title: Extended treatment with pegylated interferon alfa/ribavirin in patients with genotype 2/3 chronic hepatitis C who do not achieve a rapid virological response: final analysis of the randomised N-CORE trial.
abstract: OBJECTIVE
  The combination of pegylated interferon alfa/ribavirin will likely remain the treatment of choice for HCV genotype 2/3 patients in financially constrained countries for the foreseeable future. Patients with poor on-treatment response may benefit from treatment extension. This study examined the effect of 48 versus 24 weeks of peginterferon alfa-2a/ribavirin on the sustained virological response (SVR) in patients with HCV genotype 2/3 who did not achieve rapid virological response (RVR).
  
  
  METHODS
  N-CORE was a multicentre, randomised, phase III study. HCV genotype 2/3 patients receiving peginterferon alfa-2a/ribavirin without a rapid but with an early virological response were randomised at week 24 to stop treatment (Arm A) or continue to 48 weeks (Arm B). The primary efficacy endpoint was SVR.
  
  
  RESULTS
  Two hundred thirty-five patients were enrolled. End of treatment response was similar in both treatment arms. SVR24 rates were not significantly greater in the extended treatment arm compared with the standard 24-week treatment in either the intention-to-treat or the per-protocol populations (61 vs. 52 %, p = 0.1934 and 63 vs. 52 %, p = 0.1461, respectively). Serious adverse events occurred more frequently in patients receiving extended treatment duration (12 %) versus 24-week therapy (4 %).
  
  
  CONCLUSIONS
  It is unclear whether the extension of peginterferon alfa-2a/ribavirin treatment may benefit HCV genotype 2/3 patients who do not achieve RVR. The study was stopped early because recruitment was slower than anticipated, and this may have limited the statistical impact of these findings.
authors.affiliation: Liver Institute of Virginia, Bon Secours Health System, Richmond and Newport News, 5855 Bremo Road, Suite 509, Richmond, VA, 23226, USA. mitchell_shiffman@bshsi.org.
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.affiliation: Department of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. drhugo@terra.com.br.
authors.forename: Hugo
authors.initials: H
authors.lastname: Cheinquer
authors.affiliation: Department of Internal Medicine, Medizinische Universitätsklinik Tübingen, Tübingen, Germany. christoph.berg@med.uni-tuebingen.de.
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Berg
authors.affiliation: Hepatology Section, Department of Gastroenterology and Rheumatology, Universitätsklinikum Leipzig, Leipzig, Germany. thomas.berg@medizin.uni-leipzig.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.affiliation: Hospital Geral, Santa Casa da Misericórdia do Rio de Janeiro, Rio de Janeiro, Brazil. claudiofigueiredomendes@gmail.com.
authors.forename: Cláudio
authors.initials: C
authors.lastname: de Figueiredo-Mendes
authors.affiliation: Kirby Institute, The University of New South Wales and St. Vincent's Hospital, Sydney, NSW, Australia. gdore@kirby.unsw.edu.au.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.affiliation: Department of Gastroenterology, Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil. marialucia.ferraz@uol.com.br.
authors.forename: Maria Lúcia
authors.initials: ML
authors.lastname: Ferraz
authors.affiliation: Infectious Diseases Research Unit, ABC Foundation Medical School, Santo André, Brazil. cassiamc@uol.com.br.
authors.forename: Maria Cássia
authors.initials: MC
authors.lastname: Mendes-Corrêa
authors.affiliation: Medical Sciences, Pontifícia Universidade Católica de Campinas, São Paulo, Brazil. mariapatelli@uol.com.br.
authors.forename: Maria Patelli
authors.initials: MP
authors.lastname: Lima
authors.affiliation: Department of Gastroenterology, Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil. drerparise@terra.com.br.
authors.forename: Edison R
authors.initials: ER
authors.lastname: Parise
authors.affiliation: Centro de Investigación Farmacéutica Especializada, Guadalajara, JAL, Mexico. draampr@yahoo.com.mx.
authors.forename: Alma Minerva Perez
authors.initials: AM
authors.lastname: Rios
authors.affiliation: Centre for Infectious Diseases, Universidade Federal do Espírito Santo, Vitória, Brazil. tania.reuter@gmail.com.
authors.forename: Tania
authors.initials: T
authors.lastname: Reuter
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. asanyal@mcvh-vcu.edu.
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Sanyal
authors.affiliation: Division of Infectious Diseases, University of Alberta, Edmonton, AB, Canada. sshafran@ualberta.ca.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Shafran
authors.affiliation: IST GmbH, Mannheim, Germany. marc.hohmann@ISTGmbH.com.
authors.forename: Marc
authors.initials: M
authors.lastname: Hohmann
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland. fernando.tatsch@abbvie.com.|AbbVie, Chicago, IL, USA. fernando.tatsch@abbvie.com.
authors.forename: Fernando
authors.initials: F
authors.lastname: Tatsch
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland. george.bakalos@roche.com.
authors.forename: George
authors.initials: G
authors.lastname: Bakalos
authors.affiliation: Department of Medicine 1, J.W. Goethe University Hospital, Frankfurt, Germany. zeuzem@em.uni-frankfurt.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
keywords: Chronic hepatitis C; Genotype 2/3; Hepatitis C virus; N-CORE; Peginterferon/ribavirin; Slow virological responders