title: Telaprevir for previously untreated chronic hepatitis C virus infection.
abstract: BACKGROUND
  In phase 2 trials, telaprevir, a hepatitis C virus (HCV) genotype 1 protease inhibitor, in combination with peginterferon-ribavirin, as compared with peginterferon-ribavirin alone, has shown improved efficacy, with potential for shortening the duration of treatment in a majority of patients.
  
  
  METHODS
  In this international, phase 3, randomized, double-blind, placebo-controlled trial, we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups: a group receiving telaprevir combined with peginterferon alfa-2a and ribavirin for 12 weeks (T12PR group), followed by peginterferon-ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point; a group receiving telaprevir with peginterferon-ribavirin for 8 weeks and placebo with peginterferon-ribavirin for 4 weeks (T8PR group), followed by 12 or 36 weeks of peginterferon-ribavirin on the basis of the same HCV RNA criteria; or a group receiving placebo with peginterferon-ribavirin for 12 weeks, followed by 36 weeks of peginterferon-ribavirin (PR group). The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment (sustained virologic response).
  
  
  RESULTS
  Significantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response (75% and 69%, respectively, vs. 44%; P<0.001 for the comparison of the T12PR or T8PR group with the PR group). A total of 58% of the patients treated with telaprevir were eligible to receive 24 weeks of total treatment. Anemia, gastrointestinal side effects, and skin rashes occurred at a higher incidence among patients receiving telaprevir than among those receiving peginterferon-ribavirin alone. The overall rate of discontinuation of the treatment regimen owing to adverse events was 10% in the T12PR and T8PR groups and 7% in the PR group.
  
  
  CONCLUSIONS
  Telaprevir with peginterferon-ribavirin, as compared with peginterferon-ribavirin alone, was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment, with only 24 weeks of therapy administered in the majority of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ADVANCE ClinicalTrials.gov number, NCT00627926.).
authors.affiliation: Weill Cornell Medical College and Center for the Study of Hepatitis C, New York, NY 10021, USA. imj2001@med.cornell.edu
authors.forename: Ira M
authors.initials: IM
authors.lastname: Jacobson
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Dusheiko
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Di Bisceglie
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.forename: Natalie H
authors.initials: NH
authors.lastname: Bzowej
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Muir
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.forename: Robert
authors.initials: R
authors.lastname: Flisiak
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.forename: Mario
authors.initials: M
authors.lastname: Rizzetto
authors.forename: Daniel
authors.initials: D
authors.lastname: Shouval
authors.forename: Ricard
authors.initials: R
authors.lastname: Sola
authors.forename: Ruben A
authors.initials: RA
authors.lastname: Terg
authors.forename: Eric M
authors.initials: EM
authors.lastname: Yoshida
authors.forename: Nathalie
authors.initials: N
authors.lastname: Adda
authors.forename: Leif
authors.initials: L
authors.lastname: Bengtsson
authors.forename: Abdul J
authors.initials: AJ
authors.lastname: Sankoh
authors.forename: Tara L
authors.initials: TL
authors.lastname: Kieffer
authors.forename: Shelley
authors.initials: S
authors.lastname: George
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kauffman
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D017422:Sequence Analysis, DNA; D015842:Serine Proteinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D012367:RNA, Viral; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D011092:Polyethylene Glycols; C486464:telaprevir; C100416:peginterferon alfa-2a