A randomized, controlled trial of combination therapy for chronic hepatitis B:: Comparing pegylated interferon-α2b and lamivudine with lamivudine alone

Background: conventional interferon and lamivudine monotherapy are unsatisfactory in treating hepatitis B virus (HBV) infection. Objective: To evaluate the efficacy and safety of pegylated interferon-alpha2b and lamivudine combination therapy for chronic hepatitis B. Design: Randomized, controlled, open-label trial. Setting: Outpatient clinic in a referral center. Participants: 100 treatment-naive patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B and moderately elevated alanine aminotransferase levels. Measurement: The primary end point was sustained virologic response (HBeAg seroconversion and HBV DNA level < 500 000 copies/mL) at 24 weeks after cessation of treatment. Intervention: A staggered regimen of combination therapy with pegylated interferon-alpha2b (1.5 mug/kg of body weight per week; maximum, 100 mug) given for 32 weeks plus lamivudine (100 mg daily) given for 52 weeks versus lamivudine (100 mg daily) monotherapy given for 52 weeks. Of the 100 participants, 96% completed treatment and 80% completed post-treatment follow-up. Results: The rate of sustained virologic response was 36% for the combination treatment group and 14% for the lamivudine monotherapy group (absolute difference, 22 percentage points [95% CI, 6 to 38 percentage points]). End-of-treatment outcomes showed that, compared with monotherapy, patients receiving combination therapy more often had virologic response (60% vs. 28% [absolute difference, 32 percentage points (CI, 14 to 50 percentage points)]); had more substantial reductions of HBV DNA (3.91 log(10) copies/mL vs. 2.83 log(10) copies/mL); and less often had lamivudine-resistant mutants (21% vs. 40%). The percentages of patients with normalization of alanine aminotransferase levels and histologic improvement did not differ. Adverse effects, such as transient influenza-like symptoms, alopecia, and local erythernatous reactions, were more common with combination therapy. Limitations: This study lacked a double-blind design and was conducted at 1 institution. Because of the staggered pegylated interferon-lamivudine regimen, patients assigned to combination therapy received treatment for 8 weeks longer than those assigned to monotherapy. Conclusions: In patients with HBeAg-positive chronic hepatitis B, staggered combination treatment with pegylated interferon-a2b and lamivudine may lead to a higher rate of virologic response than lamivudine monotherapy.