AJPB

Recent Trends in the Treatment of Chronic Hepatitis C | Page 3

Published Online: April 16, 2014
Sara C. Erickson, PharmD; Wenyi Qiu, MS; Crystal R. Maas-Patel, PharmD; Sharon M. Wang, PharmD, MS; and Bimal V. Patel, PharmD, MS
Our pharmacy claims–based analysis found that 41.1% (n = 180) of patients initiating sofosbuvir or simeprevir were taking concomitant pegylated interferon and ribavirin. A greater proportion of patients (57.1%, n = 250) initiated an interferon-free sofosbuvir regimen. Most health plans covered by our PBM elected to use prior authorization guidelines to determine appropriate use for medication coverage that is consistent with approved indications and evidence-based standard of care. As the proportion of genotype 1 among the chronic HCV population in the United States is at least 70%, it is expected that a similar proportion of sofosbuvir initiators would be on the FDA-approved regimen for genotype 1 (sofosbuvir, pegylated interferon and ribavirin). It may be that a greater proportion of genotype 2 or 3 patients have initiated therapy in this early time period or that a large proportion of genotype 1 patients initiating therapy have been deemed interferon-ineligible. The cost implications of the latter scenario are significant, as treating genotype 1 patients with an interferon-free regimen costs between $58,426 and $80,491 more per patient, and with decreased efficacy. An SVR of 72% was realized in a total of 211 treatment-naïve genotype 1 patients using sofosbuvir and ribavirin in various clinical trials.32 The AASLD/IDSA guidelines recommend that the all-oral combination of sofosbuvir with ribavirin for 24 weeks should be considered only for genotype-1 patients who require immediate treatment, because regimens with improved safety and efficacy will likely be available by 2015.32

The higher costs of more efficacious treatment may be justified as the costs of treatment failure are significant. One analysis found a 10-fold difference in the costs between managing patients who achieved SVR versus those who did not achieve SVR over a 5-year period, with a retreatment rate of 19% among SVR nonachievers.35

The outstanding question is whether these new standard-of-care therapies are cost-effective. A Markov model analysis, published months before sofosbuvir was approved, determined that $112,653 was the maximum drug cost for an all-oral regimen achieving 90% SVR to remain cost-effective using a $100,000 per quality adjusted life-year willingness-to-pay threshold.36 For most patients, the current all-oral sofosbuvir-based regimens do not meet the 90% SVR standard of efficacy and are much more expensive.

The standard of care for the treatment of chronic HCV infection continues to evolve. Several novel drugs are being studied in which preliminary data demonstrate close to 100% SVR (Figure 1).37-39 The future standard of care will be oral regimens that are more effective and presumably more tolerable. Present interferon-free regimens have less evidence of efficacy and a substantial cost (between $180,881 and $202,497 per treatment) for the majority of patients who will receive these treatments. It is yet unknown if the current trend of increasing costs for chronic HCV treatment will continue, or at what point it will no longer be sustainable.

Author Affiliations: Health Outcomes Research (SCE, WQ, CRM-P, SMW, BVP).

Source of Funding: None reported.

Author Disclosures: The authors (SCE, WQ, CRM-P, SMW, BVP) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of MedImpact Healthcare Systems, Inc.

Authorship Information: Concept and design (SCE, SMW, BVP); acquisition of data (WQ); analysis and interpretation of data (SCE, WQ, CRM-P, SMW); drafting of the manuscript (SCE); critical revision of the manuscript for important intellectual content (CRM- P, SMW); statistical analysis (WQ); administrative, technical, or logistic support (CRM-P, BVP); supervision (BVP).

Address correspondence to: Sara C. Erickson, PharmD, Health Outcomes Researcher, 10181 Scripps Gateway Ct, San Diego, CA 92131. E-mail: sara.erickson@medimpact.com.
1. Denniston MM, Jiles RB, Drobeniuc J, et al. Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med. 2014;160(5):293-300.

2. Ly KN, Xing J, Klevens RM, et al. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Ann Intern Med. 2012; 156(11):271-278.

3. Denniston MM, Klevens RM, McQuillan GM, Jiles RB. Awareness of infection, knowledge of hepatitis C, and medical follow-up among individuals testing positive for hepatitis C: National Helath and Nutrition Examination Survey 2001-2008. Hepatology. 2012;55(6):1652-1661.

4. Moorman AC, Gordon SC, Rupp LB, et al. Baseline characteristics and mortality among people in care for chronic viral hepatitis: the Chronic Hepatitis Cohort Study. Clin Infect Dis. 2013;56(1):40-50.

5. Volk ML, Tocco R, Saini S, et al. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.

6. Khokhar OS, Lewis JH. Reasons why patients infected with chronic hepatitis C virus choose to defer treatment: do they alter their decision with time? Dig Dis Sci. 2007;52(5):1168-1176.

7. McGowan CE, Monis A, Bacon BR, et al. A global view of hepatitis C: physician knowledge, opinions, and perceived barriers to care. Hepatology. 2013;57(4): 1325-1332.

