Higher Doses of Pegylated Interferon Increase Rate of HCV Viral Clearance
- Higher Doses of Pegylated Interferon Increase Rate of HCV Viral Clearance
By Brian Boyle, MD
Pegylated interferon plus ribavirin is rapidly moving toward becoming the
standard of care for patients with chronic hepatitis C virus (HCV) infection.
In several studies, it has been shown that this therapy is superior to
standard interferon plus ribavirin therapy, and that the effectiveness of both
pegylated interferon and ribavirin are dose dependent.
Induction therapy with initial high doses of standard interferon plus
ribavirin has been associated with more rapid viral and this increased rate of
clearance may be of particular importance in patients infected with HCV
genotype 1. Therefore, knowledge of viral kinetics in response to high-dose
pegylated interferon plus ribavirin could be important in the design of new
and perhaps more effective therapeutic strategies.
In order to assess the safety and efficacy of high dose pegylated interferon
and ribavirin on the viral kinetics of HCV, 55 previously untreated patients
with chronic hepatitis C caused by HCV genotype 1 were treated with 2
different doses of PEG-Intron (pegylated interferon alfa-2b) plus ribavirin
for 48 weeks. Twenty-eight patients were randomized to receive high-dose
PEG-Intron (3 �g/kg for 1 week, 1.5 �g/kg for 3 weeks, and 1.0 �g/kg for 44
weeks), and 27 patients were randomized to receive a low-dose (0.5 �g/kg) for
48 weeks. Both groups of patients also received 800 mg ribavirin daily. The
mean baseline HCV viral load was similar in both groups (approximately 5.3
During the first 48 hours of treatment, the 3-�g/kg dose of PEG-Intron was
significantly more effective at inhibiting HCV than the 0.5-�g/kg dose (2.08 �
0.93 log vs. 1.09 � 0.80 log; P < .001).
Further, while both increased at 72 hours (0.54 � 0.73 log vs. 0.03 � 0.36
log; P=NS), the high dose showed a greater reduction in HCV viral load at the
end of one week of therapy (1.07 � 0.99 log vs. 0.72 � 0.73 log). Both doses
showed a progressive, but slower, decrease in HCV throughout therapy; however,
HCV RNA became undetectable faster and in more patients with the high dose
than the low dose (22% vs. 7% at week 4, 56% vs. 44% at week 12, 69% vs. 63%
at week 24, and 71% vs. 61.5% at the end of therapy). Both regimens appeared
to be relatively well tolerated.
Of the 55 patients initially enrolled, 49 completed the entire treatment, 24
in the high-dose group and 25 in the low-dose group, with 4 patients in the
high dose group and 2 patients in the low dose group discontinuing therapy
between weeks 3 and 36 due to an adverse event.
The authors conclude, "peginterferon alfa-2b/ribavirin produces an initial
rapid decline in HCV RNA levels, followed by a slower, progressive decrease,
similar to the biphasic kinetic profile of standard combination therapy.
Higher doses of peginterferon alfa-2b also accelerate viral clearance."
Since a significant number of HCV infected patients with genotype 1 do not
achieve sustained virologic response with current therapies, even those that
include pegylated interferons plus ribavirin, the exploration of new
strategies, as presented here, are important and may lead to more effective
initial and salvage therapies for patients chronically infected with HCV.
As the authors note in their discussion of the data, the results of this study
actually may understate the potential of these regimens since some patients in
this study may have been under-dosed regarding PEG-Intron and ribavirin. The
authors recommend that clinicians treating HCV infection should keep in mind
that "to achieve the best response in the future, it will be necessary to
select dosages of peginterferon alfa-2b and ribavirin according to the
patient's body weight in addition to viral load and genotype."
M Buti and others. Viral kinetics in genotype 1 chronic hepatitis C patients
during therapy with 2 different doses of peginterferon alfa-2b plus ribavirin.
Hepatology 2002; 35:930-936.
[Non-text portions of this message have been removed]