Real-world application of the roadmap model in chronic hepatitis B patients with telbivudine therapy.
BACKGROUND
The roadmap concept provides a strategy to maximize hepatitis B virus suppression and minimize drug resistance by add-on or switching therapy in patients with a suboptimal response at Week 24. The efficacy of this strategy in routine clinical practice remains to be validated.


OBJECTIVE
The aim of our study was to validate the roadmap concept in the treatment of chronic hepatitis B, and to investigate the virologic efficacy and kinetics of quantitative hepatitis B surface antigen (qHBsAg) during telbivudine therapy in a real-world setting.


METHODS
A prospective, cohort study enrolled 96 consecutive, treatment-naïve patients with chronic hepatitis B receiving telbivudine therapy. At Week 24, only 17 of 42 (40%) partial or inadequate responders (hepatitis B virus DNA 60-2000 and >2000 IU/mL, respectively) followed the roadmap model and consented to adefovir add-on therapy. The remaining patients continued to receive telbivudine monotherapy.


RESULTS
At Week 96, none of the patients receiving adefovir add-on therapy, and 28% of patients receiving telbivudine monotherapy, either partial or inadequate responders, developed genotypic resistance (P = 0.03). Poor early qHBsAg kinetics (an increase in qHBsAg >0.4 log IU/mL at Week 12) was the only significant predictor of genotypic resistance (adjusted hazard ratio = 13.83; 95% CI, 1.79-106.76; P = 0.01). Telbivudine monotherapy was efficacious in 94% of partial responders who did not have poor early qHBsAg kinetics, remaining free of drug resistance after 2 years.


CONCLUSIONS
The application of the roadmap model with add-on adefovir therapy prevented genotypic resistance. However, telbivudine monotherapy achieved a good response in the majority of partial responders who did not have poor early qHBsAg kinetics. Poor early qHBsAg kinetics was an early predictor of genotypic resistance at Week 96. Modification of the roadmap model to incorporate early qHBsAg kinetics may further optimize the efficacy of the treatment strategy of hepatitis B virus.
Division of Gastroenterology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, Republic of China; Department of Nursing, Meiho Institute of Technology, Ping-Tung, Taiwan, Republic of China.
Hsien-Chung
HC
Yu
Kung-Hung
KH
Lin
Ping-I
PI
Hsu
Feng-Woei
FW
Tsay
Huay-Min
HM
Wang
Tzung-Jiun
TJ
Tsai
Kwok-Hung
KH
Lai
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D011446:Prospective Studies; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D000077712:Telbivudine; C053001:adefovir; D000225:Adenine; D013936:Thymidine
add-on therapy; hepatitis B virus; quantitative hepatitis B surface antigen; roadmap concept; telbivudine