Treatment of hepatitis B e antigen positive chronic hepatitis with telbivudine or adefovir: a randomized trial

Ann Intern Med. 2007 Dec 4;147(11):745-54. doi: 10.7326/0003-4819-147-11-200712040-00183. Epub 2007 Oct 1.

Abstract

Background: The efficacy of nucleoside and nucleotide analogues for hepatitis B has been linked to the magnitude and durability of hepatitis B virus (HBV) suppression.

Objective: To compare the antiviral efficacy of telbivudine and adefovir dipivoxil, and the effects of switching from adefovir to telbivudine, in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B.

Design: Randomized, controlled, open-label trial.

Setting: 16 outpatient clinics.

Patients: 135 treatment-naive, HBeAg-positive adults with chronic hepatitis B.

Intervention: Patients were randomly assigned in a 1:1:1 ratio to 52 weeks of telbivudine (group A) or adefovir (group B), or 24 weeks of adefovir and then telbivudine for the remaining 28 weeks (group C). One hundred thirty-one patients completed 52 weeks of treatment.

Measurements: The primary efficacy comparison was serum HBV DNA reduction at week 24, with a secondary comparison at week 52.

Results: At week 24, mean HBV DNA reduction was greater in group A than in pooled groups B and C (-6.30 vs. -4.97 log10 copies/mL; difference, -1.33 log10 copies/mL [95% CI, -1.99 to -0.66 log(10) copies/mL]; P < 0.001), and more patients in group A were polymerase chain reaction-negative (39% vs. 12%; odds ratio, 4.46 [CI, 1.86 to 10.72]; P = 0.001). At week 52, the mean residual HBV DNA level was lower in group A and group C than in group B (3.01 log10 copies/mL [group A] and 3.02 log10 copies/mL [group C] vs. 4.00 log10 copies/mL [group B]; difference, -0.99 log10 copies/mL [CI, -1.67 to -0.32 log10 copies/mL] and -0.98 log10 copies/mL [CI, -1.64 to -0.32 log10 copies/mL]; P = 0.004). Adverse events were similar across groups; the most common were upper respiratory symptoms, headache, back pain, and diarrhea.

Limitations: The trial was open-label and was not of sufficient size or duration to compare clinical outcomes and long-term efficacy.

Conclusion: Telbivudine demonstrated greater and more consistent HBV DNA suppression than adefovir after 24 weeks of treatment. After 52 weeks, HBV DNA suppression was greater in patients who had received continuous telbivudine or were switched to telbivudine after 24 weeks than in those who received continuous adefovir.

Trial registration: ClinicalTrials.gov NCT00115245.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • DNA, Viral / blood
  • Drug Therapy, Combination
  • Female
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology*
  • Humans
  • Male
  • Middle Aged
  • Nucleosides / adverse effects
  • Nucleosides / therapeutic use*
  • Organophosphonates / adverse effects
  • Organophosphonates / therapeutic use*
  • Pyrimidinones / adverse effects
  • Pyrimidinones / therapeutic use*
  • Telbivudine
  • Thymidine / analogs & derivatives
  • Viral Load

Substances

  • Antiviral Agents
  • Biomarkers
  • DNA, Viral
  • Hepatitis B e Antigens
  • Nucleosides
  • Organophosphonates
  • Pyrimidinones
  • Telbivudine
  • Adenine
  • adefovir dipivoxil
  • Thymidine

Associated data

  • ClinicalTrials.gov/NCT00115245