No Clear Predictors of Sustained Response to Peginterferon Alfa-2a (Pegasys) for HBeAg-negative Chronic Hepatitis B

Prior studies indicate that In patients with HBeAg-negative chronic hepatitis B (CHB), peginterferon alfa-2a (Pegasys) alone or combined with lamivudine (Epivir-HBV) provides significantly higher response rates 24 weeks post-treatment compared with lamivudine alone.

Study results indicate that age, baseline ALT and baseline HBV DNA are significant predictors of virologic response (HBV DNA <20,000 copies/ml) to peginterferon alfa-2a when assessed 24 weeks post-treatment.

In the current study, investigators sought to evaluate factors associated with sustained virologic response (defined as 48 weeks post-treatment response) to peginterferon alfa-2a monotherapy.

HBeAg-negative patients (n=177) were treated for 48 weeks with 180 mg peginterferon alfa-2a (40KD) (Pegasys) once-weekly. HBV DNA was measured regularly during the 48 week post-treatment follow-up period (weeks 48, 52, 56, 60, 64, 72, 84 and 96).

Analyses performed to identify baseline and on-treatment factors associated with post-treatment virologic response included the following variables: gender; race; age; bodyweight; baseline ALT; baseline HBV DNA; end of treatment HBV DNA; and HBV genotype.

Results

• Of 144 patients who had a virologic response (<20,000 copies/ml) to peginterferon alfa-2a monotherapy at the end of treatment, 89 had available data 48 weeks post-treatment.
• Of these patients, 49 (55%) sustained HBV DNA levels <100,000 cp/mL during the 48 week follow-up period.
• Patients with sustained virologic response had higher mean ALT levels at baseline (94.7 IU/L) compared with patients with relapse (77.6 IU/L).
• Mean baseline HBV DNA levels were 7.18 and 6.99 log for sustained responders and relapsers, respectively.
• HBV DNA level at the end of treatment was not different in patients with sustained response and those with relapse (2.5 and 2.6 log, respectively).
• The rate of sustained virologic response according to HBV genotype was 60% [3/5], 43% [12/28], 64% [27/42] and 50% [5/10] for genotypes A, B, C and D, respectively (P=0.08 for comparison of genotype B vs C).

In patients with HBeAg-negative CHB, a finite 48-week course of peginterferon alfa-2a was able to induce virologic response that was sustained 48 weeks post-treatment in more than half of the patients.

In conclusion, the authors write, “There was no clear predictor of sustained response to peginterferon alfa-2a. However, there was a trend toward better response in patients with high ALT at baseline or who were infected with HBV genotype C.”

“Baseline or end-of-treatment HBV DNA levels were not indicative of sustained virologic response.”

11/28/05

Reference
P Marcellin and others. Factors associated with sustained virologic response 1 year after treatment with peginterferon alfa-2a (40KD) (PEGASYS®) monotherapy for HBeAg-negative chronic hepatitis B. Abstract 976. Abstracts of the 56^th annual meeting of the American Association for the Study of Liver Diseases. November 11-15, 2005. San Francisco, CA.