Original Research5 May 2015
    Author, Article, and Disclosure Information

    Abstract

    Background:

    Chronic infection with hepatitis C virus (HCV) genotype 2 or 3 can be treated with sofosbuvir without interferon. Because sofosbuvir is costly, its benefits should be compared with the additional resources used.

    Objective:

    To estimate the cost-effectiveness of sofosbuvir-based treatments for HCV genotype 2 or 3 infection in the United States.

    Design:

    Monte Carlo simulation, including deterministic and probabilistic sensitivity analyses.

    Data Sources:

    Randomized trials, observational cohorts, and national health care spending surveys.

    Target Population:

    8 patient types defined by HCV genotype (2 vs. 3), treatment history (naive vs. experienced), and cirrhosis status (noncirrhotic vs. cirrhotic).

    Time Horizon:

    Lifetime.

    Perspective:

    Payer.

    Intervention:

    Sofosbuvir-based therapies, pegylated interferon–ribavirin, and no therapy.

    Outcome Measures:

    Discounted quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs).

    Results of Base-Case Analysis:

    The ICER of sofosbuvir-based treatment was less than $100 000 per QALY in cirrhotic patients (genotype 2 or 3 and treatment-naive or treatment-experienced) and in treatment-experienced noncirrhotic patients but was greater than $200 000 per QALY in treatment-naive noncirrhotic patients.

    Results of Sensitivity Analysis:

    The ICER of sofosbuvir-based therapy for treatment-naive noncirrhotic patients with genotype 2 or 3 infection was less than $100 000 per QALY when the cost of sofosbuvir was reduced by approximately 40% and 60%, respectively. In probabilistic sensitivity analyses, cost-effectiveness conclusions were robust to uncertainty in treatment efficacy.

    Limitation:

    The analysis did not consider possible benefits of preventing HCV transmission.

    Conclusion:

    Sofosbuvir provides good value for money for treatment-experienced patients with HCV genotype 2 or 3 infection and those with cirrhosis. At their current cost, sofosbuvir-based regimens for treatment-naive noncirrhotic patients exceed willingness-to-pay thresholds commonly cited in the United States.

    Primary Funding Source:

    National Institute on Drug Abuse and National Institute of Allergy and Infectious Diseases.

