A Randomized, Controlled Trial of Combination Therapy for Chronic Hepatitis B: Comparing Pegylated Interferon-α2b and Lamivudine with Lamivudine Alone
- Henry Lik-Yuen Chan, MD;
- Nancy Wai-Yee Leung, MD;
- Alex Yui Hui, MB, BChir;
- Vincent Wai-Sun Wong, MBChB;
- Choong-Tsek Liew, MD;
- Angel Mei-Ling Chim, BSc;
- Francis Ka-Leung Chan, MD;
- Lawrence Cheung-Tsui Hung, MB, BChir;
- Yuk-Tong Lee, MD;
- John Siu-Lun Tam, PhD;
- Christopher Wai-Kei Lam, PhD; and
- Joseph Jao-Yiu Sung, MD, PhD
- From the Chinese University of Hong Kong and Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China.
Abstract
Background: Conventional interferon and lamivudine monotherapy are unsatisfactory in treating hepatitis B virus (HBV) infection.
Objective: To evaluate the efficacy and safety of pegylatedinterferon-α2b 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-α2b (1.5 µg/kg of body weight per week; maximum, 100 µg) 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-α2b and lamivudine may lead to a higher rate of virologic response than lamivudine monotherapy.
Article and Author Information
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Grant Support: Schering-Plough Corp. supplied pegylated interferon-α2b, and GlaxoSmithKline supplied lamivudine.
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Potential Financial Conflicts of Interest: None disclosed.
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Requests for Single Reprints: Joseph J.-Y. Sung, MD, PhD, Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30–32 Ngan Shing Street, Shatin, Hong Kong SAR, China; e-mail, joesung{at}cuhk.edu.hk.
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Current Authors Addresses: Drs. H.L.-Y. Chan, F.K.-L. Chan, Lee, and Sung; Mr. Hui; Mr. Wong; Ms. Chim; and Mr. Hung: Departments of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30–32 Ngan Shing Street, Shatin, Hong Kong SAR, China.
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Dr. Leung: Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, 11 Chuen On Road, Tai Po, Hong Kong SAR, Hong Kong.
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Dr. Liew: Department of Anatomical and Cellular Pathology, 1/F Prince of Wales Hospital, 30–32 Ngan Shing Street, Shatin, Hong Kong SAR, China.
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Dr. Tam: Department of Microbiology, 1/F Prince of Wales Hospital, 30–32 Ngan Shing Street, Shatin, Hong Kong SAR, China.
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Dr. Lam: Department of Chemical Pathology, 1/F Prince of Wales Hospital, 30–32 Ngan Shing Street, Shatin, Hong Kong SAR, China.
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Author Contributions: Conception and design: H.L.-Y. Chan, J.J.-Y. Sung.
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Analysis and interpretation of the data: H.L.-Y. Chan, J.J.-Y. Sung.
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Drafting of the article: H.L.-Y. Chan.
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Critical revision of the article for important intellectual content: H.L.-Y. Chan, J.J.-Y. Sung.
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Final approval of the article: H.L.-Y. Chan, J.J.-Y. Sung.
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Provision of study materials or patients: H.L.-Y. Chan, N.W.-Y. Leung, A.Y. Hui, V.W.-S. Wong, F.K.-L. Chan, L.C.-T. Hung, Y.-T. Lee.
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Statistical expertise: H.L.-Y. Chan.
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Obtaining of funding: C.-T. Liew, J.J.-Y. Sung.
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Administrative, technical, or logistic support: A.M.-L. Chim, J.S.-L. Tam, C.W.-K. Lam, J.J.-Y. Sung.
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Collection and assembly of data: A.M.-L. Chim.
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