Increasing Serologic, Virologic and Biochemical Response Over Time To Adefovir Dipivoxil (ADV) 10 mg in HBeAg+ Chronic Hepatitis B Patients
Adefovir dipivoxil/ ADV (Hepsera) has potent activity against wild-type and lamivudine-resistant HBV.?Treatment with ADV 10 mg over 48 wks demonstrated significant histological, virological, serological and biochemical improvement compared to placebo (PLB) in CHB.
Eligibility for participation in this trial included HBsAg+ ≥ 6 months, HBeAg+, serum HBV DNA ≥106 c/mL (Roche Amplicor?Monitor PCR, LLQ 1,000 c/mL) and ALT 1.2-10 x ULN.?Prior interferon was allowed, if > 6 months prior to enrollment.?
Patients (pts) were randomized to receive ADV 10 mg. 30 mg, or PLB.?
The study continued to evaluate the long term safety and efficacy of ADV 10 mg in pts who received ADV 10 mg in the first 48 wks.
At?DDW 2005, results were reported up to 144 wks. Most pts had ≥ 1 dose PLB in year 2 due to a dosing mis-allocation error.?As length of study follow-up varies, K-M* estimates were used.
Results
?span style='font:7.0pt "Times New Roman"'> 309 pts received ≥ 1 dose ADV 10 mg;
?span style='font:7.0pt "Times New Roman"'> 171 patients were eligible to continue open-label ADV up to 5 years.
?span style='font:7.0pt "Times New Roman"'> Baseline (BL) characteristics (n=309) were 74% male, 57% Asian and 38% Caucasian; the median age 34 years.?
?span style='font:7.0pt "Times New Roman"'> Baseline median serum HBV DNA was 8.11 log10 c/mL; median ALT was 85 IU/L (2.1 x ULN).
Baseline Week 48Week 96Week 144
% Serum? HBV DNA Undetectable by PCR (<1000 copies/mL)* 28%45%56%
% HBeAg seroconversion* 12%29%43%
% HBeAg loss* 21%42%51%
% ALT normalization* 58%71%81%
Note: Pts with confirmed HBeAg seroconversion or HBeAg loss were followed off-treatment
* Kaplan-Meier analysis
?span style='font:7.0pt "Times New Roman"'> ADV was generally well-tolerated through 144 wks.
?span style='font:7.0pt "Times New Roman"'> No pt had a confirmed serum creatinine increase from BL of ≥ 0.5 mg/dL or a serum phosphorus < 1.5 mg/dL.?
?span style='font:7.0pt "Times New Roman"'> No pt developed resistance by 48 wks; 2 patients (3.1%) developed resistance (1 N236T, 1 A181V) through 144 wks.
?span style='font:7.0pt "Times New Roman"'> HBeAg seroconversion was durable off therapy (median follow-up 55 weeks) in 91% of patients.
Conclusions?
In conclusion, the authors note
?span style='font:7.0pt "Times New Roman"'> Treatment with ADV 10 mg over 144 wks resulted in increasing clinical benefit, HBeAg loss and seroconversion.?
?span style='font:7.0pt "Times New Roman"'> HBeAg seroconversion was durable off therapy.
?span style='font:7.0pt "Times New Roman"'> Continued reductions in serum HBV DNA and ALT levels were demonstrated with increasing proportions of patients achieving undetectable serum HBV DNA and ALT normalization.?/span>
05/23/05
Reference
P Marcellin and others. [Abstract M931]
Increasing Serologic, Virologic and Biochemical Response Over Time To Adefovir Dipivoxil (ADV) 10 mg in HBeAg+ Chronic Hepatitis (CHB) Patients. Digestive Disease Week 2005. May 14-18, 2005. Chicago, IL. | 
发表于 2005-5-31 03:15
