Gastroenterology
Volume 136, Issue 5 , Pages 1618-1628.e2, May 2009

Peginterferon alfa-2b and Ribavirin: Effective in Patients With Hepatitis C Who Failed Interferon alfa/Ribavirin Therapy

Presented in part at the 55th (2004), 56th (2005), and 57th (2006) Annual Meetings of the American Association for the Study of Liver Diseases; the 40th (2005) and 43rd (2008) Annual Meetings of the European Association for the Study of the Liver; Digestive Diseases Week 2005; and HEP DART 2007: Frontiers in Drug Development for Viral Hepatitis.

  • Thierry Poynard

      Affiliations

    • Service d'hepatologie, Université Pierre et Marie Curie Liver Center, Hôpital La Pitié Salpêtrière, Paris, France
    • Corresponding Author InformationReprint requests Address requests for reprints to: Thierry Poynard, MD, PhD, Hôpital La Pitié Salpêtrière, Université Pierre et Marie Curie Liver Center, Service d'hepatologie, 47-83 boulevard de l'hôpital, 75651 Paris CEDEX 13, France. fax: (11) 33-142-16-14-25
    • ,
  • Massimo Colombo

      Affiliations

    • First Division of Gastroenterology, Fondazione IRCCS Maggiore Hospital, University of Milan, Milan, Italy
    • ,
  • Jordi Bruix

      Affiliations

    • Centro de Investigación Biomédica en Red de Enfermedades Hepaticas y Digestivas, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
    • ,
  • Eugene Schiff

      Affiliations

    • University of Miami School of Medicine, Miami, Florida
    • ,
  • Ruben Terg

      Affiliations

    • Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo, Capital Federal, Argentina
    • ,
  • Steven Flamm

      Affiliations

    • Northwestern University, Chicago, Illinois
    • ,
  • Ricardo Moreno-Otero

      Affiliations

    • Hospital Universitario de la Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepaticas y Digestivas (Instituto de Salud Carlos III), Madrid, Spain
    • ,
  • Flair Carrilho

      Affiliations

    • Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
    • ,
  • Warren Schmidt

      Affiliations

    • University of Iowa Hospitals and Clinics, Iowa City, Iowa
    • ,
  • Thomas Berg

      Affiliations

    • Charité, Campus Virchow Klinikum, Universitätsmedizin Berlin, Germany
    • ,
  • Thomas McGarrity

      Affiliations

    • Milton S. Hershey Medical Center, Hershey, Pennsylvania
    • ,
  • E. Jenny Heathcote

      Affiliations

    • University Health Network, Toronto, ON, Canada
    • ,
  • Fernando Gonçales

      Affiliations

    • Department of Medical Clinical, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil
    • ,
  • Moises Diago

      Affiliations

    • Hospital General Universitario de Valencia, Valencia, Spain
    • ,
  • Antonio Craxi

      Affiliations

    • GI and Liver Unit, DIBIMIS, University of Palermo, Palermo, Italy
    • ,
  • Marcelo Silva

      Affiliations

    • Hospital Universitario Austral, Pilar, Argentina
    • ,
  • Pierre Bedossa

      Affiliations

    • Anatomie Pathologique, Hôpital Beaujon, Clichy, France
    • ,
  • Pabak Mukhopadhyay

      Affiliations

    • Schering–Plough Research Institute, Kenilworth, New Jersey
    • ,
  • Louis Griffel

      Affiliations

    • Schering–Plough Research Institute, Kenilworth, New Jersey
    • ,
  • Margaret Burroughs

      Affiliations

    • Schering–Plough Research Institute, Kenilworth, New Jersey
    • ,
  • Clifford Brass

      Affiliations

    • Schering–Plough Research Institute, Kenilworth, New Jersey
    • ,
  • Janice Albrecht

      Affiliations

    • Schering–Plough Research Institute, Kenilworth, New Jersey
    • ,
  • The Epic Study Group

Received 21 December 2007; accepted 15 January 2009. published online 27 January 2009.

