14% vs. 6.5%) were significantly more often prescribed by academic vs. nonacademic centres.

Pruritus (27% vs. 15.5%), fatigue (23% vs. 4.5%), and sicca syndrome (14% vs. 1%) were significantly more often reported by academic centres.

Conclusion

The German PBC registry could be established, which indicates suboptimal therapy in a relevant proportion of patients and shows significant differences between academic and nonacademic centres. Results are fundamental to improving clinical management at different levels of care.

Zusammenfassung

Hintergrund

Es gibt bislang wenige Real-World-Daten zur Primär Biliären Cholangitis (PBC) in Deutschland. Es war daher das Ziel, ein nationales Register zu gründen, um klinische Charakteristika von Patienten mit PBC und deren medikamentöse Therapie zu beschreiben.

Methoden

Es wurden drei Subgruppen innerhalb des Registers definiert: Patienten mit adäquatem Ansprechen auf Ursodeoxycholsäure (UDCA) nach den Paris-II-Kriterien, Patienten mit inadäquatem Therapieansprechen und neu diagnostizierte Patienten. Im vorliegenden Manuskript werden die Patientencharakteristika zum Rekrutierungszeitpunkt in das Register beschrieben.

Ergebnisse

33/77 (43%) kontaktierten Zentren (58% der Universitätskrankenhäuser, 38% der nicht-universitären Krankenhäuser, 24% der Praxen) rekrutierten 515 Patienten (204 UDCA Responder, 221 inadäquate UDCA-Responder, 90 neu diagnostizierte Patienten).

Alle Patienten wurden mit UDCA behandelt, allerdings wurde bei 38,5% der Fälle eine Dosis niedriger als die empfohlene Dosierung von 13 mg/kg/d nach 12 Monaten Therapie beobachtet. Die UDCA-Dosis war an nicht-akademischen Zentren niedriger als an akademischen Zentren.

Nur 75/219 (38.5%) Patienten mit inadäquatem UDCA-Therapieansprechen erhielten eine Behandlung mit Obeticholsäure (OCA) oder Bezafibrat (BZF). OCA (13% vs. 4,5%) und BZF (14% vs. 6,5%) wurden signifikant häufiger von akademischen Zentren verordnet.

Pruritus (27% vs. 15,5%), Müdigkeit (23% vs. 4,5%) und ein Sicca-Syndrom (14% vs. 1%) wurden signifikant häufiger an akademischen Zentren beschrieben.

Zusammenfassung

Das Deutsche PBC-Register konnte erfolgreich gegründet werden, weist auf eine sub-optimale Therapie bei vielen Patienten hin und zeigt signifikante Unterschiede zwischen akademischen und nicht-akademischen Zentren. Die Ergebnisse sind wichtig, um die Versorgung von PBC-Patienten zu verbessern.

Keywords

Ursodeoxycholic acid - obeticholic acid - bezafibrate - pruritus - extrahepatic manifestation

Schlüsselwörter

Ursodeoxycholsäure - Obeticholsäure - Bezafibrat - Juckreiz - extrahepatische Manifestation

