Digestive Diseases and Sciences

, Volume 59, Issue 12, pp 3043–3052 | Cite as

Effectiveness of Telaprevir and Boceprevir Triple Therapy for Patients with Hepatitis C Virus Infection in a Large Integrated Care Setting

  • Jennifer C. Price
  • Rosemary C. Murphy
  • Valentina A. Shvachko
  • Mary Pat Pauly
  • M. Michele Manos
Original Article

Abstract

Background

In 2011, the FDA approved telaprevir (TVR) and boceprevir (BOC) for use with pegylated interferon and ribavirin to treat hepatitis C virus (HCV) genotype 1. We aimed to evaluate the real-world application, tolerability, and effectiveness of TVR- and BOC-based HCV treatment in a large integrated care setting.

Methods

We utilized Northern California Kaiser Permanente Medical Care Program (KPNC) electronic databases and medical records to study the experience of all KPNC patients who initiated TVR or BOC from June 2011 to March 2012.

Results

Compared with the pool of 5,194 treatment-eligible patients, the 352 treatment initiators were more likely to be cirrhotic (24 vs. 10 %, p < 0.001) and treatment-experienced (44 vs. 22 %, p < 0.001). Among the treatment initiators, 211 received TVR and 141 BOC. Overall, 31 % discontinued treatment prematurely; 16 % of patients stopped treatment early because of side effects. One patient with cirrhosis died of sepsis during treatment. Premature discontinuation was highest among TVR-treated cirrhotic patients (58 %). Sustained virologic response (SVR) was achieved in 55 % overall and was similar comparing the TVR (56 %)- and BOC (53 %)-treated groups. The only independent predictors of treatment failure were cirrhosis at baseline [odds ratio (OR) for SVR 0.44, p = 0.004] and prior partial or null response (OR for SVR 0.57, p = 0.02).

Conclusions

In the initial application of TVR and BOC, patients with cirrhosis and prior treatment failure were prioritized for treatment. In this real-world experience, most patients successfully completed a full treatment course. However, side effect-related premature discontinuations were common, and SVR rates were lower than reported in clinical trials.

