Lower-Dose Therapy Controls HCV
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By Charles Bankhead, Staff Writer, MedPage Today
Published: August 05, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

http://www.medpagetoday.com/InfectiousDisease/Hepatitis/15388

* Explain to patients that in this study a low-dose antiviral therapy for
hepatitis C infection proved as effective as standard-dose therapy.

Hepatitis C (HCV) therapy based on low-dose peginterferon alpha-2b (Peg-Intron)
achieved a sustained virologic response rate and tolerability comparable to a
higher dose of alpha-2b and peginterferon alpha-2a (Pegasys), a multicenter
clinical trial found.

Rates of sustained virologic response ranged from 38% to 41% among the three
regimens. Relapse rates were similar among the three treatment groups, and
serious adverse events occurred in 9% to 12% of patients in each group.

The findings came as a surprise, given evidence of a higher rate of sustained
response in patients treated with standard-dose peginterferon alpha-2b.

"We aimed to test the hypothesis that use of standard-dose peginterferon
alpha-2b with ribavirin would result in a higher rate of sustained virologic
response than with the low-dose regimen," John G. McHutchison, MD, of Duke
University in Durham, N.C., and colleagues reported in the Aug. 6 New England
Journal of Medicine.

"Although our data do not support this hypothesis, a significant interaction
between treatment group and sex suggests that women may have higher rates of
sustained virologic response with standard-dose than with low-dose peginterferon
alpha-2b."

Treatment guidelines for hepatitis C infection recommend peginterferon alpha-2a
or alpha-2b in combination with ribavirin. However, comparative data on the two
therapies have been scant.

In an effort to clarify their relative effectiveness and safety, investigators
at 118 sites in the U.S. randomized 3,070 patients with HCV genotype 1 to one of
three treatment groups:

* peginterferon alpha-2b at a standard dose of 1.5mcg/kg/week plus ribavirin
800 to 1400 mg/d
* peginterferon alpha-2b at a low dose of 1.0 mcg/kg/week plus ribavirin 800
to 1400 mg/d
* peginterferon alpha-2a at a dose of 180 mcg/week plus ribavirin 1000 to
1200 mg/d

Randomized treatment continued for a maximum of 48 weeks, and patients were
followed for an additional 24 weeks.

The primary endpoint was sustained virologic response, defined as undetectable
HCV RNA 24 weeks after completion of therapy.

When the study ended, rates of sustained virologic response were 38% with
low-dose peginterferon alpha-2b, 39.8% with standard-dose alpha-2b, and 40.9%
with peginterferon alpha-2a.

Relapse rates were 20% with low-dose peginterferon alpha-2b, 23.5% with
standard-dose alpha-2b, and 31.5% for peginterferon alfa-2a.

Overall, patients who had undetectable HCV RNA levels after four and 12 weeks of
treatment had sustained virologic response rates of 86.2% and 78.7%,
respectively.

Higher ribavirin doses were associated with an increased likelihood of sustained
virologic response in all three treatment groups, the authors said.

Patients who weighed 75 to 85 kg received 1000 mg of ribavirin if they were
randomized to peginterferon alpha-2b and 1200 mg if they received peginterferon
alpha-2a.

In these heavier patients, the sustained response rate was about 10 percentage
points higher in the peginterferon alpha-2a group, suggesting that larger
patients treated with peginterferon alpha-2b also should receive the higher dose
of ribavirin.

Although the overall results did not support the superiority of standard-dose
peginterferon alpha-2b, female patients in the standard-dose group had a
sustained virologic response rate of 44.3% compared with 35.9% in the low-dose
alpha-2b group.

The authors found a significant interaction between treatment group and sex
(P=0.01), suggesting that women may do better with standard-dose peginterferon
alpha-2b.

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