    References

    • 1. U.S. Food and Drug Administration. Approval of Sovaldi (sofosbuvir) tablets for the treatment of chronic hepatitis C. Silver Spring, MD: U.S. Food and Drug Administration; 2013. Accessed at www.fda.gov/ForPatients/Illness/HepatitisBC/ucm377920.htm on 7 February 2014. Google Scholar
    • 2. Lawitz EMangia AWyles DRodriguez-Torres MHassanein TGordon SCet alSofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med2013;368:1878-87. [PMID: 23607594] doi:10.1056/NEJMoa1214853 CrossrefMedlineGoogle Scholar
    • 3. Jacobson IMGordon SCKowdley KVYoshida EMRodriguez-Torres MSulkowski MSet alPOSITRON StudySofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med2013;368:1867-77. [PMID: 23607593] doi:10.1056/NEJMoa1214854 CrossrefMedlineGoogle Scholar
    • 4. van der Meer AJVeldt BJFeld JJWedemeyer HDufour JFLammert Fet alAssociation between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA2012;308:2584-93. [PMID: 23268517] doi:10.1001/jama.2012.144878 CrossrefMedlineGoogle Scholar
    • 5. Mehta SHGenberg BLAstemborski JKavasery RKirk GDVlahov Det alLimited uptake of hepatitis C treatment among injection drug users. J Community Health2008;33:126-33. [PMID: 18165889] doi:10.1007/s10900-007-9083-3 CrossrefMedlineGoogle Scholar
    • 6. Micromedex 2.0. Drug Topics Red Book Online. Truven Health Analytics; 2013. Accessed at www.micromedexsolutions.com on 25 June 2013. Google Scholar
    • 7. Reau NSJensen DMSticker shock and the price of new therapies for hepatitis C: is it worth it? [Editorial]. Hepatology2014;59:1246-9. [PMID: 24493069] doi:10.1002/hep.27039 CrossrefMedlineGoogle Scholar
    • 8. Armstrong D. Hepatitis C Drug Price Limiting State Medicaid Approvals. Bloomberg Business. 5 March 2014. Accessed at www.bloomberg.com/news/2014-03-05/hepatitis-c-drug-price-limiting-state-medicaid-approvals.html on 3 April 2014. Google Scholar
    • 9. Linas BPBarter DMLeff JADiLorenzo MSchackman BRHorsburgh CRet alThe cost-effectiveness of improved hepatitis C virus therapies in HIV/hepatitis C virus coinfected patients. AIDS2014;28:365-76. [PMID: 24670522] doi:10.1097/QAD.0000000000000093 CrossrefMedlineGoogle Scholar
    • 10. Linas BPBarter DMLeff JAAssoumou SASalomon JAWeinstein MCet alThe hepatitis C cascade of care: identifying priorities to improve clinical outcomes. PLoS One2014;9:e97317. [PMID: 24842841] doi:10.1371/journal.pone.0097317 CrossrefMedlineGoogle Scholar
    • 11. Gold MRSiegel JERussell LBWeinstein MCCost-Effectiveness in Health and Medicine. New York: Oxford Univ Pr; 1996. Google Scholar
    • 12. Drummond MFSculpher MTorrance GO'Brien BStoddart GMethods for the Economic Evaluation of Health Care Programmes. 3rd ed. Oxford, United Kingdom: Oxford Univ Pr; 2005. Google Scholar
    • 13. Cantor SBCost-effectiveness analysis, extended dominance, and ethics: a quantitative assessment. Med Decis Making1994;14:259-65. [PMID: 7934713] CrossrefMedlineGoogle Scholar
    • 14. Schackman BRTeixeira PAWeitzman GMushlin AIJacobson IMQuality-of-life tradeoffs for hepatitis C treatment: do patients and providers agree? Med Decis Making2008;28:233-42. [PMID: 18349430] doi:10.1177/0272989X07311753 CrossrefMedlineGoogle Scholar
    • 15. Stepanova MNader FCure SBourhis FHunt SYounossi ZMPatients' preferences and health utility assessment with SF-6D and EQ-5D in patients with chronic hepatitis C treated with sofosbuvir regimens. Aliment Pharmacol Ther2014;40:676-85. [PMID: 25040192] doi:10.1111/apt.12880 CrossrefMedlineGoogle Scholar
    • 16. Stein KDalziel KWalker AMcIntyre LJenkins BHorne Jet alScreening for hepatitis C among injecting drug users and in genitourinary medicine clinics: systematic reviews of effectiveness, modelling study and national survey of current practice. Health Technol Assess2002;6:1-122. [PMID: 12583820] CrossrefMedlineGoogle Scholar
    • 17. Siebert USroczynski GRossol SWasem JRavens-Sieberer UKurth BMet alGerman Hepatitis C Model (GEHMO) GroupCost effectiveness of peginterferon alpha-2b plus ribavirin versus interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C. Gut2003;52:425-32. [PMID: 12584228] CrossrefMedlineGoogle Scholar
    • 18. Chong CAGulamhussein AHeathcote EJLilly LSherman MNaglie Get alHealth-state utilities and quality of life in hepatitis C patients. Am J Gastroenterol2003;98:630-8. [PMID: 12650799] CrossrefMedlineGoogle Scholar
    • 19. Grieve RRoberts JWright MSweeting MDeAngelis DRosenberg Wet alCost effectiveness of interferon alpha or peginterferon alpha with ribavirin for histologically mild chronic hepatitis C. Gut2006;55:1332-8. [PMID: 15994216] CrossrefMedlineGoogle Scholar
