Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B.

Abstract

BACKGROUND:

Available treatments for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B are associated with poor sustained responses. As a result, nucleoside and nucleotide analogues are typically continued indefinitely, a strategy associated with the risk of resistance and unknown long-term safety implications.

METHODS:

We compared the efficacy and safety of peginterferon alfa-2a (180 microg once weekly) plus placebo, peginterferon alfa-2a plus lamivudine (100 mg daily), and lamivudine alone in 177, 179, and 181 patients with HBeAg-negative chronic hepatitis B, respectively. Patients were treated for 48 weeks and followed for an additional 24 weeks.

RESULTS:

After 24 weeks of follow-up, the percentage of patients with normalization of alanine aminotransferase levels or hepatitis B virus (HBV) DNA levels below 20,000 copies per milliliter was significantly higher with peginterferon alfa-2a monotherapy (59 percent and 43 percent, respectively) and peginterferon alfa-2a plus lamivudine (60 percent and 44 percent) than with lamivudine monotherapy (44 percent, P=0.004 and P=0.003, respectively; and 29 percent, P=0.007 and P=0.003, respectively). Rates of sustained suppression of HBV DNA to below 400 copies per milliliter were 19 percent with peginterferon alfa-2a monotherapy, 20 percent with combination therapy, and 7 percent with lamivudine alone (P<0.001 for both comparisons with lamivudine alone). Loss of hepatitis B surface antigen occurred in 12 patients in the peginterferon groups, as compared with 0 patients in the group given lamivudine alone. Adverse events, including pyrexia, fatigue, myalgia, and headache, were less frequent with lamivudine monotherapy than with peginterferon alfa-2a monotherapy or combination therapy.

CONCLUSIONS:

Patients with HBeAg-negative chronic hepatitis B had significantly higher rates of response, sustained for 24 weeks after the cessation of therapy, with peginterferon alfa-2a than with lamivudine. The addition of lamivudine to peginterferon alfa-2a did not improve post-therapy response rates.

• Authors: Patrick Marcellin, George K K Lau, Ferruccio Bonino, Patrizia Farci, Stephanos Hadziyannis, Rui Jin, Zhi-Meng Lu, Teerha Piratvisuth, Georgios Germanidis, Cihan Yurdaydin, Moises Diago, Selim Gurel, Ming-Yang Lai, Peter Button, Nigel Pluck, Peginterferon Alfa-2a HBeAg-Negative Chronic Hepatitis B Study Group
• Journal: The New England journal of medicine (N Engl J Med) Vol. 351 Issue 12 Pg. 1206-17 (Sep 16 2004) ISSN: 1533-4406 [Electronic] United States
• PMID: 15371578 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2004 Massachusetts Medical Society

Chemical References

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

Topics

• Adolescent
• Adult
• Aged
• Alanine Transaminase (blood)
• Antiviral Agents (adverse effects, therapeutic use)
• DNA, Viral (blood)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Hepatitis B e Antigens (blood)
• Hepatitis B virus (drug effects, genetics)
• Hepatitis B, Chronic (blood, drug therapy, virology)
• Humans
• Interferon alpha-2
• Interferon-alpha (adverse effects, therapeutic use)
• Lamivudine (adverse effects, therapeutic use)
• Male
• Middle Aged
• Polyethylene Glycols (adverse effects, therapeutic use)
• Recombinant Proteins