Boceprevir for untreated chronic HCV genotype 1 infection
Fred Poordad, Jonathan McCone Jr, Bruce R Bacon, Savino Bruno, Michael P Manns, Mark S Sulkowski, Ira M Jacobson, K Rajender Reddy, Zachary D Goodman, Navdeep Boparai, Mark J DiNubile, Vilma Sniukiene, Clifford A Brass, Janice K Albrecht, Jean-Pierre Bronowicki, SPRINT-2 Investigators, L Colombato, J Curciarello, M Silva, H Tanno, R Terg, M Adler, P Langlet, L Lasser, F Nevens, F Anderson, R Bailey, M Bilodeau, C Cooper, S V Feinman, J Heathcote, M Levstik, A Ramji, M Sherman, S Shafran, E Yoshida, A Achim, S Ben Ali, M-A Bigard, C Bonny, M Bourliere, N Boyer-Darrigrand, J-P Bronowicki, V Canva, P Couzigou, V De Ledinghen, D Guyader, C Hezode, D Larrey, M Latournerie, P Marcellin, P Mathurin, M Maynard-Muet, J Moussalli, R Poupon, T Poynard, L Serfaty, A Tran, C Trepo, R Truchi, J-P Zarski, T Berg, N Dikopoulos, C Eisenbach, P R Galle, G Gerken, T Goeser, M Gregor, D Klass, M R Kraus, C Niederau, J F Schlaak, R Schmid, P Thies, K Schmidt, R Thimme, H Weidenbach, S Zeuzem, M Angelico, S Bruno, G Carosi, A Craxì, A Mangia, M Pirisi, M Rizzetto, G Taliani, A L Zignego, H W Reesink, F Serejo, A Reymunde, B Rosado, E Torres, R Barcena Marugan, M De la Mata, J L Calleja, G Castellano, M Diago, R Esteban, C Fernandez-Rodriguez, J Sanchez Tapias, M A Serra Desfilis, N Afdhal, A Al-Osaimi, B Bacon, L Balart, M Bennett, D Bernstein, M Black, C Bowlus, T Boyer, D Dalke, C Davis, G Davis, M Davis, G Everson, F Felizarta, S Flamm, B Freilich, J Galati, G Galler, R Ghalib, A Gibas, E Godofsky, F Gordon, S Gordon, J Gross, S Harrison, J Herrera, S Herrine, K-Q Hu, J Imperial, I Jacobson, D Jones, A Kilby, J King, A Koch, K Kowdley, E Krawitt, P Kwo, L Lambiase, E Lawitz, W Lee, J Levin, R Levine, X Li, A Lok, V Luketic, M Mailliard, J McCone, J McHutchison, D Mikolich, T Morgan, A Muir, Don Nelson, F Nunes, A Nyberg, L Nyberg, P Pandya, M P Pauly, C Peine, G Poleynard, F Poordad, D Pound, J Poulos, M Rabinovitz, N Ravendhran, J Ready, K Reddy, R Reindollar, A Reuben, T Riley, L Rossaro, R Rubin, M Ryan, J Santoro, E Schiff, T Sepe, K Sherman, M Shiffman, M Sjogren, R Sjogren, C Smith, L Stein, R Strauss, M Sulkowski, R Szyjkowski, H Vargas, J Vierling, D Witt, R Yapp, Z Younes, Fred Poordad, Jonathan McCone Jr, Bruce R Bacon, Savino Bruno, Michael P Manns, Mark S Sulkowski, Ira M Jacobson, K Rajender Reddy, Zachary D Goodman, Navdeep Boparai, Mark J DiNubile, Vilma Sniukiene, Clifford A Brass, Janice K Albrecht, Jean-Pierre Bronowicki, SPRINT-2 Investigators, L Colombato, J Curciarello, M Silva, H Tanno, R Terg, M Adler, P Langlet, L Lasser, F Nevens, F Anderson, R Bailey, M Bilodeau, C Cooper, S V Feinman, J Heathcote, M Levstik, A Ramji, M Sherman, S Shafran, E Yoshida, A Achim, S Ben Ali, M-A Bigard, C Bonny, M Bourliere, N Boyer-Darrigrand, J-P Bronowicki, V Canva, P Couzigou, V De Ledinghen, D Guyader, C Hezode, D Larrey, M Latournerie, P Marcellin, P Mathurin, M Maynard-Muet, J Moussalli, R Poupon, T Poynard, L Serfaty, A Tran, C Trepo, R Truchi, J-P Zarski, T Berg, N Dikopoulos, C Eisenbach, P R Galle, G Gerken, T Goeser, M Gregor, D Klass, M R Kraus, C Niederau, J F Schlaak, R Schmid, P Thies, K Schmidt, R Thimme, H Weidenbach, S Zeuzem, M Angelico, S Bruno, G Carosi, A Craxì, A Mangia, M Pirisi, M Rizzetto, G