title: Efficacy and safety of boceprevir plus peginterferon-ribavirin in patients with HCV G1 infection and advanced fibrosis/cirrhosis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, AO Fatebenefratelli e Oftalmico, Milan, Italy. savino.bruno@fbf.milano.it
authors.forename: Savino
authors.initials: S
authors.lastname: Bruno
authors.forename: John M
authors.initials: JM
authors.lastname: Vierling
authors.forename: Rafael
authors.initials: R
authors.lastname: Esteban
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Nyberg
authors.forename: Hugo
authors.initials: H
authors.lastname: Tanno
authors.forename: Zachary
authors.initials: Z
authors.lastname: Goodman
authors.forename: Fred
authors.initials: F
authors.lastname: Poordad
authors.forename: Bruce
authors.initials: B
authors.lastname: Bacon
authors.forename: Keith
authors.initials: K
authors.lastname: Gottesdiener
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Pedicone
authors.forename: Janice K
authors.initials: JK
authors.lastname: Albrecht
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Brass
authors.forename: Seth
authors.initials: S
authors.lastname: Thompson
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Burroughs
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000145:classification*; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008103:Liver Cirrhosis / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011392:Proline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C512204: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; D011392:Proline; C417083:peginterferon alfa-2b