Advertisement

International Journal of Clinical Pharmacy

, Volume 37, Issue 5, pp 698–708 | Cite as

Meta-analysis of the efficacy and safety of sofosbuvir for the treatment of hepatitis C virus infection

  • Hye Jin Yang
  • Ju Yeon Ryoo
  • Bong Kyu YooEmail author
Review Article

Abstract

Background Hepatitis C virus infection is a worldwide health problem and one of the leading causes of cirrhosis and hepatocellular carcinoma. Recently, sofosbuvir was introduced to the therapeutic arsenal against this virus, thereby paving the way for all-oral regimen. Aims of the review This study aimed to systematically analyze the efficacy and safety of sofosbuvir for the treatment of hepatitis C virus infection. Method PubMed and EMBASE database searches were conducted using “sofosbuvir” as the search term. Phase III clinical studies retrieved from the two databases and resources posted on the Drug@FDA and ClinicalTrials.gov websites were evaluated with regard to outcomes of the efficacy and safety analyses of the drug. Results Eight Phase III clinical studies compared the efficacy and safety of sofosbuvir. When sofosbuvir replaced peginterferon which was used in the previous standard regimen, a superior sustained virologic response, as defined by a viral RNA load less than the lower limit of quantification 12 weeks after cessation of therapy, was obtained (74.3 vs. 66.7 %, p < 0.05). The response improved even more (90.8 vs. 66.7 %, p < 0.0001) when sofosbuvir was used as an add-on therapy to the standard regimen. The overall odds ratio to achieve the response in the sofosbuvir-containing arm of the eight clinical studies was 3.66 times greater (95 % CI 3.00–4.46) than that of the standard regimen arm. During the eight clinical studies, adverse events were observed in 83.61 and 87.22 % of the patients in the sofosbuvir and non-sofosbuvir arms, respectively, with the most frequent events being mild central nervous system symptoms such as fatigue, headache, and asthenia. Conclusions Sofosbuvir was safe and effective in the treatment of hepatitis C virus genotype 1, 2, 3, or 4 infections. However, the lack of persistence of the sustained virologic response beyond the study duration and long-term safety concerns need to be addressed in future studies.

Keywords

Adverse events Hepatitis C virus Peginterferon Sofosbuvir Sustained virologic response 

Notes

Acknowledgments

The authors thank Mr. Juno Yoo and Editage for their English editing service.

Funding

This study was not supported by any external funding.

Conflicts of interest

The authors have no conflicts of interest to disclose.

