BACKGROUND & AIM:

Mechanisms of non-responsiveness to peginterferon alfa-2a are not completely understood. Inadequate plasma levels may contribute to reduced response. The aim of this prospective, multicentre, crossover phase 1 study was to evaluate the pharmacokinetics and viral kinetics of intravenous versus subcutaneous peginterferon alfa-2a in patients with genotype 1 chronic hepatitis C infection who showed null-response to previous peginterferon/ribavirin.

 

METHODS:

Patients were randomized in 4 treatment arms to subcutaneous or intravenous peginterferon alfa-2a 180μg, once or twice weekly for two weeks. After a wash-out phase of 6 weeks patients first receiving intravenous administration switched to subcutaneous or vice versa for additional two weeks.

 

RESULTS:

Intravenous administration resulted in a stronger and faster decline in HCV RNA with a maximum decline of 1.17 log10 vs. 0.41 log10 after application of pegylated interferon once weekly and 1.32 log10 vs. 0.54 log10 and twice weekly. Pharmacokinetic studies revealed significantly higher maximum concentration (Cmax ) 0-12 h and Cmax 0-7 d following intravenous administration, irrespective of dosing frequency A rapid rebound in HCV RNA was observed in all treatment arms. Adverse events occurred more frequently following intravenous administration.

 

CONCLUSION:

Intravenous administration of peginterferon alfa-2a results in considerably higher plasma concentration and a stronger decline in HCV RNA and offers an interesting approach in order to overcome interferon non-responsive-state in patients with full null-response to previous peginterferon/ribavirin combination therapy.