A MULTICENTER, OPEN-LABEL STUDY OF EFFICACY AND SAFETY OF PEGINTERFERON ALFA-2A (40KD) IN KOREAN PATIENTS WITH HBEAG-POSITIVE CHB HARBORING LAMIVUDINE-RESISTANT YMDD MUTANTS

Abstract

Background: Patients who are harboring HBV strains with YMDD resistance mutations following treatment with lamivudine represent an important target group for therapy. Treatment with newer antivirals such as entecavir is a problem, due to cross-resistance. These patients may benefit from an alternate interferon-based therapy.

Objectives: To evaluate the efficacy and safety of peginterferon alfa-2a (40KD) in Korean patients with HBeAg-positive CHB who have developed genotypic resistance to lamivudine. Korean patients are typically infected with HBV genotype C.

Methods: This was a non-randomized, open-label study conducted at various study centers in Korea. Patients were stratified as ‘naïve’ patients, who had not received any antiviral therapy for CHB within 6 months before enrollment (GroupA) or ‘YMDD mutant’ patients who had or were currently receiving lamivudine and who had genotypic evidence of YMDD mutations (Group B). All patients received 48 weeks of treatment with 180 μg peginterferon alfa-2a (40KD). Patients in Group B who were currently on lamivudine therapy received overlapping peginterferon alfa-2a (40KD) treatment with lamivudine for 12 weeks. Primary endpoints were HBV DNA<100,000 copies/mL (measured using Roche TAQMAN assay)and HBeAg seroconversion assessed 24 weeks after end of treatment.

Results: Among the 150 patients enrolled, 104 have completed treatment as planned at the time of analysis. Rates of HBV DNA suppression to <100,000 copies/mL were similar(26.2% for group A and 25.6% for group B). The overall HBeAg seroconversion rate was 27% and there was no significant difference in HBeAg seroconversion rates between the two groups: 26.2% (16/61) for group A and 27.9% (13/43) for group B. Thus far, 1 patient in group A has cleared HBsAg. Overall 39% of patients had normalized ALT levels (44.3% for group A and 32.6% for group B). The adverse event profiles were similar for the two groups; adverse events were those known to be associated with interferon-based therapy.

Conclusions: Patients who developed with lamivudine resistance can be treated effectively with peginterferon alfa-2a (40KD) with HBeAg seroconversion rate of 27.9%. This therapeutic approach is safe and results in an HBeAg seroconversion rate similar to that seen in lamivudine-naïve patients.