Keywords

HCV DAA Antiviral therapy Telaprevir Boceprevir 

Abbreviations

TVR

Telaprevir

BOC

Boceprevir

HCV

Hepatitis C virus

KPNC

Northern California Kaiser Permanente Medical Care Program

SVR

Sustained virologic response

OR

Odds ratio

PEG

Pegylated interferon

RBV

Ribavirin

HIV

Human immunodeficiency virus

HBV

Hepatitis B virus

VHR

Viral Hepatitis Registry

PIMS

Pharmacy information management system

LLOD

Lower limit of detection

LLOQ

Lower limit of quantification

RGT

Response-guided therapy

DRESS

Drug reaction with eosinophilia and systemic symptoms

Hgb

Hemoglobin

BMI

Body mass index

IQR

Interquartile range

VA

Veterans Affairs

References

  1. 1.
  2. 2.
    Kim WR, Stock PG, Smith JM, et al. OPTN/SRTR 2011 annual data report: liver. Am J Transpl. 2013;13:73–102.CrossRefGoogle Scholar
  3. 3.
    Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364:2405–2416.PubMedCrossRefGoogle Scholar
  4. 4.
    Zeuzem S, Andreone P, Pol S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011;364:2417–2428.PubMedCrossRefGoogle Scholar
  5. 5.
    Poordad F, McCone J Jr, Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195–1206.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Bacon BR, Gordon SC, Lawitz E, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1207–1217.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Jacobson IM, Pawlotsky JM, Afdhal NH, et al. A practical guide for the use of boceprevir and telaprevir for the treatment of hepatitis. C J Viral Hepat. 2012;19:1–26.CrossRefGoogle Scholar
  8. 8.
    Maasoumy B, Port K, Markova AA, et al. Eligibility and safety of triple therapy for hepatitis C: lessons learned from the first experience in a real world setting. PLoS One. 2013;8:e55285.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Ridruejo E, Adrover R, Cocozzella D, Reggiardo MV, Fernandez N. Effectiveness of hepatitis C treatment with pegylated interferon and ribavirin in urban minority patients Hepatology. 2010;51:2231; author reply 2231–2232.Google Scholar
  10. 10.
    Backus LI, Boothroyd DB, Phillips BR, Mole LA. Predictors of response of US veterans to treatment for the hepatitis C virus. Hepatology. 2007;46:37–47.PubMedCrossRefGoogle Scholar
  11. 11.
    Manos MM, Darbinian J, Rubin J, et al. The effect of hepatitis C treatment response on medical costs: a longitudinal analysis in an integrated care setting. J Manag Care Pharm. 2013;19:438–447.PubMedGoogle Scholar
  12. 12.
    Gordon N. Similarity of the adult Kaiser Permanente membership in northern California to the insured and general population in northern California: statistics from the 2007 California Health Interview Survey. Internal Report: Kaiser Permanente Division of Research. 2012.Google Scholar
  13. 13.
    Krieger N. Overcoming the absence of socioeconomic data in medical records: validation and application of a census-based methodology. Am J Public Health. 1992;82:703–710.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    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:e1452.Google Scholar
  15. 15.
    Manos MM, Shvachko VA, Murphy RC, Arduino JM, Shire NJ. Distribution of hepatitis C virus genotypes in a diverse US integrated health care population. J Med Virol. 2012;84:1744–1750.PubMedCrossRefGoogle Scholar
  16. 16.
    Kwo PY. Phase III results in Genotype 1 naive patients: predictors of response with boceprevir and telaprevir combined with pegylated interferon and ribavirin. Liver Int. 2012;32:39–43.PubMedCrossRefGoogle Scholar
  17. 17.
    Poordad F, Bronowicki JP, Gordon SC, et al. Factors that predict response of patients with hepatitis C virus infection to boceprevir. Gastroenterology. 2012;143:e601–e605.CrossRefGoogle Scholar
  18. 18.
    Hezode C, Fontaine H, Dorival C et al. Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC)—NCT01514890. J Hepatol. 2013;59:434–441.Google Scholar
  19. 19.
    Saxena V, Manos MM, Yee H et al. Telaprevir or boceprevir triple therapy in patients with chronic hepatitis C and varying severity of cirrhosis Aliment Pharmacol Ther (in press).Google Scholar
  20. 20.
    INCIVEK [package insert]. Cambridge, MA: Vertex Pharmaceuticals Incorporated; 2011.Google Scholar
  21. 21.
    VICTRELIS [package insert]. Whitehouse Station, NJ: Schering Corporation, a subsidiary of Merck & Co, INC; 2011.Google Scholar
  22. 22.
    Sherman KE, Flamm SL, Afdhal NH, et al. Response-guided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med. 2011;365:1014–1024.PubMedCrossRefGoogle Scholar
  23. 23.
    Ioannou GN, Beste LA, Green PK. Similar effectiveness of boceprevir and telaprevir treatment regimens for hepatitis C virus infection, based on a nationwide study of veterans Clin Gastroenterol Hepatol. 2014;12:1371–1380.Google Scholar
  24. 24.
    Backus LI, Belperio PS, Shahoumian TA, Cheung R, Mole LA. Comparative effectiveness of the hepatitis C virus protease inhibitors boceprevir and telaprevir in a large U.S. cohort. Aliment Pharmacol Ther. 2014;39:93–103.PubMedCrossRefGoogle Scholar
  25. 25.
    Wehmeyer MH, Eissing F, Jordan S, et al. Safety and efficacy of protease inhibitor based combination therapy in a single-center “real-life” cohort of 110 patients with chronic hepatitis C genotype 1 infection. BMC Gastroenterol. 2014;14:87.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Maasoumy B, Port K, Deterding K, et al. Limited effectiveness and safety profile of protease inhibitor-based triple therapy against chronic hepatitis C in a real-world cohort with a high proportion of advanced liver disease. Eur J Gastroenterol Hepatol. 2014;26:836–845.PubMedCrossRefGoogle Scholar
  27. 27.
    Belperio PS, Backus LI, Ross D, Neuhauser MM, Mole LA. A population approach to disease management: hepatitis C direct-acting antiviral use in a large health care system. J Manag Care Pharm. 2014;20:533–540.PubMedGoogle Scholar
  28. 28.
    Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368:1878–1887.PubMedCrossRefGoogle Scholar
  29. 29.
    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:e436.CrossRefGoogle Scholar
  30. 30.
    Manns M, Marcellin P, Poordad F, et al. Simeprevir (TMC435) with pegylated interferon/ribavirin for the treatment of chronic HCV genotype-1 infection in treatment-naive patients: results from QUEST-2, a phase 3 trial. J Hepatol. 2013, abstract 1413.Google Scholar
  31. 31.
    Shiffman ML, Benhamou Y. HCV F1/F2 patients: treat now or continue to wait. Liver Int. 2014;34:79–84.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Jennifer C. Price
    • 1
  • Rosemary C. Murphy
    • 2
  • Valentina A. Shvachko
    • 2
  • Mary Pat Pauly
    • 2
  • M. Michele Manos
    • 2
  1. 1.Division of Gastroenterology and Hepatology, Department of MedicineUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Viral Hepatitis Registry, Division of ResearchKaiser Permanente Northern CaliforniaOaklandUSA

Personalised recommendations