Entecavir
Is More Effective Than Lamivudine in Patients with Chronic
Hepatitis B and Lamivudine Resistance
Lamivudine (Epivir-HBV)
is an effective anti-HBV agent, but is limited by the development
of resistant virus. Entecavir
(Baraclude) is a recently
FDA-approved nucleoside analogue with potent in vitro activity
against lamivudine-resistant hepatitis
B virus (HBV).
In the present dose-ranging, randomized Phase II study, researchers compared
the efficacy and safety of entecavir
with lamivudine in patients with lamivudine-resistant
virus.
Hepatitis B e antigen (HBeAg)-positive
and -negative patients (n = 182), viremic
despite lamivudine treatment for ≥24 weeks or having documented
lamivudine resistance substitutions,
were switched directly to entecavir
(1.0, 0.5, or 0.1 mg daily) or continued on lamivudine
(100 mg daily) for up to 76 weeks.
Results
At week 24, significantly
more patients receiving entecavir
1.0 mg (79%) or 0.5 mg (51%) had undetectable HBV DNA levels
by branched chain DNA assay compared with lamivudine
(13%; P < .0001).
Entecavir 1.0 mg was superior to entecavir
0.5 mg for this end point (P < .01).
After
48 weeks, mean reductions in HBV DNA levels were 5.06, 4.46,
and 2.85 log10 copies/mL on entecavir 1.0, 0.5, and 0.1
mg, respectively, significantly higher than 1.37 log10 copies/mL on lamivudine.
Significantly
higher proportions of patients achieved normalization of
alanine aminotransferase
levels on entecavir 1.0, 0.5,
and 0.1 mg (68%, 59%, and 47%, respectively) than on lamivudine (6%).
One
virologic rebound due to resistance occurred (in the 0.5-mg
group).
In
conclusion, the study authors write, In
HBeAg-positive and HBeAg-negative
lamivudine-refractory patients,
treatment with entecavir 1.0 and 0.5 mg daily was well tolerated and resulted
in significant reductions in HBV DNA levels and normalization
of alanine aminotransferase levels.
One
milligram of entecavir was more effective than 0.5 mg in this population.
11/04/05
Reference
T-T Chang, R G Gish, S J Hadziyannis, and others. A
Dose-Ranging Study of the Efficacy and Tolerability of Entecavir
in Lamivudine-Refractory Chronic
Hepatitis B Patients. Gastroenterology 129(4):
1198-1209. October 2005.
