Clinical trial: pharmacodynamics and pharmacokinetics of re‐treatment with fixed‐dose induction of peginterferon α‐2a in hepatitis C virus genotype 1 true non‐responder patients

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Abstract
Summary: 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.Aim  To explore the efficacy, pharmacokinetics and safety of fixed‐dose induction with peginterferon α‐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 α‐2a 360, 270 or 180 μg/week for 12 weeks, followed by 180 μg/week for 36 weeks, in combination with ribavirin (1000/1200 mg/day). Peginterferon α‐2a concentration was measured throughout the study.Results  Sustained virological response rates were 38%, 30% and 18%, in the 360, 270 and 180 μg/week groups, respectively (relapse rates: 25%, 50% and 64%, respectively). The area under the serum concentration‐time curve of peginterferon α‐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.Conclusion  Fixed‐dose induction of peginterferon α‐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.

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