Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Public Health Pharmacogenomics

Free Access

Cost-Effectiveness of IL28Β Genotype-Guided Protease Inhibitor Triple Therapy versus Standard of Care Treatment in Patients with Hepatitis C Genotypes 2 or 3 Infection

Bock J.A.a · Fairley K.J.b · Smith R.E.b · Maeng D.D.c · Pitcavage J.M.c · Inverso N.A.b · Williams M.S.d

Author affiliations

aWeis Center for Research, bDepartment of Gastroenterology, cCenter for Health Research, and dGenomic Medicine Institute, Geisinger Medical Center, Danville, Pa., USA

Corresponding Author

Marc S. Williams

Genomic Medicine Institute, Geisinger Medical Center

100 N. Academy Avenue

Danville, PA 17822 (USA)

E-Mail mswilliams1@geisinger.edu

Related Articles for ""

Public Health Genomics 2014;17:306-319

Do you have an account?

Login Information





Contact Information











I have read the Karger Terms and Conditions and agree.



Abstract

Background/Aims: Triple therapy [adding protease inhibitors to standard of care (SOC)] dramatically increases treatment response in selected patients with hepatitis C virus (HCV). Interleukin 28B (IL28Β) genotyping helps predict responsiveness in these patients; however, the economic implications of IL28Β genotyping in HCV genotype 2 or 3 infected patients are unknown. Short- and long-term costs and outcomes of SOC therapy were calculated and used to determine the cost-effectiveness thresholds for using triple therapy in HCV genotype 2 or 3 infected patients. Methods: Costs and outcomes were calculated by conducting cohort simulations on decision trees modeling SOC and triple therapy. Quality-adjusted life expectancies and long-term costs were predicted through Markov modeling. Results: For triple therapy to be cost-effective, sustained virologic response (SVR) rates must improve (depending on age) by 7.91-11.11 and 9.06-12.8% for HCV genotype 2 and 3 cohorts, respectively. When triple therapy is guided by 2 IL28Β variants, a 2.63-3.72% improvement in SVR is needed for cost-effectiveness, and when guided by only one variant, a 1.4-8.91% improvement is needed. Conclusions: Markov modeling revealed that modest increases in SVR rates from IL28Β-guided triple therapy can lead to both lower costs and better health outcomes than SOC therapy in the long run.