Background & Aims

Treatment with peginterferon alfa and ribavirin produces a sustained virologic response (SVR) in approximately 60% of hepatitis C virus (HCV)-infected patients. Alternate options are needed for patients who relapse or do not respond to therapy.

Methods

This prospective, international, multicenter, open-label study evaluated efficacy and safety of peginterferon alfa-2b (1.5 μg/kg/wk) plus weight-based ribavirin (800–1400 mg/day) in 2333 chronic HCV-infected patients with significant fibrosis/cirrhosis whose previous interferon alfa/ribavirin therapy failed. Patients with undetectable HCV-RNA at treatment week (TW) 12 received 48 weeks of therapy; patients with detectable HCV-RNA at TW12 could enter maintenance studies at TW18; 188 patients with low/detectable HCV-RNA at TW12 continued therapy at the investigator's request.

Results

Overall, 22% of the patients attained SVR (56% with undetectable HCV-RNA and 12% with low/detectable HCV-RNA at TW12). SVR was better in relapsers (38%) than nonresponders (14%), regardless of previous treatment, and in patients previously treated with interferon-alfa/ribavirin (25%) than peginterferon alfa-ribavirin (17%). Predictors of response in patients with undetectable HCV-RNA at TW12 were genotype (2/3 vs 1, respectively; odds ratio [OR] 2.4; P < .0001), fibrosis score (F2 vs F4; OR, 2.2; F3 vs F4; OR, 1.7; P < .0001), and baseline viral load (≤600,000 vs >600,000 IU/mL; OR, 1.4; P = .0223). These factors plus previous treatment and response were overall predictors of SVR. Safety was similar among fibrosis groups.

Conclusions

Peginterferon alfa-2b plus weight-based ribavirin is effective and safe in patients who failed interferon alfa/ribavirin therapy. Genotype, baseline viral load, and fibrosis stage were predictors of response.

Abbreviations used in this paper: EPIC, Evaluation of PegIntron in Control of Hepatitis C Cirrhosis, EVR, early virologic response, HCV, hepatitis C virus, IFN, interferon, LLD, lower limit of detection, PCR, polymerase chain reaction, PEG-IFN, peginterferon, SVR, sustained virologic response, WBD, weight-based dose

 

 Conflicts of Interest The authors disclose the following: T. Poynard, M. Colombo, S. Flamm, T. Berg E. Schiff, E. J. Heathcote, A. Craxi, M. Silva, and W. Schmidt are members of the speakers bureau for Schering–Plough; A. Craxi, E. J. Heathcote, and W. Schmidt are members of the speakers bureau for Roche; T. Poynard, M. Colombo, E. Schiff, M. Diago, S. Flamm, T. Berg, A. Craxi, M. Silva, E. J. Heathcote, and F. Gonçales receive research support from Schering–Plough; A. Craxi receives research support from Roche; S. Flamm receives research support from Valeant and serves on the speakers bureau for Novartis; M. Colombo, E. Schiff, A. Craxi, J. Bruix, and E. J. Heathcote are consultants for Schering–Plough; A. Craxi is a consultant for Roche; L. Griffel, M. Burroughs, C. Brass, J. K. Albrecht, and P. Mukhopadhyay are employees of Schering–Plough Research Institute and stock holders of Schering–Plough; R. Moreno-Otero, F. Carrilho, R. Terg, P. Bedossa, and T. McGarrity have nothing to disclose. Study participants were told of investigators' conflicts of interests.

 Funding Schering–Plough Research Institute fully supported the study. Role of study sponsor: Schering–Plough Research Institute played a major role in the study design. They collected, analyzed, and performed the initial interpretation of all data. All the authors provided input and agreed to the final interpretation. The decision to submit the report was made by Schering–Plough Research Institute in conjunction with the publication committee.

 The complete list of the EPIC Study Group membership appears in the online Appendix.

PII: S0016-5085(09)00102-4

doi:10.1053/j.gastro.2009.01.039

Gastroenterology
Volume 136, Issue 5 , Pages 1618-1628.e2, May 2009