title: Cost effectiveness of entecavir versus lamivudine with adefovir salvage in HBeAg-positive chronic hepatitis B.
abstract: OBJECTIVE
  To evaluate the cost effectiveness of treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with entecavir compared with lamivudine with adefovir salvage, based primarily on the results of a recent 2-year, randomised, multicentre, clinical trial (n = 709). Previous economic analyses have been limited by the lack of comparative clinical data for entecavir and lamivudine beyond 1-year duration and for salvage therapy.
  
  
  METHODS
  We conducted a cost-utility analysis using a Markov model from a US-payer perspective over a lifetime time horizon. The hypothetical cohort was 35-year-old patients with HBeAg-positive CHB. We evaluated 2 years of treatment with entecavir 0.5mg/day versus lamivudine 100mg/day, plus addition of adefovir 10mg/day for patients who developed virologic breakthrough due to resistance to either drug. In a scenario analysis, we considered adefovir plus lamivudine combination therapy for treatment-naive patients. Clinical and economic inputs ($US, year 2006 values) were derived from publicly available data, and probabilistic sensitivity analyses were conducted to evaluate uncertainty in the results.
  
  
  RESULTS
  The estimated 10-year cumulative incidence of cirrhosis for patients initiated on entecavir was 2.3% lower than for those on lamivudine (20.5% vs 22.8%). The discounted incremental cost per QALY gained was $US7600 in the base-case analysis, and the 95% central range from probabilistic sensitivity analysis was $US2500-$US19 100. Combination therapy for treatment-naive patients led to an increase in costs without improvement in patient outcomes compared with entecavir monotherapy.
  
  
  CONCLUSIONS
  Our analysis suggests entecavir improves health outcomes in a cost-effective manner compared with lamivudine with adefovir salvage or combination therapy, and highlights the importance of using evidence-based effectiveness estimates in economic studies of CHB therapies.
authors.affiliation: Pharmaceutical Outcomes Research and Policy Program, Department of Pharmacy, University of Washington, Seattle, Washington 98195, USA. veenstra@u.washington.edu
authors.forename: David L
authors.initials: DL
authors.lastname: Veenstra
authors.forename: Sean D
authors.initials: SD
authors.lastname: Sullivan
authors.forename: Lauren
authors.initials: L
authors.lastname: Clarke
authors.forename: Uche H
authors.initials: UH
authors.lastname: Iloeje
authors.forename: Eskinder
authors.initials: E
authors.lastname: Tafesse
authors.forename: Adrian
authors.initials: A
authors.lastname: Di Bisceglie
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gish
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000191:economics / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000191:economics* / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000191:economics* / Q000627:therapeutic use*; D015331:Cohort Studies; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D006147:Guanine / Q000031:analogs & derivatives* / Q000191:economics / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000378:metabolism*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000191:economics*; D006801:Humans; D019259:Lamivudine / Q000191:economics* / Q000627:therapeutic use*; D008390:Markov Chains; D063065:Organophosphonates / Q000191:economics* / Q000627:therapeutic use*; D011788:Quality of Life; D016879:Salvage Therapy / Q000191:economics*
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine