Boceprevir for previously treated chronic HCV genotype 1 infection
Bruce R Bacon, Stuart C Gordon, Eric Lawitz, Patrick Marcellin, John M Vierling, Stefan Zeuzem, Fred Poordad, Zachary D Goodman, Heather L Sings, Navdeep Boparai, Margaret Burroughs, Clifford A Brass, Janice K Albrecht, Rafael Esteban, HCV RESPOND-2 Investigators, J Delwaide, Y Horsmans, H Van Vlierberghe, F Anderson, S V Feinman, J Heathcote, P Marotta, A Ramji, F Wong, K Peltakian, K Kaita, L Alric, S Ben Ali, M-A Bigard, M Bourliere, N Boyer-Darrigrand, J-P Bronowicki, V De Ledinghen, C Hezode, P Lebray, P Marcellin, M Maynard-Muet, S Pol, T Poynard, A Tran, C Trepo, R Truchi, A Vallet-Pichard, T Berg, R Guenther, A W Lohse, M P Manns, C Niederau, W E Schmidt, U Spengler, H Wedemeyer, S Zeuzem, G Carosi, M Colombo, A Craxì, M Rizzetto, A L Zignego, M Zuin, A Reymunde, M Buti Ferret, R Esteban, N Afdhal, B Bacon, L Balart, M Bennett, T Box, T Boyer, M Davis, S Flamm, B Freilich, J Galati, G Galler, A Gibas, E Godofsky, S Gordon, J Herrera, S Herrine, I Jacobson, J King, P Kwo, E Lawitz, W Lee, J Levin, V Luketic, J McCone, J McHutchison, K Mullen, T Morgan, A Muir, F Nunes, A Nyberg, L Nyberg, M P Pauly, C Peine, N Ravendhran, R Reindollar, T Riley, L Rossaro, R Rubin, M Ryan, E Schiff, K Sherman, M Shiffman, R Strauss, J Vierling, R Yapp, Bruce R Bacon, Stuart C Gordon, Eric Lawitz, Patrick Marcellin, John M Vierling, Stefan Zeuzem, Fred Poordad, Zachary D Goodman, Heather L Sings, Navdeep Boparai, Margaret Burroughs, Clifford A Brass, Janice K Albrecht, Rafael Esteban, HCV RESPOND-2 Investigators, J Delwaide, Y Horsmans, H Van Vlierberghe, F Anderson, S V Feinman, J Heathcote, P Marotta, A Ramji, F Wong, K Peltakian, K Kaita, L Alric, S Ben Ali, M-A Bigard, M Bourliere, N Boyer-Darrigrand, J-P Bronowicki, V De Ledinghen, C Hezode, P Lebray, P Marcellin, M Maynard-Muet, S Pol, T Poynard, A Tran, C Trepo, R Truchi, A Vallet-Pichard, T Berg, R Guenther, A W Lohse, M P Manns, C Niederau, W E Schmidt, U Spengler, H Wedemeyer, S Zeuzem, G Carosi, M Colombo, A Craxì, M Rizzetto, A L Zignego, M Zuin, A Reymunde, M Buti Ferret, R Esteban, N Afdhal, B Bacon, L Balart, M Bennett, T Box, T Boyer, M Davis, S Flamm, B Freilich, J Galati, G Galler, A Gibas, E Godofsky, S Gordon, J Herrera, S Herrine, I Jacobson, J King, P Kwo, E Lawitz, W Lee, J Levin, V Luketic, J McCone, J McHutchison, K Mullen, T Morgan, A Muir, F Nunes, A Nyberg, L Nyberg, M P Pauly, C Peine, N Ravendhran, R Reindollar, T Riley, L Rossaro, R Rubin, M Ryan, E Schiff, K Sherman, M Shiffman, R Strauss, J Vierling, R Yapp
Abstract
Background: In patients with chronic infection with hepatitis C virus (HCV) genotype 1 who do not have a sustained response to therapy with peginterferon-ribavirin, outcomes after retreatment are suboptimal. Boceprevir, a protease inhibitor that binds to the HCV nonstructural 3 (NS3) active site, has been suggested as an additional treatment.
Methods: To assess the effect of the combination of boceprevir and peginterferon-ribavirin for retreatment of patients with chronic HCV genotype 1 infection, we randomly assigned patients (in a 1:2:2 ratio) to one of three groups. In all three groups, peginterferon alfa-2b and ribavirin were administered for 4 weeks (the lead-in period). Subsequently, group 1 (control group) received placebo plus peginterferon-ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon-ribavirin for 32 weeks, and patients with a detectable HCV RNA level at week 8 received placebo plus peginterferon-ribavirin for an additional 12 weeks; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks.
Results: A total of 403 patients were treated. The rate of sustained virologic response was significantly higher in the two boceprevir groups (group 2, 59%; group 3, 66%) than in the control group (21%, P<0.001). Among patients with an undetectable HCV RNA level at week 8, the rate of sustained virologic response was 86% after 32 weeks of triple therapy and 88% after 44 weeks of triple therapy. Among the 102 patients with a decrease in the HCV RNA level of less than 1 log(10) IU per milliliter at treatment week 4, the rates of sustained virologic response were 0%, 33%, and 34% in groups 1, 2, and 3, respectively. Anemia was significantly more common in the boceprevir groups than in the control group, and erythropoietin was administered in 41 to 46% of boceprevir-treated patients and 21% of controls.
Conclusions: The addition of boceprevir to peginterferon-ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with peginterferon-ribavirin alone. (Funded by Schering-Plough [now Merck]; HCV RESPOND-2 ClinicalTrials.gov number, NCT00708500.).
Figures
Source: PubMed