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

C. Sarrazin; T. Berg; M. Cornberg; M. Dollinger; P. Ferenci; H. Hinrichsen; H. Klinker; M. Kraus; M. Manns; S. Mauss; M. Peck-Radosavljevic; H. Schmidt; U. Spengler; H. Wedemeyer; S. Wirth; S. Zeuzem

doi:10.1055/s-0031-1282015

Zeitschrift für Gastroenterologie, Table of Contents

Z Gastroenterol 2012; 50(1): 57-72
DOI: 10.1055/s-0031-1282015

Übersicht

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

¹Klinikum der Goethe-Universität, Medizinische Klinik 1, Frankfurt am Main

,

T. Berg

²Universitätsklinikum Leipzig, Klinik für Gastroenterologie und Rheumatologie, Sektion Hepatologie, Leipzig

,

M. Cornberg

³Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover

,

M. Dollinger

⁴Klinik und Poliklinik für Innere Medizin I, Martin-Luther-Universität, Halle

,

P. Ferenci

⁵Univ. Klinik für Innere Medizin 3, Klin. Abteilung für Gastroenterologie und Hepatologie, Medizinische Universität Wien

,

H. Hinrichsen

⁶Gastroenterologisch-Hepatologisches Zentrum, Kiel

,

H. Klinker

⁷Medizinische Klinik und Poliklinik II, Schwerpunkt Infektiologie, Universitätsklinikum Würzburg

,

M. Kraus

⁸Medizinische Klinik II, Kreiskliniken Altötting-Burghausen

,

M. Manns

³Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover

,

S. Mauss

⁹Zentrum für HIV und Hepatogastroenterologie, Düsseldorf

,

M. Peck-Radosavljevic

⁵Univ. Klinik für Innere Medizin 3, Klin. Abteilung für Gastroenterologie und Hepatologie, Medizinische Universität Wien

,

H. Schmidt

¹⁰Klinik und Poliklinik für Transplantationsmedizin, Universitätsklinikum Münster

,

U. Spengler

¹¹Medizinische Klinik und Poliklinik I, Universitätsklinikum Bonn

,

H. Wedemeyer

³Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover

,

S. Wirth

¹²HELIOS Klinikum Wuppertal, Zentrum für Kinder- und Jugendmedizin, Universität Witten/Herdecke

,

S. Zeuzem

¹Klinikum der Goethe-Universität, Medizinische Klinik 1, Frankfurt am Main

› Author Affiliations

Abstract

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

Full Text

References

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