Pegylated
Interferon Alfa-2a (Pegasys) Continues to Suppress HBV in PEG for B Trial, but
Adding Adefovir (Hepsera) Provides No Extra Benefit By
Liz Highleyman  Several
nucleoside/nucleotide analogs are approved for the treatment
of chronic hepatitis B virus (HBV) infection, but their long-term effectiveness
is limited by the emergence of drug-resistant virus. Another approved hepatitis
B therapy, pegylated
interferon, works by modulating the immune response against the virus.
The
multicenter Italian PEG for B study compared the safety and efficacy of pegylated
interferon monotherapy vs pegylated interferon plus the nucleotide analog
adefovir (Hepsera). The trial
included 60 participants (67% men; median age 48 years) with chronic hepatitis
B "e" antigen (HBeAg) negative infection.
All patients had
HBV DNA viral loads of 104 copies/mL or greater, elevated alanine aminotransferase
(ALT) levels, and compensated liver disease. The mean baseline HBV DNA level was
6.4 log copies/mL and the mean ALT level was 3.3 times the upper limit of normal.
Individuals with hepatitis C virus (HCV) or
HIV coinfection, as well as those with clinical signs of cirrhosis, were not included.
Participants
were randomly assigned (1:1) to receive 180 mcg/week pegylated interferon alfa-2a
(Pegasys)
monotherapy or pegylated
interferon plus 10 mg adefovir
for 48 weeks, followed by 24 weeks of post-treatment observation. Baseline characteristics
were comparable in both groups.
The
primary study endpoint was sustained virological response (SVR), defined as serum
HBV DNA < 104 copies/mL at the end of the post-treatment observation period.
Preliminary
24-week data from the study were presented at the European Association for
the Study of the Liver (EASL) annual meeting in April 2007. More recently, at
the Digestive Disease Week 2008 conference last month
in San Diego, Paola Piccolo and colleagues presented longer-term, 48-week outcomes. Results
•
After
48 weeks of antiviral treatment, 69% of patients in the combination therapy group
had undetectable HBV DNA, compared with 32% in the pegylated interferon monotherapy
group (P < 0.01).
•
ALT
normalization occurred in 55% and 25%, respectively (P < 0.05).
•
At
the end of post-treatment follow-up, about 80% of patients in both groups experienced
virological relapse.
•
21%
in the combination therapy group and 18% in the monotherapy group achieved SVR
(not a significant difference).
•
Mean
post-treatment serum HBV DNA levels were about 5 log copies/mL in both groups.
•
Post-treatment
ALT levels increased to about 4 times the upper limit of normal in both groups.
•
1
patient in the combination therapy group, but none in the monotherapy arm, achieved
hepatitis B surface antigen (HBsAg) loss.
•
In
a multiple regression analysis, SVR was associated with a lower baseline fibrosis
score.
•
13%
of participants in both groups discontinued therapy early due to adverse events.
•
Nearly
25% required pegylated interferon dose reduction to manage side effects.
Conclusion "In
HBeAg negative chronic hepatitis B, combination pegylated interferon plus adefovir
treatment for 48 weeks is safe, and results in greater serum HBV DNA suppression
and ALT normalization than pegylated interferon monotherapy," the study investigators
concluded. However,
they added, "after 24 weeks of follow-up there is no difference in SVR and
ALT levels between the two treatment regimens."
6/03/08
Reference
P
Piccolo, L De Melia, F Bandiera, and others. Peginterferon alpha-2a plus adefovir
dipivoxil vs. peginterferon alpha-2a monotherapy for 48 weeks in HBeAg-negative
chronic hepatitis B: final results of the PEG for B randomized multicenter trial.
Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22, 2008. Abstract 256.
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