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.).
Boceprevir for untreated chronic HCV genotype 1 infection / Poordad F; McCone J Jr; Bacon BR; Bruno S; Manns MP; Sulkowski MS; Jacobson IM; Reddy KR; Goodman ZD; Boparai N; DiNubile MJ; Sniukiene V; Brass CA; Albrecht JK; Bronowicki JP; SPRINT-2 investigators; Colombato L; Curciarello J; Silva M; Tanno H; Terg R; Adler M; Langlet P; Lasser L; Nevens F; Anderson F; Bailey R; Bilodeau M; Cooper C; Feinman SV; Heathcote J; Levstik M; Ramji A; Sherman M; Shafran S; Yoshida E; Achim A; Ben Ali S; Bigard MA; Bonny C; Bourliere M; Boyer-Darrigrand N; Bronowicki JP; Canva V; Couzigou P; De Ledinghen V; Guyader D; Hezode C; Larrey D; Latournerie M; Marcellin P; Mathurin P; Maynard-Muet M; Moussalli J; Poupon R; Poynard T; Serfaty L; Tran A; Trepo C; Truchi R; Zarski JP; Berg T; Dikopoulos N; Eisenbach C; Galle PR; Gerken G; Goeser T; Gregor M; Klass D; Kraus MR; Niederau C; Schlaak JF; Schmid R; Thies P; Schmidt K; Thimme R; Weidenbach H; Zeuzem S; Angelico M; Bruno S; Carosi G; Craxì A; Mangia A; Pirisi M; Rizzetto M; Taliani G; Zignego AL; Reesink HW; Serejo F; Reymunde A; Rosado B; Torres E; Barcena Marugan R; De la Mata M; Calleja JL; Castellano G; Diago M; Esteban R; Fernandez-Rodriguez C; Sanchez Tapias J; Serra Desfilis MA; Afdhal N; Al-Osaimi A; Bacon B; Balart L; Bennett M; Bernstein D; Black M; Bowlus C; Boyer T; Dalke D; Davis C; Davis G; Davis M; Everson G; Felizarta F; Flamm S; Freilich B; Galati J; Galler G; Ghalib R; Gibas A; Godofsky E; Gordon F; Gordon S; Gross J; Harrison S; Herrera J; Herrine S; Hu KQ; Imperial J; Jacobson I; Jones D; Kilby A; King J; Koch A; Kowdley K; Krawitt E; Kwo P; Lambiase L; Lawitz E; Lee W; Levin J; Levine R; Li X; Lok A; Luketic V; Mailliard M; McCone J; McHutchison J; Mikolich D; Morgan T; Muir A; Nelson D; Nunes F; Nyberg A; Nyberg L; Pandya P; Pauly MP; Peine C; Poleynard G; Poordad F; Pound D; Poulos J; Rabinovitz M; Ravendhran N; Ready J; Reddy K; Reindollar R; Reuben A; Riley T; Rossaro L; Rubin R; Ryan M; Santoro J; Schiff E; Sepe T; Sherman K; Shiffman M; Sjogren M; Sjogren R; Smith C; Stein L; Strauss R; Sulkowski M; Szyjkowski R; Vargas H; Vierling J; Witt D; Yapp R; Younes Z.. - In: THE NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - STAMPA. - 364(13):(2011), pp. 1195-1206.
Boceprevir for untreated chronic HCV genotype 1 infection.
ZIGNEGO, ANNA LINDA;
2011
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.).
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