A randomized, controlled trial of combination therapy for chronic hepatitis B: comparing pegylated interferon-alpha2b and lamivudine with lamivudine alone.

Abstract

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 microg/kg of body weight per week; maximum, 100 microg) 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 log10 copies/mL vs. 2.83 log10 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 erythematous 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-alpha2b and lamivudine may lead to a higher rate of virologic response than lamivudine monotherapy.

• Authors: Henry Lik-Yuen Chan, Nancy Wai-Yee Leung, Alex Yui Hui, Vincent Wai-Sun Wong, Choong-Tsek Liew, Angel Mei-Ling Chim, Francis Ka-Leung Chan, Lawrence Cheung-Tsui Hung, Yuk-Tong Lee, John Siu-Lun Tam, Christopher Wai-Kei Lam, Joseph Jao-Yiu Sung
• Journal: Annals of internal medicine (Ann Intern Med) Vol. 142 Issue 4 Pg. 240-50 (Feb 15 2005) ISSN: 1539-3704 [Electronic] United States
• PMID: 15710957 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• DNA, Viral
• Hepatitis B e Antigens
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• Lamivudine
• Polyethylene Glycols
• Alanine Transaminase
• peginterferon alfa-2b

Topics

• Adolescent
• Adult
• Aged
• Alanine Transaminase (blood)
• Antiviral Agents (adverse effects, therapeutic use)
• DNA, Viral (blood)
• Drug Administration Schedule
• Drug Therapy, Combination
• Hepatitis B e Antigens (blood)
• Hepatitis B virus (physiology)
• Hepatitis B, Chronic (blood, drug therapy)
• Humans
• Interferon alpha-2
• Interferon-alpha (adverse effects, therapeutic use)
• Lamivudine (adverse effects, therapeutic use)
• Middle Aged
• Polyethylene Glycols
• Recombinant Proteins
• Viral Load