title: Cost-Effectiveness Analysis of Alternative Antiviral Strategies for the Treatment of HBeAg-Positive and HBeAg-Negative Chronic Hepatitis B in the United Kingdom.
abstract: BACKGROUND
  Seven drugs are licensed for the treatment of chronic hepatitis B (CHB) in the United Kingdom. Which initial treatment, secondary therapy, and whether antivirals should be given alone or in combination are questions of considerable uncertainty.
  
  
  OBJECTIVE
  The aim of this model was to undertake a comprehensive economic evaluation of all antiviral treatments for CHB to recommend the most cost-effective therapeutic sequence.
  
  
  METHODS
  We developed a probabilistic Markov model to compare the cost-effectiveness of all clinically relevant antiviral treatment sequences for nucleos(t)ide-naive adults with hepatitis B e-antigen (HBeAg)-positive or HBeAg-negative CHB. Relative rates of HBeAg seroconversion and viral suppression were obtained from a network meta-analysis. Data on mortality, antiviral drug resistance, durability of response, adverse events, and costs were obtained from published literature. Results are reported in terms of lifetime costs, quality-adjusted life-years (QALYs), and expected net benefit.
  
  
  RESULTS
  In the base-case analysis, pegylated interferon alpha-2a (peg-IFN α-2a) followed by tenofovir disoproxil fumarate was most effective and cost-effective in HBeAg-positive patients, with a cost of £7488 per QALY gained compared with no treatment. In HBeAg-negative patients, peg-IFN α-2a followed by entecavir was most effective and cost-effective, with a cost of £6981 per QALY gained. The model was robust to a wide range of sensitivity analyses.
  
  
  CONCLUSIONS
  Peg-IFN α-2a followed by tenofovir disoproxil fumarate or entecavir is the most effective antiviral treatment strategy for people with both variants of CHB. At a cost of less than £10,000 per QALY gained, these sequences are considered cost-effective in England and Wales. The results of this analysis were used to inform 2013 National Institute for Health and Care Excellence guideline recommendations.
authors.affiliation: Symmetron Limited, Toronto, Ontario, Canada. Electronic address: s.l.bermingham@gmail.com.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Bermingham
authors.affiliation: Royal College of Physicians, National Clinical Guideline Centre, London, UK.
authors.forename: Ralph
authors.initials: R
authors.lastname: Hughes
authors.affiliation: Royal College of Physicians, National Clinical Guideline Centre, London, UK.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Fenu
authors.affiliation: Symmetron Limited, Borehamwood, UK.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Sawyer
authors.affiliation: Virology Laboratory, Health Protection Agency, Microbiology Services Division, Heartlands Hospital, Birmingham, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Boxall
authors.affiliation: Barts and The London School of Medicine and Dentistry, London, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: T Kennedy
authors.affiliation: UCL Institute of Liver and Digestive Health, Royal Free Hospital, London, UK.
authors.forename: Geoff
authors.initials: G
authors.lastname: Dusheiko
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity, Sydney School of Public Health, University of Sydney, Sydney, Australia.
authors.forename: Grant
authors.initials: G
authors.lastname: Hill-Cawthorne
authors.affiliation: Section of Hepatology and Gastroenterology, Department of Medicine, Imperial College, London, UK.
authors.forename: Howard
authors.initials: H
authors.lastname: Thomas
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000191:economics* / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D057186:Comparative Effectiveness Research; D003362:Cost-Benefit Analysis; D003661:Decision Support Techniques; D016527:Drug Costs; D057915:Drug Substitution / Q000191:economics; D004359:Drug Therapy, Combination / Q000191:economics; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics*; D006801:Humans; D008297:Male; D008390:Markov Chains; D018803:Models, Economic; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D011336:Probability; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D013222:State Medicine / Q000191:economics; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006513:Hepatitis B e Antigens
keywords: antiviral treatment; chronic hepatitis B; cost-effectiveness analysis; interferon-alpha; nucleosides; nucleotides