The 104-week efficacy and safety of telbivudine-based optimization strategy in chronic hepatitis B patients: A randomized, controlled study


  • Potential conflicts of interest: Q.N. has been a member of Advisory Committees or Review Panels, received consulting fees from Roche, Novartis, GlaxoSmithKline, Bristol-Myers Squibb and has received grant/research support from Roche, Novartis, and Bristol-Myers Squibb. X.G.D. has sat on advisory boards for Roche, Bristol-Myers Squibb, MSD, GlaxoSmithKline, and Novartis and received honoraria as a speaker for Roche, MSD, Bristol-Myers Squibb, GlaxoSmithKline, and Novartis. H.M. has received research grants from Roche, Novartis, Bristol-Myers Squibb, and GlaxoSmithKline and is on the speakers' bureau for Roche, Novartis, and Sanofi-Aventis. J.D.J. has acted as a consultant for Novartis, Bristol-Myers Squibb, GlaxoSmithKline, Roche, and MSD. J.L.H. has received consulting fees from Roche, Novartis, GlaxoSmithKline, Bristol-Myers Squibb and has received grant/research support from Roche, Novartis, and GlaxoSmithKline. The other authors declare that they have no conflicts of interest.

  • Funded by National Science and Technology Major Project (2012ZX10002003).


An optimization strategy based on the Roadmap concept is supposed to improve the clinical outcomes of patients with suboptimal antiviral response. The aim of this study was to prove the concept with a multicenter, open-label, randomized, controlled study. In all, 606 hepatitis B e antigen (HBeAg)-positive, nucleos(t)ide-naive chronic hepatitis B patients were randomized to the Optimize or Mono group. Patients in the Optimize group were treated with telbivudine for 24 weeks, after which those suboptimal responders with HBV DNA ≥300 copies/mL at week 24 received telbivudine plus adefovir until week 104, while the early virological responders continued telbivudine monotherapy. Patients in the Mono group received telbivudine monotherapy. All patients with telbivudine monotherapy had adefovir added if viral breakthrough developed. Sixty-eight percent (204/300) of patients in the Optimize group had adefovir added due to suboptimal response. At week 104, compared to the Mono group, more patients in the Optimize group achieved HBV DNA <300 copies/ml (76.7% versus 61.2%, P < 0.001) with less genotypic resistance (2.7% versus 25.8%, P < 0.001). The rates of HBeAg seroconversion and alanine aminotransferase (ALT) normalization were comparable between the two groups (23.7% versus 22.1%; 80.7% versus 79.2%). For week 24 suboptimal responders, telbivudine plus adefovir showed an additive antiviral potency, with 71.1% achieving virological response at week 104 and only 0.5% developing genotypic resistance, compared with 46.6% who achieved virological response and 37.8% who developed genotypic resistance with telbivudine monotherapy. Both treatment regimens were well tolerated, with an observed persistent increase of the glomerular filtration rate. Conclusion: For suboptimal virological responders to telbivudine at week 24, adjusting the treatment strategy is recommended. Adding adefovir can benefit these patients with additive antiviral potency and low resistance without increased side effects. (Hepatology 2014;59:1283-1292)