© 2014 S. Karger AG, Basel


References

  1. Smith BD, Morgan RL, Beckett GA, Falck-Ytter Y, Holtzman D, Ward JW: Hepatitis C virus testing of persons born during 1945 to 1965: recommendations from the Centers for Disease Control and Prevention. Ann Intern Med 2012;157:817-822.
  2. McCombs JS, Yuan Y, Shin J, Saab S: Economic burden associated with patients diagnosed with hepatitis C. Clin Ther 2011;33:1268-1280.
  3. Ghany MG, Nelson DR, Strader DB, Thomas DL, Seeff LB; American Association for Study of Liver Diseases: An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology 2011;54:1433-1444.
  4. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK: Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358:958-965.
  5. Andriulli A, Mangia A, Iacobellis A, Ippolito A, Leandro G, Zeuzem S: Meta-analysis: the outcome of anti-viral therapy in HCV genotype 2 and genotype 3 infected patients with chronic hepatitis. Aliment Pharmacol Ther 2008;28:397-404.
  6. Fischer J, Böhm S, Scholz M, Müller T, Witt H, George J, Sarrazin C, Susser S, Schott E, Suppiah V, Booth DR, Stewart GJ, van Bömmel F, Brodzinski A, Fülöp B, Migaud P, Berg T: Combined effects of different interleukin-28B gene variants on the outcome of dual combination therapy in chronic hepatitis C virus type 1 infection. Hepatology 2012;55:1700-1710.
  7. Sarrazin C, Susser S, Doehring A, Lange CM, Müller T, Schlecker C, Herrmann E, Lötsch J, Berg T: Importance of IL28B gene polymorphisms in hepatitis C virus genotype 2 and 3 infected patients. J Hepatol 2011;54:415-421.
  8. Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, Marcellin P, Muir AJ, Ferenci P, Flisiak R, George J, Rizzetto M, Shouval D, Sola R, Terg RA, Yoshida EM, Adda N, Bengtsson L, Sankoh AJ, Kieffer TL, George S, Kauffman RS, Zeuzem S; ADVANCE Study Team: Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011;364:2405-2416.
  9. Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP; SPRINT-2 Investigators: Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011;364:1195-1206.
  10. Chayama K, Hayes CN, Abe H, Miki D, Ochi H, Karino Y, Toyota J, Nakamura Y, Kamatani N, Sezaki H, Kobayashi M, Akuta N, Suzuki F, Kumada H: IL28B but not ITPA polymorphism is predictive of response to pegylated interferon, ribavirin, and telaprevir triple therapy in patients with genotype 1 hepatitis C. J Infect Dis 2011;204:84-93.
  11. Lin C, Hanzelka BL, Müh U, Kovari L, Bartels DJ, Tigges AM, Miller J, Rao BG, Kwong AD: Telaprevir (VX-950) is a potent inhibitor of HCV NS3-4A proteases derived from genotype non-1 HCV infected patients. J Hepatol 2007;46(suppl 1):S8.
  12. Foster GR, Hézode C, Bronowicki JP, Carosi G, Weiland O, Verlinden L, van Heeswijk R, van Baelen B, Picchio G, Beumont M: Telaprevir alone or with peginterferon and ribavirin reduces HCV RNA in patients with chronic genotype 2 but not genotype 3 infections. Gastroenterology 2011;141:881-889.e1.
  13. Cammà C, Petta S, Enea M, Bruno R, Bronte F, Capursi V, Cicchetti A, Colombo GL, Di Marco V, Gasbarrini A, Craxi A; WEF Study Group: Cost-effectiveness of boceprevir or telaprevir for untreated patients with genotype 1 chronic hepatitis C. Hepatology 2012;56:850-860.
  14. Lindh M, Lagging M, Färkkilä M, Langeland N, Mørch K, Nilsson S, Norkrans G, Pedersen C, Buhl MR, Westin J, Hellstrand K: Interleukin 28B gene variation at rs12979860 determines early viral kinetics during treatment in patients carrying genotypes 2 or 3 of hepatitis C virus. J Infect Dis 2011;203:1748-1752.
  15. Siebert U, Sroczynski G, Rossol S, Wasem J, Ravens-Sieberer U, Kurth BM, Manns MP, McHutchison JG, Wong JB; German Hepatitis C Model (GEHMO) Group; International Hepatitis Interventional Therapy (IHIT) Group: Cost effectiveness of peginterferon alpha-2b plus ribavirin versus interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C. Gut 2003;52:425-432.
  16. Cardinal Health. Pharmaceutical Distribution; Entelligence Version 6.0.
  17. United States Department of Veterans Affairs: Hepatitis C, Antiviral TX Strategy, Genotype 2-3. 2006.
  18. Centers for Medicare and Medicaid Services, American Medical Association: Clinical Diagnostic Laboratory Fee Schedule 2012.
  19. Llovet JM, Mas X, Aponte JJ, Fuster J, Navasa M, Christensen E, Rodés J, Bruix J: Cost effectiveness of adjuvant therapy for hepatocellular carcinoma during the waiting list for liver transplantation. Gut 2002;50:123-128.
  20. Ogawa E, Furusyo N, Kajiwara E, Takahashi K, Nomura H, Maruyama T, Tanabe Y, Satoh T, Nakamuta M, Kotoh K, Azuma K, Dohmen K, Shimoda S, Hayashi J; Kyushu University Liver Disease Study (KULDS) Group: Efficacy of pegylated interferon alpha-2b and ribavirin treatment on the risk of hepatocellular carcinoma of patients with chronic hepatitis C: a prospective, multicenter study. J Hepatol 2013;58:495-501.
  21. Salomon JA, Weinstein MC, Hammitt JK, Goldie SJ: Cost-effectiveness of treatment for chronic hepatitis C infection in an evolving patient population. JAMA 2003;290:228-237.
  22. Arias E: United States Life Tables 2008. NVSS 2012;61.
  23. Neumann PJ, Greenberg D, Olchanski NV, Stone PW, Rosen AB: Growth and quality of the cost-utility literature, 1976-2001. Value Health 2005;8:3-9.
  24. Frei P, Leucht AK, Held U, Kofmehl R, Manser CN, Schmitt J, Mertens J, Rau M, Baur K, Gerlach T, Negro F, Heim M, Moradpour D, Cerny A, Dufour JF, Müllhaupt B, Geier A; Swiss Hepatitis C Cohort Study Group: Elderly age is not a negative predictive factor for virological response to therapy with pegylated interferon-alpha and ribavirin in chronic hepatitis C virus patients. Liver Int 2014;34:551-557.
  25. Sullivan SD, Jensen DM, Bernstein DE, Hassanein TI, Foster GR, Lee SS, Cheinquer H, Craxi A, Cooksley G, Klaskala W, Pettit K, Patel KK, Green J: Cost-effectiveness of combination peginterferon alpha-2a and ribavirin compared with interferon alpha-2b and ribavirin in patients with chronic hepatitis C. Am J Gastroenterol 2004;99:1490-1496.

Article / Publication Details

First-Page Preview
Abstract of Public Health Pharmacogenomics

Published online: September 18, 2014
Issue release date: December 2014

Number of Print Pages: 14
Number of Figures: 4
Number of Tables: 2

ISSN: 1662-4246 (Print)
eISSN: 1662-8063 (Online)

For additional information: https://www.karger.com/PHG


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.