恩替在治疗E阴性的HBVER优于拉米(11.1 AASLD)

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Entecavir Shows Superior Histologic and Virologic Efficacy Over Lamivudine in Nucleoside-na飗e HBeAg(-) Chronic Hepatitis B

HBeAg(−) chronic hepatitis B can be characterized by a progressive course of severe liver disease activity and has a generally poor long term prognosis. Entecavir (ETV) is a potent and selective inhibitor of hepatitis B virus (HBV) polymerase.

ETV-027 is a multinational, randomized, double-blind Phase III trial comparing ETV to lamivudine/LVD (Epivir-HBV) for up to 96 weeks of blinded dosing in patients with HBeAg(−) chronic hepatitis B.

648 patients were randomized 1:1 to ETV 0.5 mg QD or LVD 100 mg QD. Eligible patients were nucleoside-na飗e, HBeAg(−) and anti-HBe(+), and had HBV DNA ≥ 0.7 MEq/mL by bDNA, and ALT levels 1.3-10 x ULN.

The primary efficacy endpoint, histologic improvement, was the proportion of patients at Week 48 having a > 2-point decrease in Knodell necroinflammatory score and no worsening of fibrosis (worsening: >1 point increase in Knodell fibrosis score).

Secondary efficacy endpoints included proportions with improvement in Ishak fibrosis score, mean reduction of HBV DNA, and proportions achieving the Composite Endpoint (HBV DNA <0.7 MEq/mL by bDNA and ALT normalization (<1.25 x ULN)).

Results

Mean baseline HBV DNA was 7.6 log10 copies/mL by PCR in both groups; mean ALT was 141 and 143 U/L in the ETV and LVD groups, respectively. Results of primary and key secondary endpoints are given below:

Week 48 Study Endpoints (treated patients, non-completer = failure)

EndpointETV 0.5 mg N= 325

LVD 100 mg N= 313

p-value

*咹istologic Improvement

70%

61%

0.0143

咺shak Fibrosis Score Improvement

36%

38%

NS

嘓BV DNA Mean change from baseline by PCR (log10 copies/mL)

−5.20

−4.66

<0.0001

HBV DNA <400 copies/mL by PCR

91%

73%

<0.0001

Composite Endpoint Response

84%

78%

0.0401

*Primary Endpoint ?/sup>n = 296 for ETV and 287 for LVD with evaluable baseline histology ?/sup>n = 314 for ETV and 295 for LVD with Week 48 results

There was no evidence of emergence of ETV resistance in any ETV-treated patients at 48 weeks. Safety was comparable between treatment groups: 6% and 8% of patients in the ETV and LVD groups, respectively, had serious adverse events. At 48 weeks, a greater proportion of ETV than LVD patients achieved the Composite Endpoint and were followed off-treatment for sustained response.

Conclusion

Primary treatment with entecavir was superior to LVD for histologic and virologic response and achievement of the Composite Endpoint, with a comparable safety profile to LVD, in nucleoside-na飗e, HBeAg(−) chronic hepatitis B patients.

11/01/04

Reference Daniel Shouval and others. ENTECAVIR DEMONSTRATES SUPERIOR HISTOLOGIC AND VIROLOGIC EFFICACY OVER LAMIVUDINE IN NUCLEOSIDE-NAIVE HBEAG(−) CHRONIC HEPATITIS B: RESULTS OF PHASE III TRIAL ETV-027.?Abstract LB-07 (oral). 55th AASLD. October 29-November 2, 2004. Boston, MA.