Efficacy and safety of boceprevir plus peginterferon-ribavirin in patients with HCV G1 infection and advanced fibrosis/cirrhosis

J Hepatol. 2013 Mar;58(3):479-87. doi: 10.1016/j.jhep.2012.11.020. Epub 2012 Nov 23.

Abstract

Background & aims: We assessed the safety and efficacy of boceprevir (BOC) plus peginterferon-ribavirin (PR) in patients with HCV-G1 infection and advanced fibrosis/cirrhosis (Metavir F3/F4).

Methods: In two randomized controlled studies of previously untreated and previous treatment failures, patients received a 4-week lead-in of PR followed by PR plus placebo for 44 weeks (PR48); PR plus BOC using response guided therapy (BOC/RGT); or PR plus BOC for 44 weeks (BOC/PR48).

Results: The trials enrolled 178 patients with F3/4. HCV RNA levels at week 4 and 8 were highly predictive of response. No patient with F3/4 in the PR48 arm with a <1 log(10) decline in HCV RNA at week 4 achieved SVR, whereas those randomized to BOC/RGT or BOC/PR48 had SVR rates of 11-33% (F3) and 10-14% (F4). In these latter groups, patients with high baseline viral load (>2 × 10(6)IU/ml) had an overall SVR rate of 6% (2/33). For patients with a ≥1 log(10) decline at week 4, SVR rates in the BOC/PR48 arm of SPRINT-2 and RESPOND-2, respectively, were 77% and 87% vs. 18% and 50% for PR48; SVR rates in early responders (undetectable HCV RNA at week 8) were 90-93% in the BOC/PR48 arm. Neutropenia and thrombocytopenia were more common in cirrhotics than non-cirrhotics.

Conclusions: BOC improves SVR rates in patients with F3/4, and longer treatment duration provides the most benefit. With triple therapy, SVR rates are modest in F4 patients with a <1 log(10) decline at week 4, thus the 4-week PR lead-in aids in the assessment of early futility.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage*
  • Double-Blind Method
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Female
  • Hepacivirus / classification*
  • Hepatitis C / drug therapy*
  • Hepatitis C / virology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / adverse effects
  • Liver Cirrhosis / virology*
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / adverse effects
  • Proline / administration & dosage
  • Proline / adverse effects
  • Proline / analogs & derivatives*
  • RNA, Viral / blood
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Ribavirin / administration & dosage*
  • Ribavirin / adverse effects

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide
  • Proline
  • peginterferon alfa-2b