拉米耐药后恩替治疗效果显著（4月19日于EASL）

zasxz

In HBV Patients Unresponsive to Lamivudine, Entecavir 1.0 Mg Produces Superior Response as Defined by ALT Levels, HBeAg Status, YMDD Mutations, and Genotype Compared to Continuing Lamivudine Entecavir (ETV) is an antiviral with potent, selective activity against wild-type and lamivudine (LVD)-resistant HBV.?At 0.5 and 1.0 mg doses, ETV has demonstrated superior antiviral activity in a phase II dose-ranging study of ETV (0.1, 0.5, 1.0 mg daily) versus continued LVD in LVD-refractory patients.? Response, measured as reduction of HBV DNA by Roche Amplicor? PCR, was evaluated within subgroups defined by baseline disease characteristics: HBeAg status, ALT levels, YMDD mutations, and HBV genotype. P-values were based on linear regression. Results For the therapeutic 1.0mg ETV dose, superiority of ETV to LVD was demonstrated within subgroups.?Analyses by bDNA (LOQ <0.7 MEq/mL) support this conclusion. The authors conclude, 揟he response of 1.0 mg ETV was consistently superior to continued LVD across baseline HBV disease characteristics in a LVD-refractory population. 04/19/04 Reference E R Schiff and others. ENTECAVIR 1.0 MG IS CONSISTENTLY SUPERIOR TO LAMIVUDINE AT 48 WEEKS ACROSS MULTIPLE BASELINE HBV DISEASE CHARACTERISTICS IN LAMIVUDINE-REFRACTORY PATIENTS. Abstract 442.?/b>39th EASL. April 14-18, 2004. Berlin, Germany.

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地天泰

Entecavir at Two Low Doses Demonstrates Potent Anti-HBV Activity in Phase II Trial in China

Entecavir (ETV) is a novel hepatitis B antiviral agent with potent selective activity against the hepatitis B virus (HBV). This is the first phase II trial conducted in China with entecavir.


The purpose of this study is to determine the proportion of subjects in the ETV and placebo treatment groups who demonstrate an antiviral response at the end of the 28-day dosing period as measured by either a ?2 log10 reduction in HBV DNA by bDNA assay or undetectable HBV DNA by bDNA assay plus a ? 2 log10 reduction in HBV DNA by PCR assay.


This is an ongoing study in Chinese adults with chronic hepatitis B infection (HBeAg-positive and -negative) with less than 12 weeks of prior anti-HBV nucleoside therapy. The study has four phases:

(1)     a randomized 28-day double-blind dosing phase of two doses of ETV (0.1 and 0.5 mg once daily) compared with placebo;

(2)     a 56-day post-dosing phase;

(3)     a 48-week open-label ETV 0.5 mg once daily dosing phase; and

(4)     a 24-week post open-label follow-up phase.

Results from the 28-day double blind dosing phase and 56-day post-dosing phase are presented here.


Study Results

216 patients were randomized (1:1:1) in the study and 212 patients received at least one dose of study medication. The majority of the subjects were male (74%), all were Asian, 96% were HBeAg-positive and the mean age was 30 years.

The three treatment groups (ETV 0.1 mg, ETV 0.5 mg, placebo) were similar in terms of median baseline HBV DNA level by bDNA assay (3.18, 3.04, 3.08 MEq/mL, respectively) and median baseline ALT values (57.0, 59.5, 64.0 U/L). Entecavir 0.1 and 0.5 mg doses were superior to placebo for the primary endpoint of reducing HBV DNA levels at Day 28 (86%, 93%, 3%, respectively; p < 0.0001).

The mean change from baseline in HBV DNA levels at Day 28 for the ETV 0.1 mg, 0.5 mg, and placebo groups as determined by bDNA assay were -2.51, -2.73, and -0.12 log10 MEq/mL, respectively. In the 56-day post-dosing phase, the ETV 0.5 mg dose was associated with greater viral suppression than the 0.1 mg dose.

The most common clinical adverse events (> 5% incidence) were fatigue, somnolence, dizziness, insomnia and rhinitis. There were no meaningful differences between the entecavir and placebo groups in the incidence of adverse events on treatment.


Conclusion

Entecavir at both 0.1 and 0.5 mg doses demonstrated potent antiviral activity compared with placebo, as measured by reduction in HBV DNA viral load over a 28-day treatment period. Both the 0.1 and 0.5 mg doses of ETV administered once daily for 28 days were safe and well tolerated.

11/05/03

Reference
G Yao and others. A PHASE II STUDY IN CHINA OF THE SAFETY & ANTIVIRAL ACTIVITY OF ENTECAVIR IN ADULTS WITH CHRONIC HEPATITIS B INFECTION. Abstract 1143 (poster). 54th Annual Meeting of the American Association for the Study of Liver Diseases. October 24-28, 2003. Boston, MA.

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