| Entecavir Is Superior to Lamivudine for Treatment of HBeAg (+) Chronic Hepatitis B in Nucleoside-na飗e Patients
Entecavir (ETV) is a potent and selective inhibitor of hepatitis B virus (HBV) polymerase. This Phase III trial compared the efficacy and safety of treatment with ETV 0.5 mg QD to treatment with lamivudine (LVD) 100 mg QD for 48 weeks in nucleoside-na飗e (< 12 weeks of prior nucleoside therapy), HBeAg (+) chronic hepatitis B patients.
ETV-022 is a multinational, double-blind, comparative Phase III trial in which 715 patients were randomized 1:1 to receive ETV 0.5 mg QD or LVD 100 mg QD. Eligible patients were HBeAg(+) and had HBV DNA > 3 MEq/mL by bDNA assay, ALT 1.3 −10 x ULN, and compensated liver function.
The primary endpoint, Histologic Improvement, was the proportion of patients having a > 2-point decrease in the Knodell necroinflammatory score and no worsening of fibrosis (worsening: > 1-point increase in Knodell fibrosis score).
Results
Mean baseline viral loads by PCR were ETV: 9.61 log10 c/mL; LVD: 9.69 log10 c/mL. Mean baseline ALTs were ETV: 141 U/L; LVD: 146 U/L. Results of primary and major secondary endpoints are listed below: Primary and Major Secondary Endpoints, Week 48 (non-completer = failure)
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At Week 48, HBeAg seroconversion (loss of HBeAg and gain of HBeAb) occurred in 21% of ETV and 18% of LVD patients. A greater proportion of LVD than ETV patients were observed to have virologic non-response (HBV DNA > 0.7 MEq/mL) at Week 48, and met protocol criteria to discontinue study treatment.
No mutations associated with resistance to ETV were detected. Safety was comparable between the two groups: 7% of patients in both groups had serious adverse events.
Conclusion
The authors conclude, 揈ntecavir achieves superior histologic, virologic, and biochemical improvement in HBeAg(+) chronic hepatitis B patients, with a comparable safety profile to LVD. Primary treatment with entecavir provided superior benefit over LVD in nucleoside-na飗e, HBeAg(+) chronic hepatitis B patients.?/span>
Commentary
揚reventing the progression of liver disease is the primary objective when treating chronic hepatitis B patients,?said Dr. Robert Gish, an AI463-022 study investigator and medical director of the California Pacific Medical Center抯 liver transplant program in San Francisco. 揚hase III data for entecavir have demonstrated that hepatitis B e-antigen positive patients receiving entecavir experienced statistically significant improvements in liver histology and viral suppression compared to lamivudine.?/span>
11/03/04
Reference
T T Chang and others (the BEHoLD Study Group). ENTECAVIR IS SUPERIOR TO LAMIVUDINE FOR THE TREATMENT OF HBEAG(+) CHRONIC HEPATITIS B: RESULTS OF PHASE III STUDY ETV-022 IN NUCLEOSIDE-NA颲E PATIENTS. Abstract 70 (poster). 55th AASLD. October 29-November 2, 2004. Boston, MA.
[此贴子已经被作者于2004-11-4 10:37:57编辑过] | 
发表于 2004-11-5 00:37