8. Bini EJ, Brau N, Currie S, et al. Prospective multicenter study of eligibility for antiviral therapy among 4,084 U.S. veterans with chronic hepatitis c virus infection. Am J Gastroenterol. 2005;100(8):1772-1779.

9. Hepatitis C Fact sheet N°164. World Health Organization website. http://www .who.int/mediacentre/factsheets/fs164/en/. Updated July 2013. Accessed March 7, 2014.

10. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol. 2014;60(2):392-420.

11. Davis GL, Alter MJ, El-Serag H, et al. Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138(2):513.

12. Smith BD, Morgan RL, Beckett GA, et al. Recommendations for the identifi cation of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep. 2012;61(RR-4):1-32.

13. Maylin S, Martinot M, Moucari R, et al. Eradication of hepatitis C virus in patients successfully treated for chronic hepatitis C. Gastroenterology. 2008;135(3): 821-829.

14. Camma C, DiBona D, Schepis F, et al. Effect of peginterferon alfa-2a on liver histology in chronic hepatits C: a meta-analysis of individual patient data. Hepatology. 2004;39(2):333-342.

15. George SL, Bacon BR, Brunt EM, et al. Clinical, viralogic, histologic, and biochemical outcomes after successful HCV therapy: a 5-year follow-up of 150 patients. Hepatology. 2009;49(3):729-738.

16. Morgan TR, Ghany MG, Kim HY, et al. Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology. 2010;52(3): 833-844.

17. Poynard T, McHutchison J, Manns M, et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fi brosis in patients with chronic hepatitis C. Gastroenterology. 2002;122(5):1303-3013.

18. Van der Meer AJ, Veldt BJ, Feld JJ, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fi brosis. JAMA. 2012;308(24):2584-2593.

19. Velt BJ, Heathcote EJ, Wedemeyer H, et al. Sustatined virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fi brosis. Ann Intern Med. 2007;147(10):677-684.

20. Martinot-Peignoux M, Stern C, Maylin S, et al. Twelve weeks posttreatment follow-up is as relevant as 24 weeks to determine the sustained virologic response in patients with hepatitis C virus receiving pegylated interferon and ribavirin. Hepatology. 2010;51(4):1122-1126.

21. Chen J, Florian J, Carter W, et al. Earlier sustained virologic response end points for regulatory approval and dose selection of hepatitis C therapies. Gastroenterology. 2013;144(7):1450-1455.

22. Lo Re V 3rd, Teal V, Localio AR, et al. Relationship between adherence to hepatitis C virus therapy and virologic outcomes: a cohort study. Ann Intern Med. 2011;155(6):353-360.

23. Mitra D, Davis KL, Beam C, et al. Treatment patterns and adherence among patients with chronic hepatitis C virus in a US managed care population. Value Health. 2010;13(4):479-486.

24. Redulla R, Dudley-Brown S. Adherence and completion in hepatitis C management: a systematic review. Gastroenterol Nurs. 2013;36(1):53-58.

25. Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364(25): 2405-2416.

26. Poordad F, McCone J Jr, Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364(13):1195-1206.

27. Bacon BR, Gordon SC, Lawitz E, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011;364(13):1207-1217.

28. Zeuzem S, Andreone P, Pol S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011;364(25):2417-2428.

29. Massoumy B, Port K, Calle Serrano B, et al. The clinical signifi cance of drug– drug interactions in the era of direct acting anti-viral agents against chronic hepatitis C. Aliment Pharm Ther. 2013;38(11-12):1365-1372.

30. Olysio [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals; November 2013.

31. Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368(20):1878-1887.

32. Guidance from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Disease Society of America (IDSA) Recommendations for Testing, Managing, and Treating Hepatitis C. http://www.hcvguidelines.org/ full-report-view. Accessed January 30, 2014.

33. Cohen J. Advocates protest the cost of a hepatitis C cure. Science. 2013; 342(6164):1302-1303.

34. Somashekhar S. Costly hepatitis drug Sovaldi rattles industry. Washington Post. March 1, 2014. http://www.washingtonpost.com/national/health-science/ costly-hepatitis-drug-sovaldi-rattles-industry/2014/03/01/86cab0b4-a091-1 1e3-9ba6-800d1192d08b_story.html. Accessed March 9, 2014.

35. Backx M, Lewszuk A, White JR, et al. The cost of treatment failure: resource use and costs incurred by hepatitis C virus genotype 1-infected patients who do or do not achieve sustained virological response to therapy. J Viral Hepat. 2014;21(3):208-215.

36. Hagan LM, Yang Z, Ehteshami M, et al. All-oral, interferon-free treatment for chronic hepatitis C: cost-effectiveness analyses. J Viral Hepat. 2013;20(12): 847-857.

37. Poordad F, Lawitz E, Kowdley KV, et al. Exploratory study of oral combination antiviral therapy for hepatitis C. N Engl J Med. 2013;368(1):45-53.

38. 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(3):211-221.

39. Zeuzem S, Soriano V, Asselah T, et al. Faldaprevir and deleobuvir for HCV genotype 1 infection. N Engl J Med. 2013;369(7):630-639.
Issue: March/April 2014
More on AJMC.COM