title: Cost-effectiveness analysis of triple therapy with protease inhibitors in treatment-naive hepatitis C patients.
abstract: BACKGROUND
  Chronic hepatitis C is the leading cause of chronic liver disease, representing a significant burden in terms of morbidity, mortality and costs. A new scenario of therapy for hepatitis C virus (HCV) genotype 1 infection is being established with the approval of two effective HCV protease inhibitors (PIs) in combination with the standard of care (SOC), peginterferon and ribavirin.
  
  
  OBJECTIVE
  Our objective was to estimate the cost effectiveness of combination therapy with new PIs (boceprevir and telaprevir) plus peginterferon and ribavirin versus SOC in treatment-naive patients with HCV genotype 1 according to data obtained from clinical trials (CTs).
  
  
  METHODS
  A Markov model simulating chronic HCV progression was used to estimate disease treatment costs and effects over patients' lifetimes, in the Spanish national public healthcare system. The target population was treatment-naive patients with chronic HCV genotype 1, demographic characteristics for whom were obtained from the published pivotal CTs SPRINT and ADVANCE. Three options were analysed for each PI based on results from the two CTs: universal triple therapy, interleukin (IL)-28B-guided therapy and dual therapy with peginterferon and ribavirin. A univariate sensitivity analysis was performed to evaluate the uncertainty of certain parameters: age at start of treatment, transition probabilities, drug costs, CT efficacy results and a higher hazard ratio for all-cause mortality for patients with chronic HCV. Probabilistic sensitivity analyses were also carried out.
  
  
  RESULTS
  Incremental cost-effectiveness ratios (ICERs) of €2012 per quality-adjusted life-year (QALY) gained were used as outcome measures. According to the base-case analysis, using dual therapy as the comparator, the alternative IL28B-guided therapy presents a more favorable ICER (€18,079/QALY for boceprevir and €25,914/QALY for telaprevir) than the universal triple therapy option (€27,594/QALY for boceprevir and €33,751/QALY for telaprevir), with an ICER clearly below the efficiency threshold for medical interventions in the Spanish setting. Sensitivity analysis showed that age at the beginning of treatment was an important factor that influenced the ICER. A potential reduction in PI costs would also clearly improve the ICER, and transition probabilities influenced the results, but to a lesser extent. Probabilistic sensitivity analyses showed that 95 % of the simulations presented an ICER below €40,000/QALY. Post hoc estimations of sustained virological responses of the IL28B-guided therapeutic option represented a limitation of the study.
  
  
  CONCLUSIONS
  The therapeutic options analysed for the base-case cohort can be considered cost-effective interventions for the Spanish healthcare framework. Sensitivity analysis estimated an acceptability threshold of the IL28B-guided strategy of patients younger than 60 years.
authors.affiliation: Departamento de Medicamentos de Uso Humano, Agencia Española de Medicamentos y Productos Sanitarios, C/Campezo 1. Edificio 8, Planta 2 Oeste E, 28022, Madrid, Spain, ablazquez@aemps.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Blázquez-Pérez
authors.forename: Ramón
authors.initials: R
authors.lastname: San Miguel
authors.forename: Javier
authors.initials: J
authors.lastname: Mar
mesh_terms: D000367:Age Factors; D000998:Antiviral Agents / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000191:economics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008390:Markov Chains; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000191:economics / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*; D019057:Quality-Adjusted Life Years; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D013030:Spain; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D009842:Oligopeptides; D011092:Polyethylene Glycols; D011392:Proline; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; C417083:peginterferon alfa-2b