title: Telaprevir for retreatment of HCV infection.
abstract: BACKGROUND
  Up to 60% of patients with hepatitis C virus (HCV) genotype 1 infection do not have a sustained virologic response to therapy with peginterferon alfa plus ribavirin.
  
  
  METHODS
  In this randomized, phase 3 trial, we evaluated the addition of telaprevir to peginterferon alfa-2a plus ribavirin in patients with HCV genotype 1 infection who had no response or a partial response to previous therapy or who had a relapse after an initial response. A total of 663 patients were assigned to one of three groups: the T12PR48 group, which received telaprevir for 12 weeks and peginterferon plus ribavirin for a total of 48 weeks; the lead-in T12PR48 group, which received 4 weeks of peginterferon plus ribavirin followed by 12 weeks of telaprevir and peginterferon plus ribavirin for a total of 48 weeks; and the control group (PR48), which received peginterferon plus ribavirin for 48 weeks. The primary end point was the rate of sustained virologic response, which was defined as undetectable HCV RNA 24 weeks after the last planned dose of a study drug.
  
  
  RESULTS
  Rates of sustained virologic response were significantly higher in the two telaprevir groups than in the control group among patients who had a previous relapse (83% in the T12PR48 group, 88% in the lead-in T12PR48 group, and 24% in the PR48 group), a partial response (59%, 54%, and 15%, respectively), and no response (29%, 33%, and 5%, respectively) (P<0.001 for all comparisons). Grade 3 adverse events (mainly anemia, neutropenia, and leukopenia) were more frequent in the telaprevir groups than in the control group (37% vs. 22%).
  
  
  CONCLUSIONS
  Telaprevir combined with peginterferon plus ribavirin significantly improved rates of sustained virologic response in patients with previously treated HCV infection, regardless of whether there was a lead-in phase. (Funded by Tibotec and Vertex Pharmaceuticals; REALIZE ClinicalTrials.gov number, NCT00703118.).
authors.affiliation: Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany. zeuzem@em.uni-frankfurt.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Pietro
authors.initials: P
authors.lastname: Andreone
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
authors.forename: Moises
authors.initials: M
authors.lastname: Diago
authors.forename: Stuart
authors.initials: S
authors.lastname: Roberts
authors.forename: Roberto
authors.initials: R
authors.lastname: Focaccia
authors.forename: Zobair
authors.initials: Z
authors.lastname: Younossi
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.forename: Andrzej
authors.initials: A
authors.lastname: Horban
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.forename: Frederik
authors.initials: F
authors.lastname: Nevens
authors.forename: Beat
authors.initials: B
authors.lastname: Müllhaupt
authors.forename: Paul
authors.initials: P
authors.lastname: Pockros
authors.forename: Ruben
authors.initials: R
authors.lastname: Terg
authors.forename: Daniel
authors.initials: D
authors.lastname: Shouval
authors.forename: Bart
authors.initials: B
authors.lastname: van Hoek
authors.forename: Ola
authors.initials: O
authors.lastname: Weiland
authors.forename: Rolf
authors.initials: R
authors.lastname: Van Heeswijk
authors.forename: Sandra
authors.initials: S
authors.lastname: De Meyer
authors.forename: Don
authors.initials: D
authors.lastname: Luo
authors.forename: Griet
authors.initials: G
authors.lastname: Boogaerts
authors.forename: Ramon
authors.initials: R
authors.lastname: Polo
authors.forename: Gaston
authors.initials: G
authors.lastname: Picchio
authors.forename: Maria
authors.initials: M
authors.lastname: Beumont
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; D005838:Genotype; 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; D012008:Recurrence; D019233:Retreatment; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; 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; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a