title: Individualized treatment of HBeAg-negative chronic hepatitis B using pegylated interferon-α2a as first-line and week-12 HBV DNA/HBsAg stopping rule: a cost-effectiveness analysis.
abstract: BACKGROUND
  Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) is the most frequent and difficult-to-treat viral hepatitis worldwide. HBV DNA and hepatitis B surface antigen (HBsAg) serum levels, which help the early identification of non-responders to pegylated interferon (PEG-IFN), prompt more flexible individualized therapeutic strategies exploiting the benefits of both PEG-IFN and nucleoside/nucleotide analogues (NAs). We assessed the cost-effectiveness of week-12 HBV DNA/HBsAg stopping rule for early interruption and switch to currently most effective NA treatments (entecavir [ETV] or tenofovir disoproxil fumarate [TDF]).
  
  
  METHODS
  A decision-analytic Markov model was developed in the following health-related states: CHB, compensated cirrhosis (CC) and decompensated cirrhosis, hepatocellular carcinoma, liver transplant, post-liver transplant, death, virological response, relapse and HBsAg clearance. Simulated strategies included: ETV/TDF in CHB; ETV/TDF delayed until CC; first-line PEG-IFN followed by switch to ETV/TDF for either patients meeting the week-12 stopping rule or week-48 null-responders/relapsers; and first-line PEG-IFN followed by switch to ETV/TDF delayed until CC. ETV and TDF were considered alternatively for a total of eight strategies. A lifetime simulation horizon was applied.
  
  
  RESULTS
  Early treatment strategies using NAs with or without first-line PEG-IFN provided the highest results (approximately 22 life-years and 15 quality-adjusted life years [QALYs]). Delayed treatments until cirrhosis development resulted in poorer outcomes. The average per-patient lifetime costs ranged from €33,500 (TDF in CC) to €68,900 (TDF in CHB). Costs using ETV were 20-50% higher. First-line PEG-IFN strategies ranged from dominant (that is, more effective and less costly) to highly cost-effective, although differences in QALYs were always very narrow.
  
  
  CONCLUSIONS
  The cost-effectiveness of antiviral therapy of HBeAg-negative CHB could be improved significantly using first-line PEG-IFN followed by a switch to NAs in either patients meeting the week-12 HBV DNA/HBsAg stopping rule or week-48 non-responders/relapsers.
authors.affiliation: IMS Health Economics & Outcomes Research, Milan, Italy. siannazzo@it.imshealth.com.
authors.forename: Sergio
authors.initials: S
authors.lastname: Iannazzo
authors.forename: Barbara
authors.initials: B
authors.lastname: Coco
authors.forename: Maurizia R
authors.initials: MR
authors.lastname: Brunetto
authors.forename: Francesca
authors.initials: F
authors.lastname: Rossetti
authors.forename: Antonietta
authors.initials: A
authors.lastname: Caputo
authors.forename: Andrea
authors.initials: A
authors.lastname: Latour
authors.forename: Belen
authors.initials: B
authors.lastname: Espinos
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Bonino
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control; D003362:Cost-Benefit Analysis; D004334:Drug Administration Schedule; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; 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 / Q000175:diagnosis / Q000188:drug therapy / Q000191:economics* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000517:prevention & control; D008113:Liver Neoplasms / Q000517:prevention & control; D008297:Male; D008390:Markov Chains; D063065:Organophosphonates / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D057285:Precision Medicine; D011379:Prognosis; D019057:Quality-Adjusted Life Years; D011994:Recombinant Proteins / Q000627:therapeutic use; D000068698:Tenofovir; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D063065:Organophosphonates; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir; C417083:peginterferon alfa-2b; D000225:Adenine; C100416:peginterferon alfa-2a