Twice‐weekly administration of peginterferon‐α‐2b improves viral kinetics in patients with chronic hepatitis C genotype 1

Abstract

The decline in hepatitis C viral load on treatment with peginterferon-alpha-2b is not continuous. The aim of this study was to investigate whether twice weekly dosing of peginterferon-alpha-2b may improve viral kinetics. Ten interferon-naïve patients with chronic hepatitis C (genotype 1a or b) were randomized to receive either 1.0 microg/kg peginterferon-alpha-2b once (group A) or twice weekly (group B) for 4 weeks. Viral load and serum concentrations of peginterferon-alpha-2b were measured. Peginterferon-alpha-2b reached maximal blood concentrations 24 h after the first dose, followed by a linear decline during the subsequent days. On the day before administration of the next dose, peginterferon-alpha-2b was undetectable in nine patients in group A (once weekly dosing). The same pattern was observed during the next 3 weeks of therapy. In group B (twice weekly dosing) peginterferon-alpha-2b was detectable at any given time point and higher than in group A (P between 0.01 and <0.0001). Viral load decreased in all patients within 2 days after the first dose of peginterferon-alpha-2b, but increased again on day 3. In group A, it further increased until day 7. A similar pattern was observed in the second week. In contrast, in group B, viral load decreased again on day 4 and remained lower until the end of the study (P < 0.001). To achieve continuous drug exposure and to improve initial viral clearance, peginterferon-alpha-2b has to be given at least two times weekly.

Phase 1B, randomized, double-blind, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus

“…In comparison, declines ranging from 0.96 log 10 to 2.11 log 10 have been reported with a single dose of PEG-IFN-␣-2b (1 g/kg and 1.5 g/kg, respectively). 23,24 Similarly, declines ranging from 0.86 log 10 to 1.08 log 10 have been reported for HCV patients injected once with 180 g pegylated IFN-␣-2a. 24,25 Therefore, comparison of immune and antiviral activities induced by CPG 10101 and IFN suggests that CPG 10101 may provide similar antiviral effects and modulation of the innate immune response.…”

“…We measured blood markers of immune response for Days 1 (predose), 2, 8 (predose), 15 (predose), 22 (predose), 23,29,36, and 50 [and Days 4 (predose), 5, 9, and 16 for the twice-weekly dose groups]. We used commercial assays for quantification of 2Ј5Ј-oligoadenylate synthetase (OAS; Eiken Chemical Company, Ltd., Tokyo, Japan), C-reactive protein (Alpco Diagnostics, Windham, NH), and interleukin-18 (Medical and Biological Laboratory, Piscataway, NJ).…”

Predictors of response of U.S. veterans to treatment for the hepatitis C virus

“…PEG-INF 2A and 2B differ in pharmacokinetic properties and HCV RNA clearance kinetics. [22][23][24] The 2 forms also differ in their side-effect profiles. 9,10 Differences in both response while on treatment and side effects may affect continuation of treatment.…”

New Kinetic Models for the Hepatitis C Virus *

“…response (Talal et al, unpublished data). Rebounds have also been reported in patients chronically infected with HCV alone and treated with standard interferon, PEG-IFN ␣-2b, or ␣-2a 13,15,16,32 and may likewise be explained by the pharmacokinetics of the drug. Thus, we believe the approach of incorporating pharmacokinetics and pharmacodynamics into viral dynamic models will also apply to PEG-IFN ␣-2a and possibly to other compounds.…”

“…In responders, the biphasic HCV RNA decline pattern tends to be seen when high daily doses of IFN are used, 1,3,10,14 and more complex patterns tend to be seen when standard thrice-weekly doses or pegylated forms of IFN are used. 4,6,11,15,16 When daily doses of IFN are given to chronically infected patients, the magnitude of the first-phase decline depends on the dose of IFN given, with 10-MU and 15-MU doses leading to larger declines than a 5-MU dose. Neumann et al 1 explained both the speed and the magnitude of the first-phase decline by assuming that IFN partially blocks HCV production from infected cells.…”