Treatment of Hepatitis B e Antigen-Positive Chronic Hepatitis with Telbivudine or Adefovir: A Randomized Trial.

Author(s): Chan HL, Heathcote EJ, Marcellin P, Lai CL, Cho M, Moon YM, Chao YC, Myers RP, Minuk GY, Jeffers L, Sievert W, Bzowej N, Harb G, Kaiser R, Qiao XJ, Brown NA, and the 018 Study Group*

Affiliation(s): The Chinese University of Hong Kong, Hong Kong, China; University of Toronto, Toronto, Ontario, Canada; Hopital Beaujon, Clichy, France; Pusan National University Hospital, Busan, Korea; Severance Hospital, Seoul, Korea; Tri-Service General Hospital, Taipei, Taiwan; University of Calgary, Calgary, Alberta, Canada; University of Manitoba, Winnipeg, Manitoba, Canada; University of Miami, Miami, Florida; Monash University, Melbourne, Victoria, Australia; California Pacific Medical Center, San Francisco, California; Novartis Pharmaceuticals, East Hanover, New Jersey; and Idenix Pharmaceuticals, Cambridge, Massachusetts.

Publication date & source: 2007-10-01, Ann Intern Med., [Epub ahead of print]

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 telbivudine (group A), 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 log(10) copies/mL; difference, -1.33 log(10) 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, mean residual HBV DNA was lower in patients treated continuously with (group A) or switched (group C) to telbivudine than in those who received continuous adefovir (group B) (3.01 log(10) copies/mL [group A] and 3.02 log(10) copies/mL [group C] vs. 4.00 log(10) copies/mL [group B]; difference, -0.99 log(10) copies/mL [CI, -1.67 to -0.32 log(10) copies/mL] and -0.98 log(10) copies/mL [CI, -1.64 to -0.32 log(10) 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. CONCLUSIONS: 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. *For members of the 018 Study Group, see the Appendix. ClinicalTrials.gov registration number: NCT00115245.