| Emtricitabine Shows Potent Activity When Administered Once Daily for Treatment of Chronic Hepatitis B
The current study was a randomized, double blind, placebo controlled trial to assess the safety and efficacy of emtricitabine/ FTC in the treatment of chronic HBV. FTC is a cytidine analog that selectively inhibits the HBV DNA polymerase. Emtricitabine (Emtriva) is FDA-approved for the treatment of HIV infection in combination with other antiretrovirals.
All patients were HBsAg positive, HBeAg positive or negative and HBV DNA positive, had elevated serum ALT within 3 months of enrollment and a necroinflammatory score of >3 (Knodell HAI) on liver biopsy (LBX).
Patients were randomized (2:1) to receive either FTC 200 mg QD or placebo for 48 weeks at which time the LBX was repeated. HBV DNA was assessed by the Digene assay (lower limit of detection (LLD) 4700 copies/mL). Patients with detectable HBV DNA at week 48 were typed for presence of YMDD mutation.
The primary efficacy parameter was histological response; defined as a reduction of at least two points in the Knodell necroinflammatory score and lack of fibrosis progression.
The primary safety parameter was failure to tolerate study medication.
Secondary endpoints included virologic, serologic and, biochemical responses and emergence of drug resistant mutations.
Results
The study population consisted of 248 patients with mean age of 40 yrs, 71% male, 59% Asian and 38% Caucasian; 63% were HBeAg positive.
After 48 weeks of treatment, serum ALT was normal in 65% vs 25% of FTC and placebo treated patients (p<0.001) and HBV DNA was undetectable in 56% vs 7% (p<0.001) respectively. 43% of patients treated with FTC had both normal ALT and undetectable HBV DNA vs 4% in the placebo group (p<0.001).
Similar results were observed in both HBeAg positive and negative patients. 12% of HBeAg positive patients seroconverted and became HBeAg negative and anti-HBe positive. This was similar in both FTC and placebo groups.
After 48 weeks, 12.6% of FTC treated patients developed YMDD mutation. Histologic response was observed in 62% vs 25% of FTC and placebo patients respectively (p<0.001).
When analyzed by ranked assessment FTC treated patients had a greater improvement in both necroinflammatory activity (p<0.001) and fibrosis (p<0.009) compared to patients treated with placebo. 3% percent of patients discontinued study drug due to adverse events.
The most common AEs observed were upper respiratory infection, abdominal pain, fatigue, influenza and headache. These were observed in similar frequency in both the FTC and placebo treatment groups.
Conclusion
The authors conclude, 揊TC at a dose of 200 mg QD produced significant histologic improvement, with both a reduction of inflammation and fibrosis when compared to placebo after 48 weeks of treatment in both HBeAg positive and HBeAg negative chronic HBV patients.?/span>
揊TC demonstrated potent antiviral activity and had a safety and tolerability profile similar to placebo during treatment.?/span>
11/08/04 Reference
M L Shiffman and others. A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF EMTRICITABINE (FTC, EMTRIVA) ADMINISTERED ONCE-DAILY FOR TREATMENT OF CHRONIC HEPATITIS B VIRUS (HBV) INFECTION. Abstract 22 (oral). 55th AASLD. October 29-November 2, 2004. Boston, MA.
[此贴子已经被作者于2004-11-8 13:20:09编辑过] | 
发表于 2004-11-9 03:20
