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.).
Boceprevir for previously treated chronic HCV genotype 1 infection / Bacon BR; Gordon SC; Lawitz E; Marcellin P; Vierling JM; Zeuzem S; Poordad F; Goodman ZD; Sings HL; Boparai N; Burroughs M; Brass CA; Albrecht JK; Esteban R;HCVRESPOND-2 investigators; Delwaide J; Horsmans Y; Van Vlierberghe H; Anderson F; Feinman SV; Heathcote J; Marotta P; Ramji A; Wong F; Peltakian K; Kaita K; Alric L; Ben Ali S; Bigard MA; Bourliere M; Boyer-Darrigrand N; Bronowicki JP; De Ledinghen V; Hezode C; Lebray P; Marcellin P; Maynard-Muet M; Pol S; Poynard T; Tran A; Trepo C; Truchi R; Vallet-Pichard A; Berg T; Guenther R; Lohse AW; Manns MP; Niederau C; Schmidt WE; Spengler U; Wedemeyer H; Zeuzem S; Carosi G; Colombo M; Craxì A; Rizzetto M; Zignego AL; Zuin M; Reymunde A; Buti Ferret M; Esteban R; Afdhal N; Bacon B; Balart L; Bennett M; Box T; Boyer T; Davis M; Flamm S; Freilich B; Galati J; Galler G; Gibas A; Godofsky E; Gordon S; Herrera J; Herrine S; Jacobson I; King J; Kwo P; Lawitz E; Lee W; Levin J; Luketic V; McCone J; McHutchison J; Mullen K; Morgan T; Muir A; Nunes F; Nyberg A; Nyberg L; Pauly MP; Peine C; Ravendhran N; Reindollar R; Riley T; Rossaro L; Rubin R; Ryan M; Schiff E; Sherman K; Shiffman M; Strauss R; Vierling J; Yapp R.. - In: THE NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - STAMPA. - 364(13):(2011), pp. 1207-1217.
Boceprevir for previously treated chronic HCV genotype 1 infection
ZIGNEGO, ANNA LINDA;
2011
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.).File | Dimensione | Formato | |
---|---|---|---|
2011 Bacon NEJM.pdf
Accesso chiuso
Tipologia:
Versione finale referata (Postprint, Accepted manuscript)
Licenza:
Tutti i diritti riservati
Dimensione
622.93 kB
Formato
Adobe PDF
|
622.93 kB | Adobe PDF | Richiedi una copia |
I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.