title: Reduced dose and duration of peginterferon alfa-2b and weight-based ribavirin in patients with genotype 2 and 3 chronic hepatitis C.
abstract: OBJECTIVE
  There is increasing interest in identifying patients with chronic hepatitis C genotype 2 or 3 infection in whom it is possible to lower the burden of therapy while retaining high levels of efficacy.
  
  
  METHODS
  Treatment-naive patients with chronic hepatitis C genotype 2/3 infection were randomized to receive peginterferon alfa-2b (1.5μg/kg/wk) for 24weeks (group A); peginterferon alfa-2b (1.0μg/kg/wk) for 24weeks (group B); or peginterferon alfa-2b (1.5μg/kg/wk) for 16weeks (group C), each in combination with weight-based ribavirin (800-1200mg/d). The study population comprised two cohorts: the Hep-Net cohort enrolled in Germany and an International cohort enrolled at study sites throughout Europe and Asia. The primary end point was sustained virological response (SVR).
  
  
  RESULTS
  The study included 682 patients; 80.2% had genotype 3 infection. In the intent-to-treat population, SVR rates were 66.5%, 64.3%, and 56.6% in groups A, B, and C, and were similar in Asian and white patients. Treatment differences (A vs. B and A vs. C) failed to reach the predefined margin for noninferiority of -10%; and thus groups B and C failed to show noninferiority relative to group A. Among patients with undetectable HCV RNA at week 4, SVR rates were 75.3%, 75.9%, and 72.4%, respectively. Relapse rates were 17.8%, 16.3%, and 29.3%, respectively. Treatment-emergent serious adverse events were highest in group A and lowest in group C, and adverse events leading to discontinuation were similar across treatment arms.
  
  
  CONCLUSIONS
  For patients with chronic hepatitis C genotype 2/3 infection, 24weeks of peginterferon alfa-2b (1.5μg/kg/wk) plus weight-based ribavirin remains a standard-of-care therapy; however, treatment for 16weeks may be considered for patients with undetectable HCV RNA at week 4 of the treatment.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. Electronic address: manns.michael@mh-hannover.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Manns
authors.affiliation: Department of Medicine I, J.W. Goethe University Hospital, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Dayanand Medical College and Hospital, Ludhiana, Punjab, India.
authors.forename: Ajit
authors.initials: A
authors.lastname: Sood
authors.affiliation: Gastroenterology and Hepatology, Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Lurie
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine II, University of Wurzburg Medical Center, Wurzburg, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Klinker
authors.affiliation: Liver Center Hamburg, IFI-Institute, Hamburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Buggisch
authors.affiliation: Center for Ambulatory Gastroenterology and Endocrinology, Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Rössle
authors.affiliation: Practice for Gastroenterology and Hepatology, Kiel, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Hinrichsen
authors.affiliation: Selayang Hospital, Selangor, Malaysia.
authors.forename: Ismail
authors.initials: I
authors.lastname: Merican
authors.affiliation: Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Ilan
authors.affiliation: Center for HIV and Hepatogastroenterology, Dusseldorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Mauss
authors.affiliation: Hillel-yaffe Medical Center, Hadera, Israel.
authors.forename: Saif
authors.initials: S
authors.lastname: Abu-Mouch
authors.affiliation: Warsaw Medical University & Hospital of Infectious Diseases, Warsaw, Poland.
authors.forename: Andryes
authors.initials: A
authors.lastname: Horban
authors.affiliation: Institute for Medical Informatics, Biometry and Epidemiology, University of Munich, Munich, Germany.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Müller
authors.affiliation: Department of Medicine I, J.W. Goethe University Hospital, Frankfurt, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Welsch
authors.affiliation: Schering-Plough Corporation, Now Merck & Co., Inc., Whitehouse Station, NJ, USA.
authors.forename: Rongdean
authors.initials: R
authors.lastname: Chen
authors.affiliation: Schering-Plough Corporation, Now Merck & Co., Inc., Whitehouse Station, NJ, USA.
authors.forename: Rab
authors.initials: R
authors.lastname: Faruqi
authors.affiliation: Schering-Plough Corporation, Now Merck & Co., Inc., Whitehouse Station, NJ, USA.
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Pedicone
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
mesh_terms: D000328:Adult; D001835:Body Weight; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000208:ethnology / Q000821:virology*; D006801:Humans; D057194:Intention to Treat Analysis; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b