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Early Treatment in HCV: Is it a Cost-Utility Option from the Italian Perspective?

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Abstract

Background and 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.

Conclusion

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.

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References

  1. Global Burden Of Hepatitis CWG. Global burden of disease (GBD) for hepatitis C. J Clin Pharmacol. 2004;44:20–9.

    Article  Google Scholar 

  2. European Centre for Disease Prevention and Control. Hepatitis B and C in the EU neighbourhood: prevalence, burden of disease and screening policies. 2010.

  3. Camma C, Di Bona D, Schepis F, et al. Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: a meta-analysis of individual patient data. Hepatology. 2004;39:333–42.

    Article  CAS  PubMed  Google Scholar 

  4. Bruno S, Crosignani A, Facciotto C, et al. Sustained virologic response prevents the development of esophageal varices in compensated, Child-Pugh class A hepatitis C virus-induced cirrhosis. A 12-year prospective follow-up study. Hepatology. 2010;51:2069–76.

    Article  CAS  PubMed  Google Scholar 

  5. Singal AG, Volk ML, Jensen D, et al. A sustained viral response is associated with reduced liver-related morbidity and mortality in patients with hepatitis C virus. Clin Gastroenterol Hepatol. 2010;8:280–8, 88 e1.

  6. Camma C, Giunta M, Andreone P, et al. Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach. J Hepatol. 2001;34:593–602.

    Article  CAS  PubMed  Google Scholar 

  7. Morgan RL, Baack B, Smith BD, et al. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med. 2013;158:329–37.

    Article  PubMed  Google Scholar 

  8. Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368:1878–87.

    Article  CAS  PubMed  Google Scholar 

  9. Manns M, Marcellin P, Poordad F, et al. Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-2): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2014;384:414–26.

    Article  CAS  PubMed  Google Scholar 

  10. Zeuzem S, Berg T, Gane E, et al. Simeprevir increases rate of sustained virologic response among treatment-experienced patients with HCV genotype-1 infection: a phase IIb trial. Gastroenterology. 2014;146(430–41):e6.

    PubMed  Google Scholar 

  11. Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370:1889–98.

    Article  PubMed  Google Scholar 

  12. Afdhal N, Reddy KR, Nelson DR, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370:1483–93.

    Article  CAS  PubMed  Google Scholar 

  13. Ferenci P, Bernstein D, Lalezari J, et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014;370:1983–92.

    Article  PubMed  Google Scholar 

  14. Poordad F, Hezode C, Trinh R, et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med. 2014;370:1973–82.

    Article  PubMed  Google Scholar 

  15. Feld JJ, Kowdley KV, Coakley E, et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370:1594–603.

    Article  CAS  PubMed  Google Scholar 

  16. Zeuzem S, Jacobson IM, Baykal T, et al. Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370:1604–14.

    Article  CAS  PubMed  Google Scholar 

  17. Sulkowski MS, Gardiner DF, Rodriguez-Torres M, et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014;370:211–21.

    Article  CAS  PubMed  Google Scholar 

  18. Everson GT, Sims KD, Rodriguez-Torres M, et al. Efficacy of an interferon- and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 in treatment-naive patients with HCV genotype 1 infection. Gastroenterology. 2014;146:420–9.

    Article  CAS  PubMed  Google Scholar 

  19. Jacobson J, RM. G, Rodriguez-Torres. M, et al. SVR results of a once-daily regimen of simeprevir (TMC435) plus sofosbuvir (GS-7977) with or without ribavirin in cirrhotic and non-cirrhotic HCV genotype 1 treatment-naive and prior null responder patients: the COSMOS study. In: 48th Annual Meeting of the European Association for the Study of the Liver, Amsterdam, The Netherlands, April 24–28, 2013.

  20. Russo P. La Valutazione Framacoeconomica nel contesto regolatorio Italiano. Pharmacoeconomics—Italian Research Articles. 2008;10:59–75.

  21. Associazione Italiana Economia Sanitaria (AIES). Proposta di Linee-Guida per la valutazione economica degli interventi sanitari. Poilitiche Sanitarie. 2009;10:91–99.

  22. Siebert U, Alagoz O, Bayoumi AM, et al. State-transition modeling: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force–3. Value Health. 2012;15:812–20.

    Article  PubMed  Google Scholar 

  23. Mennini FS, Marcellusi A, Viti R, et al. Disponibilità a pagare e innovazione: il caso dei farmaci anti-HCV nel Sistema Sanitario Italiano. Glob Reg Health Technol Assess. 2015;2:69–77.

    Google Scholar 

  24. Loreta Kondili LF, Mallano Alessandra, Quaranta Maria Giovanna, Mirra Marco, Liliana Elena Weimer LF, Di Gregorio Massimiliano, Lucattini Stefano, Massella Maurizio, Roberta Terlizzi EO, Magnani Federica, Mattei Alessandra, Rosato Stefano, et al. LA PIATTAFORMA ITALIANA PER LO STUDIO della terapia DELLE EPATITI VIRALI (PITER): il primo grande studio nazionale sull’infezione cronica da virus dell’epatite C. Notiziario dell’Istituto Superiore di Sanità. 2015;28:3–10.

