Telaprevir for retreatment of HCV infection
Stefan Zeuzem, Pietro Andreone, Stanislas Pol, Eric Lawitz, Moises Diago, Stuart Roberts, Roberto Focaccia, Zobair Younossi, Graham R Foster, Andrzej Horban, Peter Ferenci, Frederik Nevens, Beat Müllhaupt, Paul Pockros, Ruben Terg, Daniel Shouval, Bart van Hoek, Ola Weiland, Rolf Van Heeswijk, Sandra De Meyer, Don Luo, Griet Boogaerts, Ramon Polo, Gaston Picchio, Maria Beumont, REALIZE Study Team, Ruben Terg, Marcelo Oscar Silva, Peter Ferenci, Rudolf Stauber, Michael Gschwantler, Martin Weltman, Geoffrey McCaughan, Greg Dore, Hugh Harley, William Sievert, Joe Sasadeusz, Stuart Roberts, Wendy Cheng, Yves Horsmans, Frederik Nevens, Hans Van Vlierberghe, Christophe Moreno, Maria Patelli Lima, Raymundo Parana, Luiz Guilherme Lyra, Cassia Mendes-Correa, Roberto Focaccia, Fernando Lopes Goncales Jr, Curtis Cooper, Richard Lalonde, Eric Yoshida, Marc Bourliere, Jean-Pierre Bronowicki, Patrice Couzigou, Jean-Didier Grange, Patrick Marcellin, Philippe Mathurin, Christian Trepo, Jean-Pierre Zarski, Yves Benhamou, Stanislas Pol, Christophe Hezode, Thomas Berg, Stefan Lueth, Tobias Goeser, Heiner Wedemyer, Stefan Mauss, Jens Rasenack, Stefan Zeuzem, Hans Weidenbach, Yaacov Baruch, Yoav Lurie, Daniel Shouval, Assy Nimer, Ziv Benari, Massimo Colombo, Antonio Ascione, Pietro Andreone, Henk Reesink, Bart van Hoek, Joost Drenth, Robert Flisiak, Andrzej Horban, Wieslaw Kryczka, Maciej Jablkowski, Ewa Janczewska Kazek, Rafael Esteban, Jose Maria Sanchez-Tapias, Maria Trapero, Moises Diago, Javier Garcia-Samaniego, Manuel Romero, Beat Muellhaupt, Tilman Gerlach, Ola Weiland, Geoffrey Dusheiko, David Mutimer, Kaushik Agarwal, Graham R Foster, Ashley Brown, Paul J Pockros, Eliot W Godofsky, Bradley L Freilich, Joseph Galati, Michael Ryan, Coleman Smith, Natalie Bzowej, Gary Davis, Gregory Everson, Norman Gitlin, Stuart C Gordon, Thomas Savides, Eric J Lawitz, David Nelson, Fred Poordad, Maribel Rodriguez-Torres, Velimir A Luketic, Eugene R Schiff, Gyongyi Szabo, Zobair Younossi, Nezam Afdhal, Sanjeev Arora, David Bernstein, Ira M Jacobson, Paul Kwo, James Strohecker, Keyur Patel, Michael Warren Fried, K Rajender Reddy, Mark Sulkowski, Stefan Zeuzem, Pietro Andreone, Stanislas Pol, Eric Lawitz, Moises Diago, Stuart Roberts, Roberto Focaccia, Zobair Younossi, Graham R Foster, Andrzej Horban, Peter Ferenci, Frederik Nevens, Beat Müllhaupt, Paul Pockros, Ruben Terg, Daniel Shouval, Bart van Hoek, Ola Weiland, Rolf Van Heeswijk, Sandra De Meyer, Don Luo, Griet Boogaerts, Ramon Polo, Gaston Picchio, Maria Beumont, REALIZE Study Team, Ruben Terg, Marcelo Oscar Silva, Peter Ferenci, Rudolf Stauber, Michael Gschwantler, Martin Weltman, Geoffrey McCaughan, Greg Dore, Hugh Harley, William Sievert, Joe Sasadeusz, Stuart Roberts, Wendy Cheng, Yves Horsmans, Frederik Nevens, Hans Van Vlierberghe, Christophe Moreno, Maria Patelli Lima, Raymundo Parana, Luiz Guilherme Lyra, Cassia Mendes-Correa, Roberto Focaccia, Fernando Lopes Goncales Jr, Curtis Cooper, Richard Lalonde, Eric Yoshida, Marc Bourliere, Jean-Pierre Bronowicki, Patrice Couzigou, Jean-Didier Grange, Patrick Marcellin, Philippe