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

Abstract

UNLABELLED:

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.

• Authors: Jian Sun, Qing Xie, Deming Tan, Qin Ning, Junqi Niu, Xuefan Bai, Rong Fan, Shijun Chen, Jun Cheng, Yanyan Yu, Hao Wang, Min Xu, Guangfeng Shi, Mobin Wan, Xinyue Chen, Hong Tang, Jifang Sheng, Xiaoguang Dou, Junping Shi, Hong Ren, Maorong Wang, Hongfei Zhang, Zhiliang Gao, Chengwei Chen, Hong Ma, Jidong Jia, Jinlin Hou
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 59 Issue 4 Pg. 1283-92 (Apr 2014) ISSN: 1527-3350 [Electronic] United States
• PMID: 24382690 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by the American Association for the Study of Liver Diseases.

Chemical References

• Antiviral Agents
• Hepatitis B e Antigens
• Organophosphonates
• Telbivudine
• adefovir
• Alanine Transaminase
• Adenine
• Thymidine

Topics

• Adenine (adverse effects, analogs & derivatives, pharmacology, therapeutic use)
• Adolescent
• Adult
• Alanine Transaminase (blood)
• Antiviral Agents (adverse effects, pharmacology, therapeutic use)
• China
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Female
• Glomerular Filtration Rate (drug effects)
• Hepatitis B e Antigens (blood)
• Hepatitis B, Chronic (blood, drug therapy)
• Humans
• Longitudinal Studies
• Male
• Middle Aged
• Organophosphonates (adverse effects, pharmacology, therapeutic use)
• Telbivudine
• Thymidine (adverse effects, analogs & derivatives, pharmacology, therapeutic use)
• Time Factors
• Treatment Outcome
• Young Adult