    • 20. Sherman KEMuir AAggarwal JDonepudi MGoss TMartin Met alHealth-related quality-of-life among genotype 1 treatment-experienced chronic hepatitis C patients: post-hoc analyses from the REALIZE Study [Abstract]. Presented at The International Liver Congress 2013, Amsterdam, the Netherlands, 24–28 April 2013. J Hepatol2013;58:S372. CrossrefGoogle Scholar
    • 21. Yoshida HArakawa YSata MNishiguchi SYano MFujiyama Set alInterferon therapy prolonged life expectancy among chronic hepatitis C patients. Gastroenterology2002;123:483-91. [PMID: 12145802] CrossrefMedlineGoogle Scholar
    • 22. Barnett PGZaric GSBrandeau MLThe cost-effectiveness of buprenorphine maintenance therapy for opiate addiction in the United States. Addiction2001;96:1267-78. [PMID: 11672491] CrossrefMedlineGoogle Scholar
    • 23. Chaiwat OLang JDVavilala MSWang JMacKenzie EJJurkovich GJet alEarly packed red blood cell transfusion and acute respiratory distress syndrome after trauma. Anesthesiology2009;110:351-60. [PMID: 19164959] doi:10.1097/ALN.0b013e3181948a97 CrossrefMedlineGoogle Scholar
    • 24. American Association for the Study of Liver Diseases, Infectious Diseases Society of America. Recommendations for Testing, Managing, and Treating Hepatitis C. Alexandria, VA: American Association for the Study of Liver Diseases, Infectious Diseases Society of America; 2015. Accessed at www.hcvguidelines.org on 5 January 2015. Google Scholar
    • 25. Centers for Medicare & Medicaid Services. Clinical Laboratory Fee Schedule. Baltimore: Centers for Medicare & Medicaid Services; 2013. Accessed at www.cms.gov/ClinicalLabFeesched on 20 June 2013. Google Scholar
    • 26. Centers for Medicare & Medicaid Services. Physician Fee Schedule. Baltimore: Centers for Medicare & Medicaid Services; 2013. Accessed at www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/PhysicianFeeSched/index.html?redirect=/PhysicianFeeSched on 15 July 2013. Google Scholar
    • 27. Davis KLMitra DMedjedovic JBeam CRustgi VDirect economic burden of chronic hepatitis C virus in a United States managed care population. J Clin Gastroenterol2011;45:e17-24. [PMID: 20628308] doi:10.1097/MCG.0b013e3181e12c09 CrossrefMedlineGoogle Scholar
    • 28. Agency for Healthcare Research and Quality. Total Health Services—Mean and Median Expenses per Person With Expense and Distribution of Expenses by Source of Payment. Medical Expenditure Panel Survey Household Component Data. Rockville, MD: Agency for Healthcare Research and Quality; 2013. Accessed at http://meps.ahrq.gov/mepsweb on 15 July 2013. Google Scholar
    • 29. Lawitz EPoordad FBrainard DMHyland RHAn DDvory-Sobol Het alSofosbuvir with peginterferon-ribavirin for 12 weeks in previously treated patients with hepatitis C genotype 2 or 3 and cirrhosis. Hepatology2015;61:769-75. [PMID: 25322962] doi:10.1002/hep.27567 CrossrefMedlineGoogle Scholar
    • 30. Zeuzem SDusheiko GMSalupere RMangia AFlisiak RHyland RHet alVALENCE InvestigatorsSofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med2014;370:1993-2001. [PMID: 24795201] doi:10.1056/NEJMoa1316145 CrossrefMedlineGoogle Scholar
    • 31. Bruno SZuin MCrosignani ARossi SZadra FRoffi Let alPredicting mortality risk in patients with compensated HCV-induced cirrhosis: a long-term prospective study. Am J Gastroenterol2009;104:1147-58. [PMID: 19352340] doi:10.1038/ajg.2009.31 CrossrefMedlineGoogle Scholar
    • 32. Thein HHYi QDore GJKrahn MDEstimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: a meta-analysis and meta-regression. Hepatology2008;48:418-31. [PMID: 18563841] doi:10.1002/hep.22375 CrossrefMedlineGoogle Scholar
    • 33. Poynard TBedossa POpolon PNatural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet1997;349:825-32. [PMID: 9121257] CrossrefMedlineGoogle Scholar
    • 34. Freeman AJDore GJLaw MGThorpe MVon Overbeck JLloyd ARet alEstimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology2001;34:809-16. [PMID: 11584380] CrossrefMedlineGoogle Scholar
    • 35. Shiffman MLSuter FBacon BRNelson DHarley HSolá Ret alACCELERATE InvestigatorsPeginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N Engl J Med2007;357:124-34. [PMID: 17625124] CrossrefMedlineGoogle Scholar
    • 36. Barton GRBriggs AHFenwick EAOptimal cost-effectiveness decisions: the role of the cost-effectiveness acceptability curve (CEAC), the cost-effectiveness acceptability frontier (CEAF), and the expected value of perfection information (EVPI). Value Health2008;11:886-97. [PMID: 18489513] doi:10.1111/j.1524-4733.2008.00358.x CrossrefMedlineGoogle Scholar
    • 37. McAdam-Marx CMcGarry LJHane CABiskupiak JDeniz BBrixner DIAll-cause and incremental per patient per year cost associated with chronic hepatitis C virus and associated liver complications in the United States: a managed care perspective. J Manag Care Pharm2011;17:531-46. [PMID: 21870894] CrossrefMedlineGoogle Scholar