Supplementary Material



Publication History

Received: 16 April 2024

Accepted after revision: 02 August 2024

Article published online:
03 September 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol 2017; 67 (01) 145-172
    CrossrefPubMedSearch in Google Scholar
  • 2 [Practice guideline autoimmune liver diseases – AWMF-Reg. No. 021–27]. Z Gastroenterol 2017; 55 (11) 1135-1226
    Thieme ConnectPubMedSearch in Google Scholar
  • 3 Lleo A, Wang GQ, Gershwin ME. et al. Primary biliary cholangitis. Lancet 2020; 396: 1915-1926
    CrossrefPubMedSearch in Google Scholar
  • 4 Harms MH, van Buuren HR, Corpechot C. et al. Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis. J Hepatol 2019; 71 (02) 357-365
    CrossrefPubMedSearch in Google Scholar
  • 5 Wilde AB, Lieb C, Leicht E. et al. Real-World Clinical Management of Patients with Primary Biliary Cholangitis-A Retrospective Multicenter Study from Germany. J Clin Med 2021; 10 (05)
    CrossrefPubMedSearch in Google Scholar
  • 6 Pariente A, Chazouilleres O, Causse X. et al. Management of primary biliary cholangitis: results from a large real-life observational study in France and Belgium. Eur J Gastroenterol Hepatol 2021; 33: e197-e205
    CrossrefPubMedSearch in Google Scholar
  • 7 Cortez-Pinto H, Liberal R, Lopes S. et al. Predictors for incomplete response to ursodeoxycholic acid in primary biliary cholangitis. Data from a national registry of liver disease. United European Gastroenterol J 2021; 9 (06) 699-706
    CrossrefPubMedSearch in Google Scholar
  • 8 Nevens F, Andreone P, Mazzella G. et al. A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis. N Engl J Med 2016; 375 (07) 631-643
    CrossrefPubMedSearch in Google Scholar
  • 9 Corpechot C, Chazouilleres O, Rousseau A. et al. A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis. N Engl J Med 2018; 378 (23) 2171-2181
    CrossrefPubMedSearch in Google Scholar
  • 10 Tanaka A, Hirohara J, Nakano T. et al. Association of bezafibrate with transplant-free survival in patients with primary biliary cholangitis. J Hepatol 2021; 75 (03) 565-571
    CrossrefPubMedSearch in Google Scholar
  • 11 Murillo Perez CF, Fisher H, Hiu S. et al. Greater Transplant-Free Survival in Patients Receiving Obeticholic Acid for Primary Biliary Cholangitis in a Clinical Trial Setting Compared to Real-World External Controls. Gastroenterology 2022; 163 (06) 1630-1642
    CrossrefPubMedSearch in Google Scholar
  • 12 Terziroli Beretta-Piccoli B, Stirnimann G, Cerny A. et al. Geoepidemiology of Primary Biliary Cholangitis: Lessons from Switzerland. Clin Rev Allergy Immunol 2018; 54 (02) 295-306
    CrossrefPubMedSearch in Google Scholar
  • 13 Lammers WJ, Hirschfield GM, Corpechot C. et al. Development and Validation of a Scoring System to Predict Outcomes of Patients With Primary Biliary Cirrhosis Receiving Ursodeoxycholic Acid Therapy. Gastroenterology 2015; 149 (07) 1804-1812
    CrossrefPubMedSearch in Google Scholar
  • 14 Carbone M, Sharp SJ, Flack S. et al. The UK-PBC risk scores: Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cholangitis. Hepatology 2016; 63 (03) 930-950
    CrossrefPubMedSearch in Google Scholar
  • 15 Carbone M, Nardi A, Flack S. et al. Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score. Lancet Gastroenterol Hepatol 2018; 3 (09) 626-634
    CrossrefPubMedSearch in Google Scholar
  • 16 Reig A, Alvarez-Navascues C, Vergara M. et al. Obeticholic Acid and Fibrates in Primary Biliary Cholangitis: Comparative Effects in a Multicentric Observational Study. Am J Gastroenterol 2021; 116 (11) 2250-2257
    CrossrefPubMedSearch in Google Scholar
  • 17 Lammers WJ, Leeman M, Ponsioen CI. et al. How the concept of biochemical response influenced the management of primary biliary cholangitis over time. Neth J Med 2016; 74 (06) 240-246
    PubMedSearch in Google Scholar
  • 18 Sivakumar M, Gandhi A, Shakweh E. et al. Widespread gaps in the quality of care for primary biliary cholangitis in UK. Frontline Gastroenterol 2022; 13 (01) 32-38