Mathurin, Christian Trepo, Jean-Pierre Zarski, Yves Benhamou, Stanislas Pol, Christophe Hezode, Thomas Berg, Stefan Lueth, Tobias Goeser, Heiner Wedemyer, Stefan Mauss, Jens Rasenack, Stefan Zeuzem, Hans Weidenbach, Yaacov Baruch, Yoav Lurie, Daniel Shouval, Assy Nimer, Ziv Benari, Massimo Colombo, Antonio Ascione, Pietro Andreone, Henk Reesink, Bart van Hoek, Joost Drenth, Robert Flisiak, Andrzej Horban, Wieslaw Kryczka, Maciej Jablkowski, Ewa Janczewska Kazek, Rafael Esteban, Jose Maria Sanchez-Tapias, Maria Trapero, Moises Diago, Javier Garcia-Samaniego, Manuel Romero, Beat Muellhaupt, Tilman Gerlach, Ola Weiland, Geoffrey Dusheiko, David Mutimer, Kaushik Agarwal, Graham R Foster, Ashley Brown, Paul J Pockros, Eliot W Godofsky, Bradley L Freilich, Joseph Galati, Michael Ryan, Coleman Smith, Natalie Bzowej, Gary Davis, Gregory Everson, Norman Gitlin, Stuart C Gordon, Thomas Savides, Eric J Lawitz, David Nelson, Fred Poordad, Maribel Rodriguez-Torres, Velimir A Luketic, Eugene R Schiff, Gyongyi Szabo, Zobair Younossi, Nezam Afdhal, Sanjeev Arora, David Bernstein, Ira M Jacobson, Paul Kwo, James Strohecker, Keyur Patel, Michael Warren Fried, K Rajender Reddy, Mark Sulkowski
Abstract
Background: Up to 60% of patients with hepatitis C virus (HCV) genotype 1 infection do not have a sustained virologic response to therapy with peginterferon alfa plus ribavirin.
Methods: In this randomized, phase 3 trial, we evaluated the addition of telaprevir to peginterferon alfa-2a plus ribavirin in patients with HCV genotype 1 infection who had no response or a partial response to previous therapy or who had a relapse after an initial response. A total of 663 patients were assigned to one of three groups: the T12PR48 group, which received telaprevir for 12 weeks and peginterferon plus ribavirin for a total of 48 weeks; the lead-in T12PR48 group, which received 4 weeks of peginterferon plus ribavirin followed by 12 weeks of telaprevir and peginterferon plus ribavirin for a total of 48 weeks; and the control group (PR48), which received peginterferon plus ribavirin for 48 weeks. The primary end point was the rate of sustained virologic response, which was defined as undetectable HCV RNA 24 weeks after the last planned dose of a study drug.
Results: Rates of sustained virologic response were significantly higher in the two telaprevir groups than in the control group among patients who had a previous relapse (83% in the T12PR48 group, 88% in the lead-in T12PR48 group, and 24% in the PR48 group), a partial response (59%, 54%, and 15%, respectively), and no response (29%, 33%, and 5%, respectively) (P<0.001 for all comparisons). Grade 3 adverse events (mainly anemia, neutropenia, and leukopenia) were more frequent in the telaprevir groups than in the control group (37% vs. 22%).
Conclusions: Telaprevir combined with peginterferon plus ribavirin significantly improved rates of sustained virologic response in patients with previously treated HCV infection, regardless of whether there was a lead-in phase. (Funded by Tibotec and Vertex Pharmaceuticals; REALIZE ClinicalTrials.gov number, NCT00703118.).
Source: PubMed