    • 38. Linas BPWang BSmurzynski MLosina EBosch RJSchackman BRet alThe impact of HIV/HCV co-infection on health care utilization and disability: results of the ACTG Longitudinal Linked Randomized Trials (ALLRT) Cohort. J Viral Hepat2011;18:506-12. [PMID: 20546501] doi:10.1111/j.1365-2893.2010.01325.x CrossrefMedlineGoogle Scholar
    • 39. Daltro-Oliveira RMorais-de-Jesus MPettersen KMParaná RQuarantini LCImpact of sustained virologic response on quality of life in chronic HVC carriers. Ann Hepatol2013;12:399-407. [PMID: 23619256] CrossrefMedlineGoogle Scholar
    • 40. Rodger AJJolley DThompson SCLanigan ACrofts NThe impact of diagnosis of hepatitis C virus on quality of life. Hepatology1999;30:1299-301. [PMID: 10534353] CrossrefMedlineGoogle Scholar
    • 41. Vera-Llonch MMartin MAggarwal JDonepudi MBayliss MGoss Tet alHealth-related quality of life in genotype 1 treatment-naíve chronic hepatitis C patients receiving telaprevir combination treatment in the ADVANCE study. Aliment Pharmacol Ther2013;38:124-33. [PMID: 23725204] doi:10.1111/apt.12354 CrossrefMedlineGoogle Scholar
    • 42. Singal AGVolk MLJensen DDi Bisceglie AMSchoenfeld PSA sustained viral response is associated with reduced liver-related morbidity and mortality in patients with hepatitis C virus. Clin Gastroenterol Hepatol2010;8:280-8, 288. [PMID: 19948249] doi:10.1016/j.cgh.2009.11.018 CrossrefMedlineGoogle Scholar
    • 43. Sangiovanni APrati GMFasani PRonchi GRomeo RManini Met alThe natural history of compensated cirrhosis due to hepatitis C virus: a 17-year cohort study of 214 patients. Hepatology2006;43:1303-10. [PMID: 16729298] CrossrefMedlineGoogle Scholar
    • 44. Sulkowski MSSherman KEDieterich DTBsharat MMahnke LRockstroh JKet alCombination therapy with telaprevir for chronic hepatitis C virus genotype 1 infection in patients with HIV: a randomized trial. Ann Intern Med2013;159:86-96. [PMID: 23685940] doi:10.7326/0003-4819-159-2-201307160-00654 LinkGoogle Scholar
    • 45. Pearlman BLTraub NSustained virologic response to antiviral therapy for chronic hepatitis C virus infection: a cure and so much more. Clin Infect Dis2011;52:889-900. [PMID: 21427396] doi:10.1093/cid/cir076 CrossrefMedlineGoogle Scholar
    • 46. Kim AYManagement algorithm for genotype 1 hepatitis C virus. F1000Prime Rep2013;5:24. [PMID: 23864931] doi:10.12703/P5-24 CrossrefMedlineGoogle Scholar
    • 47. Martin NKVickerman PMiners AFoster GRHutchinson SJGoldberg DJet alCost-effectiveness of hepatitis C virus antiviral treatment for injection drug user populations. Hepatology2012;55:49-57. [PMID: 21898506] doi:10.1002/hep.24656 CrossrefMedlineGoogle Scholar
    • 48. Dias PTHahn JADelwart EEdlin BMartin JLum Pet alTemporal changes in HCV genotype distribution in three different high risk populations in San Francisco, California. BMC Infect Dis2011;11:208. [PMID: 21810243] doi:10.1186/1471-2334-11-208 CrossrefMedlineGoogle Scholar
    • 49. Pianko S, Flamme SL, Shiffman ML, Kumar S, Strasser S, Dore GJ, et al. High efficacy of treatment with sofosbuvir+GS-5816+/−ribavirin for 12 weeks in treatment experienced patients with genotype 1 or 3 HCV infection [Abstract]. Presented at the American Association for the Study of Liver Diseases Liver Meeting, Boston, Massachusetts, 7–12 November 2014. Abstract no. 197. Google Scholar
    • 50. Ghany MGStrader DBThomas DLSeeff LBAmerican Association for the Study of Liver DiseasesDiagnosis, management, and treatment of hepatitis C: an update. Hepatology2009;49:1335-74. [PMID: 19330875] doi:10.1002/hep.22759 CrossrefMedlineGoogle Scholar
    • 51. Claxton KSculpher MMcCabe CBriggs AAkehurst RBuxton Met alProbabilistic sensitivity analysis for NICE technology assessment: not an optional extra. Health Econ2005;14:339-47. [PMID: 15736142] CrossrefMedlineGoogle Scholar
    • 52. Briggs AHWeinstein MCFenwick EAKarnon JSculpher MJPaltiel ADISPOR-SMDM Modeling Good Research Practices Task ForceModel parameter estimation and uncertainty: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force—6. Value Health2012;15:835-42. [PMID: 22999133] doi:10.1016/j.jval.2012.04.014 CrossrefMedlineGoogle Scholar
    • 53. Degos FChristidis CGanne-Carrie NFarmachidi JPDegott CGuettier Cet alHepatitis C virus related cirrhosis: time to occurrence of hepatocellular carcinoma and death. Gut2000;47:131-6. [PMID: 10861275] CrossrefMedlineGoogle Scholar
    • 54. Whitaker BSullivan MThe 2005 Nationwide Blood Collection and Utilization Survey Report. Washington, DC: U.S. Department of Health and Human Services; 2005. Google Scholar
    • 55. Physician's Desk Reference Web site. Accessed at www.pdr.net on 28 May 2014. Google Scholar
    • 56. Quest Diagnostics. Hepatitis C Virus (HCV) FibroSURE. Madison, NJ: Quest Diagnostics; 2013. Accessed at www.questdiagnostics.com/testcenter/BUOrderInfo.action?tc=17611&labCode=MET on 9 March 2015. Google Scholar