title: Early Treatment in HCV: Is it a Cost-Utility Option from the Italian Perspective?
abstract: OBJECTIVE
  In Italy, the Italian Pharmaceutical Agency (AIFA) criteria used F3-F4 fibrosis stages as the threshold to prioritise the treatment with interferon (IFN)-free regimens, while in genotype 1 chronic hepatitis C (G1 CHC) patients with fibrosis of liver stage 2, an approach with pegylated interferon (PEG-IFN)-based triple therapy with simeprevir was suggested. The key clinical question is whether, in an era of financial constraints, the application of a universal IFN-free strategy in naïve G1 CHC patients is feasible within a short time horizon. The aim of this study is to perform an economic analysis to estimate the cost-utility of the early innovative therapy in Italy for managing hepatitis C virus (HCV)-infected patients.
  
  
  METHODS
  The incremental cost-utility analysis was carried out to quantify the benefits of the early treatment approach in HCV subjects. A Markov simulation model including direct and indirect costs and health outcomes was developed from an Italian National Healthcare Service and societal perspective. A total of 5000 Monte Carlo simulations were performed on two distinct scenarios: standard of care (SoC) which includes 14,000 genotype 1 patients in Italy treated with innovative interferon-free regimens in the fibrosis of liver stages 3 and 4 (F3-F4) versus early-treatment scenario (ETS) where 2000 patients were additionally treated with simeprevir plus PEG-IFN and ribavirin in the fibrosis stage 2 (F2) (based on Italian Medicines Agency AIFA reimbursement criteria). A systematic literature review was carried out to identify epidemiological and economic data, which were subsequently used to inform the model. Furthermore, a one-way probabilistic sensitivity was performed to measure the relationship between the main parameters of the model and the cost-utility results.
  
  
  RESULTS
  The model shows that, in terms of incremental cost-effectiveness ratio (ICER) per quality adjusted life year (QALY) gained, ETS appeared to be the most cost-utility option compared with both perspective societal (ICER = EUR11,396) and NHS (ICER = EUR14,733) over a time period of 10 years. The cost-utility of ETS is more sustainable as it extends the time period analysis [ICER = EUR 6778 per QALY to 20 years and EUR4474 per QALY to 30 years]. From the societal perspective, the ETS represents the dominant option at a time horizon of 30 years. If we consider the sub-group population of treated patients [16,000 patients of which 2000 not treated in the SoC, the ETS scenario was dominant after only 5 years and the cost-utility at 2 years of simulation. The one-way sensitivity analysis on the main variables confirmed the robustness of the model for the early-treatment approach.
  
  
  CONCLUSIONS
  Our model represents a tool for policy makers and health-care professionals, and provided information on the cost-utility of the early-treatment approach in HCV-infected patients in Italy. Starting innovative treatment regimens earlier keeps HCV-infected patients in better health and reduces the incidence of HCV-related events; generating a gain both in terms of health of the patients and correct resource allocation.
authors.affiliation: National Research Council (CNR), Institute for Research on Population and Social Policies (IRPPS), Rome, Italy. andrea.marcellusi@uniroma2.it.|Economic Evaluation and HTA (CEIS-EEHTA)-IGF Department, Faculty of Economics, University of Rome "Tor Vergata", Rome, Italy. andrea.marcellusi@uniroma2.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Marcellusi
authors.affiliation: Economic Evaluation and HTA (CEIS-EEHTA)-IGF Department, Faculty of Economics, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Viti
authors.affiliation: Health Economics and Outcomes Research Manager HEMAR Manager Infectious Diseases, Janssen-Cilag SpA Italia, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Damele
authors.affiliation: Sezione di Gastroenterologia, Di.Bi.M.I.S, Università di Palermo, Palermo, Italy.
authors.forename: Calogero
authors.initials: C
authors.lastname: Cammà
authors.affiliation: Infectious and Tropical Diseases Unit, Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Taliani
authors.affiliation: Economic Evaluation and HTA (CEIS-EEHTA)-IGF Department, Faculty of Economics, University of Rome "Tor Vergata", Rome, Italy.|Institute for Leadership and Management in Health-Kingston University London, London, UK.
authors.forename: Francesco Saverio
authors.initials: FS
authors.lastname: Mennini
mesh_terms: D000998:Antiviral Agents / Q000191:economics* / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000191:economics*; D006801:Humans; D007372:Interferons / Q000191:economics / Q000627:therapeutic use; D007558:Italy / Q000453:epidemiology; D008103:Liver Cirrhosis / Q000191:economics / Q000517:prevention & control / Q000821:virology; D008390:Markov Chains; D009010:Monte Carlo Method; D019057:Quality-Adjusted Life Years; D012254:Ribavirin / Q000191:economics / Q000627:therapeutic use; D000069616:Simeprevir / Q000191:economics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D007372:Interferons; D000069616:Simeprevir