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

• Published in: Alimentary pharmacology & therapeutics Vol. 26; no. 8; pp. 1131 - 1138
• Main Authors: DIAGO, M., CRESPO, J., OLVEIRA, A., PÉREZ, R., BÁRCENA, R., SÁNCHEZ‐TAPIAS, J. M., MUÑOZ‐SÁNCHEZ, M., ROMERO‐GÓMEZ, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-10-2007; Blackwell
• Subjects: Biological and medical sciences; Digestive system; Gastroenterology. Liver. Pancreas. Abdomen; Medical sciences; Pharmacology. Drug treatments; Antineoplastic agent; Human; Pharmacokinetic pharmacodynamic relationship; Induction; Cytokine; Genotype; Virus; Immunomodulator; Peginterferon alfa-2b; Interferon alpha 2a; Peginterferon alfa-2a; Treatment; Interferon alpha 2b; Antiviral; Clinical trial; Flaviviridae; Pegylated form; Hepatitis C virus; Hepacivirus; Dose
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2007.03470.x

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.