Predicting efficacy and safety outcomes in patients with hepatitis C virus genotype 1 and persistently 'normal' alanine aminotransferase levels treated with peginterferon alpha-2a (40KD) plus ribavirin

Liver Int. 2008 Jan;28(1):61-71. doi: 10.1111/j.1478-3231.2007.01603.x. Epub 2007 Oct 25.

Abstract

Background: Currently, the approved dosage of ribavirin has not been studied in patients with 'normal' alanine aminotransferase (ALT) levels.

Methods: Modelling and simulations were performed using generalised additive models (GAMs) to predict the incidence of anaemia and rate of sustained virological response (SVR) in patients with hepatitis C virus (HCV) genotype 1 and persistently 'normal' ALT levels treated with peginterferon alpha-2a (40KD) 180 microg/week plus ribavirin 1000/1200 mg/day for 48 weeks.

Results: Model-based simulations predicted that SVR rates would increase from 39 to 48% if patients with genotype 1 and persistently 'normal' ALT levels had received the standard weight-adjusted dose of ribavirin. This was similar to the predicted 49% SVR rate for genotype 1 patients with elevated ALT levels. The incidence of anaemia was predicted to increase from 13% to 23% in patients with persistently 'normal' ALT activity and was higher than that predicted for patients with elevated ALT levels; however, the difference appeared to be largely explained by the higher proportion of women in the former group.

Conclusions: Simulations based on GAM suggest that regimens for patients with HCV genotype 1 should include the standard weight-adjusted dose of ribavirin, as similar SVR rates are predicted to be achieved, regardless of patients' ALT status at baseline.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood*
  • Anemia / etiology*
  • Computer Simulation
  • Dose-Response Relationship, Drug
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Hepacivirus / genetics*
  • Hepatitis C / drug therapy*
  • Hepatitis C / genetics
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Male
  • Models, Theoretical
  • Polyethylene Glycols / therapeutic use*
  • Recombinant Proteins
  • Ribavirin / adverse effects*
  • Ribavirin / therapeutic use
  • Treatment Outcome

Substances

  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Alanine Transaminase
  • peginterferon alfa-2a