DDW 2008: Pegylated Interferon (Pegasys) Continues to Suppress HBV, Adding Adefovir (Hepsera) Provides No Extra Benefit

Several nucleoside/nucleotide analogs are approved for the treatment of chronic hepatitis B virus (HBV) infection, but their long-term effectiveness is limited by the emergence of drug-resistant virus. Another approved hepatitis B therapy,pegylated interferon, works by modulating the immune response against the virus.

 

The multicenter Italian PEG for B study compared the safety and efficacy of pegylated interferon monotherapy vs pegylated interferon plus the nucleotide analog adefovir (Hepsera). The trial included 60 participants (67% men; median age 48 years) with chronic hepatitis B "e" antigen (HBeAg) negative infection.

All patients had HBV DNA viral loads of 104 copies/mL or greater, elevated alanineaminotransferase (ALT) levels, and compensated liver disease. The mean baseline HBV DNA level was 6.4 log copies/mL and the mean ALT level was 3.3 times the upper limit of normal. Individuals with hepatitis C virus (HCV) or HIV coinfection, as well as those with clinical signs of cirrhosis, were not included.

Participants were randomly assigned (1:1) to receive 180 mcg/week pegylated interferonalfa-2a (Pegasys) monotherapy or pegylated interferon plus 10 mg adefovir for 48 weeks, followed by 24 weeks of post-treatment observation. Baseline characteristics were comparable in both groups.

The primary study endpoint was sustained virological response (SVR), defined as serumHBV DNA < 104 copies/mL at the end of the post-treatment observation period.

Preliminary 24-week data from the study were presented at the European Association for the Study of the Liver (EASL) annual meeting in April 2007. More recently, at the Digestive Disease Week 2008 conference last month in San Diego, Paola Piccolo and colleagues presented longer-term, 48-week outcomes.

Results

• After 48 weeks of antiviral treatment, 69% of patients in the combination therapy group had undetectable HBV DNA, compared with 32% in thepegylated interferon monotherapy group (P < 0.01).

• ALT normalization occurred in 55% and 25%, respectively (P < 0.05). 

• At the end of post-treatment follow-up, about 80% of patients in both groups experienced virological relapse.

• 21% in the combination therapy group and 18% in the monotherapy group achieved SVR (not a significant difference).

• Mean post-treatment serum HBV DNA levels were about 5 log copies/mL in both groups.

• Post-treatment ALT levels increased to about 4 times the upper limit of normal in both groups.

• 1 patient in the combination therapy group, but none in the monotherapy arm, achieved hepatitis B surface antigen (HBsAg) loss. 

• In a multiple regression analysis, SVR was associated with a lower baseline fibrosis score. 

• 13% of participants in both groups discontinued therapy early due to adverse events. 

• Nearly 25% required pegylated interferon dose reduction to manage side effects.

"In HBeAg negative chronic hepatitis B, combination pegylated interferon plus adefovir treatment for 48 weeks is safe, and results in greater serum HBV DNA suppression and ALT normalization than pegylated interferon monotherapy," the study investigators concluded.

However, they added, "after 24 weeks of follow-up there is no difference in SVR and ALT levels between the two treatment regimens."

6/03/08

Reference

P Piccolo, L De Melia, F Bandiera, and others. Peginterferon alpha-2a plus adefovir dipivoxil vs. peginterferon alpha-2a monotherapy for 48 weeks in HBeAg-negative chronic hepatitis B: final results of the PEG for B randomized multicenter trial. Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22, 2008. Abstract 256.

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