Clinical trial: pharmacodynamics and pharmacokinetics of re-treatment with fixed-dose induction of peginterferon alpha-2a in hepatitis C virus genotype 1 true non-responder patients.
BACKGROUND
Patients infected with hepatitis C virus genotype 1 who are true non-responders to previous therapy suffer from a very difficult-to-cure disease. New approaches to treatment are necessary.


OBJECTIVE
To explore the efficacy, pharmacokinetics and safety of fixed-dose induction with peginterferon alpha-2a and ribavirin in this difficult-to-cure population.


METHODS
Seventy-five hepatitis C virus genotype 1 true non-responder patients to a previous interferon-based combination regimen were randomised to receive peginterferon alpha-2a 360, 270 or 180 microg/week for 12 weeks, followed by 180 microg/week for 36 weeks, in combination with ribavirin (1000/1200 mg/day). Peginterferon alpha-2a concentration was measured throughout the study.


RESULTS
Sustained virological response rates were 38%, 30% and 18%, in the 360, 270 and 180 microg/week groups, respectively (relapse rates: 25%, 50% and 64%, respectively). The area under the serum concentration-time curve of peginterferon alpha-2a from 0-12 weeks increased in a dose-dependent manner (P < 0.0001) and was associated with the sustained virological response (odds ratio: 1.35; 95% CI: 0.89, 2.06). The three regimens were equally well tolerated.


CONCLUSIONS
Fixed-dose induction of peginterferon alpha-2a resulted in increased drug exposure and improved the likelihood of achieving a cure, without compromising safety in hepatitis C virus genotype 1 true non-responder patients.
Diago
M
M
Hepatology Section, Hospital General de Valencia, Valencia, Spain.
Crespo
J
J
Olveira
A
A
Pérez
R
R
Bárcena
R
R
Sánchez-Tapias
J M
JM
Muñoz-Sánchez
M
M
Romero-Gómez
M
M
D000328:Adult; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a