title: International, multicenter, randomized, controlled study comparing dynamically individualized versus standard treatment in patients with chronic hepatitis C.
abstract: OBJECTIVE
  The aim of this study was to increase virologic response rates by individualized treatment according to the early virologic response.
  
  
  METHODS
  Serum HCV-RNA was frequently quantified in patients with chronic hepatitis C (n=270) treated with peginterferon alfa-2a (180 microg/week) and ribavirin (1000-1200 mg/day). After 6 weeks patients were classified as rapid (RVR), slow (SPR), flat (FPR), or null responders (NUR) and randomized within each viral kinetic class to continue therapy either with an individualized or standard regimen. Individualized therapy comprised peginterferon monotherapy (48 weeks) or shorter combination therapy (24 weeks) for RVR, triple therapy with histamine (1 mg/day) (48 weeks) or prolonged combination therapy (72 weeks) for SPR, triple therapy for FPR, and high-dose peginterferon (360 microg/week) plus ribavirin for NUR patients.
  
  
  RESULTS
  Patients were categorized as RVR (n=171), SPR (n=65), FPR (n=10), or NUR (n=22). Overall end-of-treatment and sustained virologic response rates were 77 and 60% in the individualized and 77 and 66% in the standard treatment arm, respectively. Histamine in addition to peginterferon and ribavirin and high-dose peginterferon plus ribavirin did not improve virologic response rates in patients with FPR and NUR, respectively.
  
  
  CONCLUSIONS
  An improvement in virologic efficacy was not achieved with the available individualized treatment options.
authors.affiliation: Saarland University Hospital, Homburg/Saar, Germany. Zeuzem@uniklinik-saarland.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
authors.forename: Esther
authors.initials: E
authors.lastname: Lukasiewicz
authors.forename: Michael
authors.initials: M
authors.lastname: von Wagner
authors.forename: Ioannis
authors.initials: I
authors.lastname: Goulis
authors.forename: Yoav
authors.initials: Y
authors.lastname: Lurie
authors.forename: Elia
authors.initials: E
authors.lastname: Gianfranco
authors.forename: Jan-Maarten
authors.initials: JM
authors.lastname: Vrolijk
authors.forename: Juan I
authors.initials: JI
authors.lastname: Esteban
authors.forename: Christophe
authors.initials: C
authors.lastname: Hezode
authors.forename: Martin
authors.initials: M
authors.lastname: Lagging
authors.forename: Francesco
authors.initials: F
authors.lastname: Negro
authors.forename: Alexandre
authors.initials: A
authors.lastname: Soulier
authors.forename: Elke
authors.initials: E
authors.lastname: Verheij-Hart
authors.forename: Bettina
authors.initials: B
authors.lastname: Hansen
authors.forename: Ronen
authors.initials: R
authors.lastname: Tal
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrari
authors.forename: Solko W
authors.initials: SW
authors.lastname: Schalm
authors.forename: Avidan U
authors.initials: AU
authors.lastname: Neumann
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects / Q000235:genetics*; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D012449:Safety; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004337:Drug Carriers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a