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Z Gastroenterol 2012; 50(1): 57-72
DOI: 10.1055/s-0031-1282015
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© Georg Thieme Verlag KG Stuttgart · New York

Expertenempfehlungen zur Triple-Therapie der HCV-Infektion mit Boceprevir und Telaprevir

Expert Opinion on Boceprevir- and Telaprevir-Based Triple Therapies of Chronic Hepatitis C
C. Sarrazin
1   Klinikum der Goethe-Universität, Medizinische Klinik 1, Frankfurt am Main
,
T. Berg
2   Universitätsklinikum Leipzig, Klinik für Gastroenterologie und Rheumatologie, Sektion Hepatologie, Leipzig
,
M. Cornberg
3   Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
,
M. Dollinger
4   Klinik und Poliklinik für Innere Medizin I, Martin-Luther-Universität, Halle
,
P. Ferenci
5   Univ. Klinik für Innere Medizin 3, Klin. Abteilung für Gastroenterologie und Hepatologie, Medizinische Universität Wien
,
H. Hinrichsen
6   Gastroenterologisch-Hepatologisches Zentrum, Kiel
,
H. Klinker
7   Medizinische Klinik und Poliklinik II, Schwerpunkt Infektiologie, Universitätsklinikum Würzburg
,
M. Kraus
8   Medizinische Klinik II, Kreiskliniken Altötting-Burghausen
,
M. Manns
3   Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
,
S. Mauss
9   Zentrum für HIV und Hepatogastroenterologie, Düsseldorf
,
M. Peck-Radosavljevic
5   Univ. Klinik für Innere Medizin 3, Klin. Abteilung für Gastroenterologie und Hepatologie, Medizinische Universität Wien
,
H. Schmidt
10   Klinik und Poliklinik für Transplantationsmedizin, Universitätsklinikum Münster
,
U. Spengler
11   Medizinische Klinik und Poliklinik I, Universitätsklinikum Bonn
,
H. Wedemeyer
3   Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
,
S. Wirth
12   HELIOS Klinikum Wuppertal, Zentrum für Kinder- und Jugendmedizin, Universität Witten/Herdecke
,
S. Zeuzem
1   Klinikum der Goethe-Universität, Medizinische Klinik 1, Frankfurt am Main
› Author Affiliations
Further Information

Publication History

07 September 2011

23 November 2011

Publication Date:
05 January 2012 (online)

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Zusammenfassung

Mit der aktuell erfolgten Zulassung der beiden Proteaseinhibitoren Boceprevir und Telaprevir zur Behandlung der chronischen Hepatitis C-Virus-Infektion (HCV-Infektion) im Rahmen einer Triple-Therapie in Kombination mit pegyliertem Interferon alpha und Ribavirin ändert sich die Standardtherapie für Patienten mit einer HCV-Genotyp-1-Infektion. Mit der Triple-Therapie kommt es zu einer signifikanten Steigerung der Raten des dauerhaften virologischen Ansprechens von 38 − 44 % auf 63 − 75 % bei der Erstbehandlung bzw. von durchschnittlich 17 − 21 % auf 59 − 66 % bei vortherapierten Patienten im Vergleich zur dualen Kombinationstherapie mit pegyliertem Interferon alpha und Ribavirin allein. Ein wesentlicher Vorteil der Triple-Therapie besteht zudem in der Möglichkeit einer Therapieverkürzung auf 24 − 28 Wochen bei einem Großteil der Patienten mit einer Ersttherapie als auch bei Patienten mit Rückfall auf eine Vortherapie. Allerdings unterscheiden sich die Therapieregime hinsichtlich des Einsatzes einer pegylierten Interferon alpha/Ribavirin-Einleitungsphase („Lead-in“), der Dauer der Gabe des Proteaseinhibitors, der Gesamttherapiedauer, der HCV-RNA-Untersuchungen für eine Therapieverkürzung als auch der Stoppregeln zwischen der Gabe von Boceprevir und Telaprevir erheblich. Weiterhin sind die Entwicklung von viralen Resistenzen, das Management neuer Nebenwirkungen sowie mögliche schwere, klinisch relevante Medikamenteninteraktionen beim Einsatz der beiden Proteaseinhibitoren zu beachten. Das vorliegende Expertenpositionspapier soll einen Überblick über die vorliegenden Daten der klinischen Studien zum Boceprevir und Telaprevir und eine Anleitung zum praktischen Management der Triple-Therapie geben.

Abstract

With the approval of boceprevir and telaprevir the standard treatment of chronic hepatitis C virus (HCV) genotype 1 infection will be the triple therapy of a HCV protease inhibitor together with pegylated interferon alfa and ribavirin. In clinical studies a significant increase of sustained virological response rates from 38 − 44 % to 63 − 75 % for treatment-naïve and from 17 − 21 % to 59 − 66 % in treatment-experienced patients in comparison to the dual combination therapy with pegylated interferon alfa and ribavirin alone has been demonstrated. In addition, a large number of treatment-naïve patients and relapsers benefit from shorten treatment durations to 24 − 28 weeks. However, important differences exist between the administration of boceprevir and telaprevir in terms of a pegylated interferon alfa/ribavirin lead-in phase, the duration of dosing of the protease inhibitor, the overall treatment duration, HCV RNA measurements for response guided treatment durations and stopping rules. Furthermore, triple therapies with boceprevir and telaprevir may be associated with selection of resistant viral variants, new adverse events and clinically relevant drug-drug interactions. The present review gives an overview on the results of underlying clinical studies together with a guideline for the practical management of boceprevir- and telaprevir-based triple therapies.

Schlüsselworter

Virushepatitis - Hepatitis C - Triple-Therapie

Key words

viral hepatitis - hepatitis C - triple therapy
 

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