Effect
of Interferon Alfa-2b Plus Lamivudine vs Lamivudine
Alone on Drug Resistance and on Sustained Response
in HBeAg Negative Chronic Hepatitis B
The
HBeAg
negative form of chronic hepatitis B (CHB)
predominates in the Mediterranean area and has a rising
frequency in Europe and North
America.
At
present there are four FDA-approved therapies for
patients with CHB: interferon-alfa
(Intron A), lamivudine
(Epivir-HBV), and adefovir
dipivoxil (Hepsera).* According to
the author, none of these drugs are effective in achieving
a sustained response in
patients with HBeAg negative CHB.
Therefore,
new therapeutic approaches have been examined. The
aim of the present study was to investigate the efficacy
of combination
treatment of IFN-alfa and lamivudine
compared to lamivudine
monotherapy, after 24 mo of administration
in HBeAg-negative hepatitis B patients.
Fifty
consecutive patients were randomly assigned to receive
IFN-alfa-2b (5 MU thrice per week, n = 24) plus lamivudine
(100 mg daily) or lamivudine only (n = 26) for 24
mo. Patients were followed up for further 6 mo.
The
primary outcome was the proportion with sustained
virological response (undetectable
serum HBV DNA concentrations) and or
sustained biochemical response (transaminase levels
within normal range) at 30 mo (6 mo after the end
of therapy).
Secondary
end-points were timed from initial virological (biochemical)
response to VBR (BBR, respectively) and the emergence
of YMDD
mutants across the two arms.
Results
Five of twenty-four
(21%) patients in the combination arm vs 3/26 (12%)
in the lamivudine arm had sustained response (i.e.,
normal serum
transaminase levels and undetectable
HBV DNA by PCR assay) 6 mo after treatment discontinuation.
A
reduction in the emergence of YMDD mutants and in
the development of virological breakthroughs was observed
in patients receiving combination treatment (10% vs
46%, P = 0.01 and 14% vs 46%, P = 0.03, respectively).
Time
from initial virologic response to virologic breakthrough
(VBR) was greater among initial responders receiving
combination treatment compared to those receiving
lamivudine (22.9 mo vs 15.9 mo, respectively; P =
0.005).
Based
on these results, the study authors conclude, “Our
results demonstrate that IFN-alfa plus lamivudine
combination therapy did not increase the sustained
response, compared to lamivudine [alone].”
“However,
combination therapy reduces the likelihood of VBR
due to YMDD mutants and prolongs the time period until
the breakthrough development.”
* This article
was written prior to the approval of peginterferon
alfa (Pegasys) and entecavir (Baraclude) for the treatment
of CHB [Ed].
Department of Internal Medicine, University of Ioannina
School of Medicine, University Campus, Ioannina 45110,
Greece.
11/09/05
Reference
M
Ecomomou and others. Interferon-alpha plus lamivudine
vs lamivudine reduces breakthroughs, but does not
affect sustained response in HBeAg negative chronic
hepatitis B. World Journal of Gastroenterology 7;11(37): 5882-5887. October 2005.