Taliani, A L Zignego, H W Reesink, F Serejo, A Reymunde, B Rosado, E Torres, R Barcena Marugan, M De la Mata, J L Calleja, G Castellano, M Diago, R Esteban, C Fernandez-Rodriguez, J Sanchez Tapias, M A Serra Desfilis, N Afdhal, A Al-Osaimi, B Bacon, L Balart, M Bennett, D Bernstein, M Black, C Bowlus, T Boyer, D Dalke, C Davis, G Davis, M Davis, G Everson, F Felizarta, S Flamm, B Freilich, J Galati, G Galler, R Ghalib, A Gibas, E Godofsky, F Gordon, S Gordon, J Gross, S Harrison, J Herrera, S Herrine, K-Q Hu, J Imperial, I Jacobson, D Jones, A Kilby, J King, A Koch, K Kowdley, E Krawitt, P Kwo, L Lambiase, E Lawitz, W Lee, J Levin, R Levine, X Li, A Lok, V Luketic, M Mailliard, J McCone, J McHutchison, D Mikolich, T Morgan, A Muir, Don Nelson, F Nunes, A Nyberg, L Nyberg, P Pandya, M P Pauly, C Peine, G Poleynard, F Poordad, D Pound, J Poulos, M Rabinovitz, N Ravendhran, J Ready, K Reddy, R Reindollar, A Reuben, T Riley, L Rossaro, R Rubin, M Ryan, J Santoro, E Schiff, T Sepe, K Sherman, M Shiffman, M Sjogren, R Sjogren, C Smith, L Stein, R Strauss, M Sulkowski, R Szyjkowski, H Vargas, J Vierling, D Witt, R Yapp, Z Younes
Abstract
Background: Peginterferon-ribavirin therapy is the current standard of care for chronic infection with hepatitis C virus (HCV). The rate of sustained virologic response has been below 50% in cases of HCV genotype 1 infection. Boceprevir, a potent oral HCV-protease inhibitor, has been evaluated as an additional treatment in phase 1 and phase 2 studies.
Methods: We conducted a double-blind study in which previously untreated adults with HCV genotype 1 infection were randomly assigned 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 (the control group) received placebo plus peginterferon-ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon-ribavirin for 24 weeks, and those with a detectable HCV RNA level between weeks 8 and 24 received placebo plus peginterferon-ribavirin for an additional 20 weeks; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks. Nonblack patients and black patients were enrolled and analyzed separately.
Results: A total of 938 nonblack and 159 black patients were treated. In the nonblack cohort, a sustained virologic response was achieved in 125 of the 311 patients (40%) in group 1, in 211 of the 316 patients (67%) in group 2 (P<0.001), and in 213 of the 311 patients (68%) in group 3 (P<0.001). In the black cohort, a sustained virologic response was achieved in 12 of the 52 patients (23%) in group 1, in 22 of the 52 patients (42%) in group 2 (P=0.04), and in 29 of the 55 patients (53%) in group 3 (P=0.004). In group 2, a total of 44% of patients received peginterferon-ribavirin for 28 weeks. Anemia led to dose reductions in 13% of controls and 21% of boceprevir recipients, with discontinuations in 1% and 2%, respectively.
Conclusions: The addition of boceprevir to standard therapy with peginterferon-ribavirin, as compared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection. The rates were similar with 24 weeks and 44 weeks of boceprevir. (Funded by Schering-Plough [now Merck]; SPRINT-2 ClinicalTrials.gov number, NCT00705432.).
Conflict of interest statement
No other potential conflict of interest relevant to this article was reported.
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Source: PubMed