    Google Scholar 

  25. Mennini FS, Marcellusi A, Andreoni M, et al. Health policy model: long-term predictive results associated with the management of hepatitis C virus-induced diseases in Italy. ClinicoEcon Outcomes Res. 2014;6:303–10.

    PubMed  PubMed Central  Google Scholar 

  26. European Centre for Disease Prevention and Control. Annual Epidemiological Report 2013. Reporting on 2011 surveillance data and 2012 epidemic intelligence data. Stockholm: ECDC; 2013. p. 2013.

    Google Scholar 

  27. Agenzia Italiana del Farmaco (AIFA). Modello Algoritmo Terapia HCV. 2015.

  28. Manns MP, Fried MW, Zeuzem S, et al. Simeprevir with peginterferon/ribavirin for treatment of chronic hepatitis C virus genotype 1 infection: pooled safety analysis from Phase IIb and III studies. J Viral Hepatitis. 2015;22:366–75.

    Article  CAS  Google Scholar 

  29. D’Offizi G, Cammà C, Schlag M, et al. Optimisation of simeprevir triple therapy: a multivariate logistic regression model using baseline predictors. In: The 28th International Conference on Antiviral Research (ICAR), Rome, Italy, 11–15 May 2015.

  30. DAKLINZA approval price in Italy: Gazzetta Ufficiale della Repubblica Italiana, April 20, 2015.

  31. SOVALDI approval price in Italy: Gazzetta Ufficiale della Repubblica Italiana, November 12, 2014.

  32. EXVIERA approval price in Italy: Gazzetta Ufficiale della Repubblica Italiana, May 18, 2015.

  33. HARVONI approval price in Italy: Gazzetta Ufficiale della Repubblica Italiana, May 5, 2015.

  34. OLYSIO approval price in Italy: Gazzetta Ufficiale della Repubblica Italiana, November 17, 2015.

  35. Marcellusi A, Viti R, Capone A, et al. The economic burden of HCV-induced diseases in Italy. A probabilistic cost of illness model. Eur Rev Med Pharmacol Sci. 2015;19:1610–20.

    CAS  PubMed  Google Scholar 

  36. Petta S, Cabibbo G, Enea M, et al. Cost-effectiveness of sofosbuvir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C. Hepatology. 2014;59:1692–705.

    Article  PubMed  Google Scholar 

  37. Cortesi PA, Ciaccio A, Rota M, et al. Management of treatment-naive chronic hepatitis C genotype 1 patients: a cost-effectiveness analysis of treatment options. J Viral Hepatitis. 2015;22:175–83.

    Article  CAS  Google Scholar 

  38. Briggs A, Claxton K, Sculpher M. Decision modelling for health economic evaluation. New York; 2007.

  39. Giannini EG, Cucchetti A, Erroi V, et al. Surveillance for early diagnosis of hepatocellular carcinoma: how best to do it? World J Gastroenterol. 2013;19:8808–21.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Istituto Nazionale di Statistica (ISTAT). Tavole di mortalità della popolazione italiana. Ripartizione: Italia Anno: 2013. Available: http://demo.istat.it/unitav2012/index.html?lingua=ita. Accessed 25 May 2016.

  41. Craxi L, Camma C, Craxi A. HCV: the best cure possible or the best possible cure? J Viral Hepatitis. 2015;22:627–9.

    Article  CAS  Google Scholar 

  42. Negro F, Forton D, Craxi A, et al. Extrahepatic morbidity and mortality of chronic hepatitis C. Gastroenterology. 2015;149:1345–60.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. National Research Council (CNR), Institute for Research on Population and Social Policies (IRPPS), Rome, Italy

    Andrea Marcellusi

  2. Economic Evaluation and HTA (CEIS-EEHTA)-IGF Department, Faculty of Economics, University of Rome “Tor Vergata”, Rome, Italy

    Andrea Marcellusi, Raffaella Viti & Francesco Saverio Mennini

  3. Health Economics and Outcomes Research Manager HEMAR Manager Infectious Diseases, Janssen-Cilag SpA Italia, Milan, Italy

    Francesco Damele

  4. Sezione di Gastroenterologia, Di.Bi.M.I.S, Università di Palermo, Palermo, Italy

    Calogero Cammà

  5. Infectious and Tropical Diseases Unit, Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy

    Gloria Taliani

  6. Institute for Leadership and Management in Health-Kingston University London, London, UK

    Francesco Saverio Mennini

Authors
  1. Andrea Marcellusi
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  2. Raffaella Viti
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  3. Francesco Damele
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  4. Calogero Cammà
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  5. Gloria Taliani
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  6. Francesco Saverio Mennini
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Corresponding author

Correspondence to Andrea Marcellusi.

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Declaration of Funding

This analysis was funded by Janssen-Cilag SpA. The authors confirm that the paper is an accurate representation of the study results. FD is an employee of the sponsor and was involved in the study design, data collection and analysis, interpretation of data.

Conflict of interest

FD is employee of Janssen-Cilag SpA.

GT, CC has received consulting fees from Janssen-Cilag SpA, MSD.

AM, RV and FSM declare that there is no conflict of interest regarding the publication of this paper.

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Marcellusi, A., Viti, R., Damele, F. et al. Early Treatment in HCV: Is it a Cost-Utility Option from the Italian Perspective?. Clin Drug Investig 36, 661–672 (2016). https://doi.org/10.1007/s40261-016-0414-y

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