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.
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.
Snoeck
Eric
E
Exprimo NV, Mechelen, Belgium.
Hadziyannis
Stephanos J
SJ
Puoti
Claudio
C
Swain
Mark G
MG
Berg
Thomas
T
Marcellin
Patrick
P
Zarski
Jean-Pierre
JP
Jorga
Karin
K
Zeuzem
Stefan
S
D000410:Alanine Transaminase / Q000097:blood*; D000740:Anemia / Q000209:etiology*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008962:Models, Theoretical; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a