N Engl J Med. 2011 Mar 31;364(13):1207-17. doi: 10.1056/NEJMoa1009482.

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; HCV RESPOND-2 Investigators.

Collaborators (91)

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.

Source

Saint Louis University School of Medicine, St. Louis, MO 63110-0250, USA. baconbr@slu.edu

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.).

Comment in

A new era of hepatitis C therapy begins. [N Engl J Med. 2011]
A new era of hepatitis C therapy begins.Jensen DM. N Engl J Med. 2011 Mar 31; 364(13):1272-4.
Boceprevir for previously treated chronic hepatitis C virus genotype 1 infection. [J R Coll Physicians Edinb. 2011]
Boceprevir for previously treated chronic hepatitis C virus genotype 1 infection.Bathgate A. J R Coll Physicians Edinb. 2011 Jun; 41(2):122-3.