Published online Nov 18, 2016. doi: 10.4254/wjh.v8.i32.1402
Peer-review started: March 18, 2016
First decision: April 19, 2016
Revised: May 6, 2016
Accepted: July 14, 2016
Article in press: July 18, 2016
Published online: November 18, 2016
To make efficacy and safety comparison of telbivudine-raodmap and tenofovir-roadmap in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients.
This was the first prospective, randomised, two-arm, open-label, non-inferiority study in HBeAg-negative CHB patients that compared telbivudine and tenofovir administered as per roadmap concept. Patients were treated up to 24 wk and, depending on virologic response, continued the same therapy or received add-on therapy up to 104 wk. Eligible patients received an additional 52 wk of treatment in the extension period (i.e., up to 156 wk). Patients who developed virologic breakthrough (VB) while on monotherapy also received add-on therapy. The primary efficacy endpoint was the rate of patients achieving hepatitis B virus (HBV) DNA < 300 copies/mL at week 52. Secondary efficacy endpoints included the rates of HBV DNA < 300 and < 169 copies/mL, HBV DNA change from baseline, alanine aminotransferase normalisation, hepatitis B surface antigen (HBsAg) loss, HBsAg seroconversion, VB, and emergence of resistance at various timepoints throughout the study. Safety and estimated glomerular filtration rate (eGFR) were also analysed.
A total of 241 patients were randomised. Non-inferiority of telbivudine arm to tenofovir arm was demonstrated at week 52 (± 7 d window), with over 91% of patients in each treatment arm achieving HBV DNA level < 300 copies/mL. Both arms were similar in terms of key secondary efficacy variables at weeks 104 and 156. The percentage of patients achieving HBV DNA < 300 copies/mL remained high and was similar in the telbivudine and tenofovir arms at both weeks 104 and 156. Over 82% of patients in both arms achieved alanine aminotransferase normalisation at week 52, and this percentage remained high at weeks 104 and 156. Telbivudine treatment progressively reduced serum HBsAg levels from baseline while no change was reported in quantitative HBsAg during therapy with tenofovir. Both treaments showed acceptable safety profiles. The telbivudine arm showed eGFR improvement unlike the tenofovir arm.
Efficacy was shown for both telbivudine-roadmap and tenofovir-roadmap regimens in HBeAg-negative CHB patients over 156 wk. Telbivudine arm was associated with renal improvement.
Core tip: This was the first prospective, randomised, non-inferiority study in hepatitis B e antigen-negative chronic hepatitis B patients that compared telbivudine and tenofovir administered as per roadmap concept. Both treatments based on the roadmap approach were effective over a 156 wk treatment period. Non-inferiority of telbivudine arm to tenofovir arm was demonstrated at week 52, with over 91% of patients in each treatment arm achieving hepatitis B virus DNA level < 300 copies/mL. Both treaments showed acceptable safety profiles. Moreover, telbivudine showed an improvement in estimated glomerular filtration rate from baseline.