title: Sustained virologic response rates with telaprevir by response after 4 weeks of lead-in therapy in patients with prior treatment failure.
abstract: OBJECTIVE
  For hepatitis C virus (HCV)-infected patients who have not responded to previous PegIFN/ribavirin treatment, it is unclear whether subsequent direct-acting antiviral therapy outcomes are better predicted by prior treatment response or by on-treatment response to a PegIFN/ribavirin lead-in.
  
  
  METHODS
  In REALIZE, treatment-experienced patients randomized to the lead-in telaprevir arm received 4 weeks of PegIFN-α-2a (180 μg/week) and ribavirin (1000-1200 mg/day), then 12 weeks of telaprevir (750 mg every 8h) plus PegIFN-α-2a/ribavirin, followed by 32 weeks of PegIFN-α-2a/ribavirin. This subanalysis only included patients in the lead-in telaprevir arm with available week 4 on-treatment response data (n=240).
  
  
  RESULTS
  After 4weeks of PegIFN/ribavirin, 90% of relapsers, 60% of partial responders, and 41% of null responders in the lead-in telaprevir arm had ⩾1 log(10) HCV RNA reduction. Sustained virologic response (SVR) rates for telaprevir-treated patients with ≥1 versus <1 log(10) HCV RNA reduction after the PegIFN/ribavirin lead-in were 94% versus 62% in relapsers, 59% versus 56% in partial responders and 54% versus 15% in null responders.
  
  
  CONCLUSIONS
  In prior relapsers and partial responders there is no apparent benefit of assessing response after a PegIFN/ribavirin lead-in with the aim of guiding telaprevir-based treatment. For patients known to be prior null responders, on-treatment response after a 4-week PegIFN/ribavirin lead-in may provide clinically useful prognostic information. However, withholding telaprevir-containing therapy in uncategorised treatment-experienced patient populations (i.e., that could include prior relapsers or partial responders), using response after a PegIFN/ribavirin lead-in could potentially exclude some patients with a high chance of SVR.
authors.affiliation: Queen Marys University of London, Institute of Cell and Molecular Science, London, UK. g.r.foster@qmul.ac.uk
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
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 J
authors.initials: EJ
authors.lastname: Lawitz
authors.forename: Moises
authors.initials: M
authors.lastname: Diago
authors.forename: Stuart
authors.initials: S
authors.lastname: Roberts
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Pockros
authors.forename: Zobair
authors.initials: Z
authors.lastname: Younossi
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lonjon-Domanec
authors.forename: Sandra
authors.initials: S
authors.lastname: De Meyer
authors.forename: Don
authors.initials: D
authors.lastname: Luo
authors.forename: Shelley
authors.initials: S
authors.lastname: George
authors.forename: Maria
authors.initials: M
authors.lastname: Beumont
authors.forename: Gaston
authors.initials: G
authors.lastname: Picchio
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage*; D016879:Salvage Therapy; D017211:Treatment Failure
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a