title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.forename: Deming
authors.initials: D
authors.lastname: Tan
authors.forename: Qin
authors.initials: Q
authors.lastname: Ning
authors.forename: Junqi
authors.initials: J
authors.lastname: Niu
authors.forename: Xuefan
authors.initials: X
authors.lastname: Bai
authors.forename: Rong
authors.initials: R
authors.lastname: Fan
authors.forename: Shijun
authors.initials: S
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yu
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Guangfeng
authors.initials: G
authors.lastname: Shi
authors.forename: Mobin
authors.initials: M
authors.lastname: Wan
authors.forename: Xinyue
authors.initials: X
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
authors.forename: Jifang
authors.initials: J
authors.lastname: Sheng
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Dou
authors.forename: Junping
authors.initials: J
authors.lastname: Shi
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.forename: Maorong
authors.initials: M
authors.lastname: Wang
authors.forename: Hongfei
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Gao
authors.forename: Chengwei
authors.initials: C
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Jidong
authors.initials: J
authors.lastname: Jia
authors.forename: Jinlin
authors.initials: J
authors.lastname: Hou
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D002681:China; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000077712:Telbivudine; D013936:Thymidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D000077712:Telbivudine; C053001:adefovir; D000410:Alanine Transaminase; D000225:Adenine; D013936:Thymidine