    CrossrefPubMedSearch in Google Scholar
  • 19 Kaps L, Grambihler A, Yemane B. et al. Symptom Burden and Treatment Response in Patients with Primary Biliary Cholangitis (PBC). Dig Dis Sci 2020; 65 (10) 3006-3013
    CrossrefPubMedSearch in Google Scholar
  • 20 Sebode M, Kloppenburg A, Aigner A. et al. Population-based study of autoimmune hepatitis and primary biliary cholangitis in Germany: rising prevalences based on ICD codes, yet deficits in medical treatment. Z Gastroenterol 2020; 58 (05) 431-438
    Thieme ConnectPubMedSearch in Google Scholar
  • 21 Corpechot C, Chazouilleres O, Poupon R. Early primary biliary cirrhosis: biochemical response to treatment and prediction of long-term outcome. J Hepatol 2011; 55 (06) 1361-1367
    CrossrefPubMedSearch in Google Scholar
  • 22 Poupon RE, Lindor KD, Cauch-Dudek K. et al. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterology 1997; 113 (03) 884-890
    CrossrefPubMedSearch in Google Scholar
  • 23 Corpechot C, Carrat F, Gaouar F. et al. Liver stiffness measurement by vibration-controlled transient elastography improves outcome prediction in primary biliary cholangitis. J Hepatol 2022; 77 (06) 1545-1553
    CrossrefPubMedSearch in Google Scholar
  • 24 Dupraz J, Le Pogam MA, Peytremann-Bridevaux I. Early impact of the COVID-19 pandemic on in-person outpatient care utilisation: a rapid review. BMJ Open 2022; 12 (03) e056086
    CrossrefPubMedSearch in Google Scholar
  • 25 Abbas N, Smith R, Flack S. et al. Critical shortfalls in the management of PBC: Results of a UK-wide, population-based evaluation of care delivery. JHEP Rep 2024; 6 (01) 100931
    CrossrefPubMedSearch in Google Scholar
  • 26 Wetten A, Jones DEJ, Dyson JK. Specific considerations for the management of primary biliary cholangitis: are the drug treatment options good enough?. Expert Opin Pharmacother 2021; 22 (15) 1949-1953
    CrossrefPubMedSearch in Google Scholar
  • 27 Terracciani F, de Vincentis A, D’Amato D. et al. Long-term real-world experience with obeticholic acid in primary biliary cholangitis: the Italian recapitulate study [Abstract]. J Hepatol 2023; 78: S44
    CrossrefPubMedSearch in Google Scholar
  • 28 D’Amato D, De VA, Malinverno F. et al. Real-world experience with obeticholic acid in patients with primary biliary cholangitis. JHEP Rep 2021; 3 (02) 100248
    CrossrefPubMedSearch in Google Scholar
  • 29 Gomez E, Garcia BL, Molina E. et al. Effectiveness and safety of obeticholic acid in a Southern European multicentre cohort of patients with primary biliary cholangitis and suboptimal response to ursodeoxycholic acid. Aliment Pharmacol Ther 2021; 53 (04) 519-530
    CrossrefPubMedSearch in Google Scholar
  • 30 Corpechot C, Lemoinne S, Soret PA. et al. Adequate vs. deep response to UDCA in PBC: To what extent and under what conditions is normal ALP level associated with complication-free survival gain?. Hepatology 2023;
    CrossrefPubMedSearch in Google Scholar
  • 31 Wiegand J, Franke A, Stein K. et al. Letter to the Editor: Improving access to transient elastography data for real-world prognostic applications in primary biliary cholangitis. Hepatology 2023;
    CrossrefPubMedSearch in Google Scholar
  • 32 Hegade VS, Mells GF, Fisher H. et al. Pruritus Is Common and Undertreated in Patients With Primary Biliary Cholangitis in the United Kingdom. Clin Gastroenterol Hepatol 2019; 17 (07) 1379-1387
    CrossrefPubMedSearch in Google Scholar
  • 33 Mayo MJ, Carey E, Smith HT. et al. Impact of Pruritus on Quality of Life and Current Treatment Patterns in Patients with Primary Biliary Cholangitis. Dig Dis Sci 2023; 68 (03) 995-1005
    CrossrefPubMedSearch in Google Scholar
  • 34 Hirschfield GM, Bowlus CL, Mayo MJ. et al. A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis. N Engl J Med 2024; 390 (09) 783-794
    CrossrefPubMedSearch in Google Scholar
  • 35 Kowdley KV, Bowlus CL, Levy C. et al. Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. N Engl J Med 2024; 390 (09) 795-805
    CrossrefPubMedSearch in Google Scholar