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

Abstract

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.

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  • Authors+Show Affiliations

    ,

    Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.

    , , , , , , , , , , , , , , , , , , , , , , , , ,

    Source

    Hepatology (Baltimore, Md.) 59:4 2014 Apr pg 1283-92

    MeSH

    Adenine
    Adolescent
    Adult
    Alanine Transaminase
    Antiviral Agents
    China
    Dose-Response Relationship, Drug
    Drug Therapy, Combination
    Female
    Glomerular Filtration Rate
    Hepatitis B e Antigens
    Hepatitis B, Chronic
    Humans
    Longitudinal Studies
    Male
    Middle Aged
    Organophosphonates
    Thymidine
    Time Factors
    Treatment Outcome
    Young Adult

    Pub Type(s)

    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24382690

    Citation

    TY - JOUR T1 - The 104-week efficacy and safety of telbivudine-based optimization strategy in chronic hepatitis B patients: a randomized, controlled study. AU - Sun,Jian, AU - Xie,Qing, AU - Tan,Deming, AU - Ning,Qin, AU - Niu,Junqi, AU - Bai,Xuefan, AU - Fan,Rong, AU - Chen,Shijun, AU - Cheng,Jun, AU - Yu,Yanyan, AU - Wang,Hao, AU - Xu,Min, AU - Shi,Guangfeng, AU - Wan,Mobin, AU - Chen,Xinyue, AU - Tang,Hong, AU - Sheng,Jifang, AU - Dou,Xiaoguang, AU - Shi,Junping, AU - Ren,Hong, AU - Wang,Maorong, AU - Zhang,Hongfei, AU - Gao,Zhiliang, AU - Chen,Chengwei, AU - Ma,Hong, AU - Jia,Jidong, AU - Hou,Jinlin, Y1 - 2014/02/28/ PY - 2013/7/12/received PY - 2013/10/4/accepted PY - 2014/2/28/aheadofprint PY - 2014/1/3/entrez PY - 2014/1/3/pubmed PY - 2014/6/10/medline SP - 1283 EP - 92 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 59 IS - 4 N2 - 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. SN - 1527-3350 UR - https://www.unboundmedicine.com/medline/citation/24382690/The_104_week_efficacy_and_safety_of_telbivudine_based_optimization_strategy_in_chronic_hepatitis_B_patients:_a_randomized_controlled_study_ L2 - http://dx.doi.org/10.1002/hep.26885 ER -