References

  1. 1.
    Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect. 2011;17(2):107–15.CrossRefPubMedGoogle Scholar
  2. 2.
    Nkontchou G, Ziol M, Aout M, Lhabadie M, Baazia Y, Mahmoudi A, et al. HCV genotype 3 is associated with a higher hepatocellular carcinoma incidence in patients with ongoing viral C cirrhosis. J Viral Hepat. 2011;18(10):e516–22.CrossRefPubMedGoogle Scholar
  3. 3.
    Zeng QL, Zhang JY, Zhang Z, Wang LF, Wang FS. Sofosbuvir and ABT-450: terminator of hepatitis C virus? World J Gastroenterol. 2013;19(21):3199–206.PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Alavian SM. Sofosbuvir has come out of the magic box. Hepat Mon. 2013;13(12):e16916.PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Dugum M, O’Shea R. Hepatitis C virus: here comes all-oral treatment. Cleve Clin J Med. 2014;81(3):159–72.CrossRefPubMedGoogle Scholar
  6. 6.
    Koff RS. The efficacy and safety of sofosbuvir, a novel, oral nucleotide NS5B polymerase inhibitor, in the treatment of chronic hepatitis C virus infection. Aliment Pharmacol Ther. 2014;39(5):478–87.CrossRefPubMedGoogle Scholar
  7. 7.
    Gentile I, Borgia F, Buonomo AR, Castaldo G, Borgia G. A novel promising therapeutic option against hepatitis C virus: an oral nucleotide NS5B polymerase inhibitor sofosbuvir. Curr Med Chem. 2013;20(30):3733–42.CrossRefPubMedGoogle Scholar
  8. 8.
    Bhatia HK, Singh H, Grewal N, Natt NK. Sofosbuvir: a novel treatment option for chronic hepatitis C infection. J Pharmacol Pharmacother. 2014;5(4):278–84.PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Pockros PJ. Nucleoside/nucleotide analogue polymerase inhibitors in development. Clin Liver Dis. 2013;17(1):105–10.CrossRefPubMedGoogle Scholar
  10. 10.
    Marino Z, van Bommel F, Forns X, Berg T. New concepts of sofosbuvir-based treatment regimens in patients with hepatitis C. Gut. 2014;63(2):207–15.PubMedGoogle Scholar
  11. 11.
    Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, et al. Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010;285(45):34337–47.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Asselah T, Marcellin P. Second-wave IFN-based triple therapy for HCV genotype 1 infection: simeprevir, faldaprevir and sofosbuvir. Liver Int. 2014;34(Suppl 1):60–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Herbst DA Jr, Reddy KR. Sofosbuvir, a nucleotide polymerase inhibitor, for the treatment of chronic hepatitis C virus infection. Expert Opin Investig Drugs. 2013;22(4):527–36.CrossRefPubMedGoogle Scholar
  14. 14.
    Clinicaltrials.gov (numbers: NCT01641640, NCT01497366, NCT01542788, NCT01604850, NCT01682720, NCT01701401, NCT01768286, NCT01851330). https://clinicaltrials.gov/. Accessed 16 Mar 2015.
  15. 15.
    Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368(20):1878–87.CrossRefPubMedGoogle Scholar
  16. 16.
    Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013;368(20):1867–77.CrossRefPubMedGoogle Scholar
  17. 17.
    Zeuzem S, Dusheiko GM, Salupere R, Mangia A, Flisiak R, Hyland RH, et al. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med. 2014;370(21):1993–2001.CrossRefPubMedGoogle Scholar
  18. 18.
    Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889–98.CrossRefPubMedGoogle Scholar
  19. 19.
    Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16):1483–93.CrossRefPubMedGoogle Scholar
  20. 20.
    Kowdley KV, Gordon SC, Reddy KR, Rossaro L, Bernstein DE, Lawitz E, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370(20):1879–88.CrossRefPubMedGoogle Scholar
  21. 21.
    Chen J, Florian J, Carter W, Fleischer RD, Hammerstrom TS, Jadhav PR, et al. Earlier sustained virologic response end points for regulatory approval and dose selection of hepatitis C therapies. Gastroenterology. 2013;144(7):1450–5.CrossRefPubMedGoogle Scholar
  22. 22.
    Yoshida EM, Sulkowski MS, Gane EJ, Herring RW Jr, Ratziu V, Ding X, et al. Concordance of sustained virologic response 4, 12, and 24 weeks post-treatment with sofosbuvir-containing regimens for hepatitis C virus. Hepatology. 2015;61(1):41–5.CrossRefPubMedGoogle Scholar
  23. 23.
  24. 24.
    Averhoff FM, Glass N, Holtzman D. Global burden of hepatitis C: considerations for healthcare providers in the United States. Clin Infect Dis. 2012;55(suppl 1):S10–5.CrossRefPubMedGoogle Scholar
  25. 25.
    Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 2006;45(4):529–38.CrossRefPubMedGoogle Scholar
  26. 26.
    Ward RP, Kugelmas M. Using pegylated interferon and ribavirin to treat patients with chronic hepatitis C. Am Fam Physician. 2005;72(4):655–62.PubMedGoogle Scholar
  27. 27.
    American Association for the Study of Liver Diseases. Recommendations for testing, managing, and treating hepatitis C. http://hcvguidelines.org/fullreport. Accessed 4 Dec 2014.
  28. 28.
    European Association for the Study of the Liver (EASL). Recommendations on treatment of hepatitis C 2014. http://files.easl.eu/easl-recommendations-on-treatment-of-hepatitis-C/index.html. Accessed 4 Dec 2014.
  29. 29.
    Timm J, Roggendorf M. Sequence diversity of hepatitis C virus: implications for immune control and therapy. World J Gastroenterol. 2007;13(36):4808–17.PubMedGoogle Scholar
  30. 30.
    Zhu Y, Chen S. Antiviral treatment of hepatitis C virus infection and factors affecting efficacy. World J Gastroenterol. 2013;19(47):8960–73.CrossRefGoogle Scholar
  31. 31.
    Soriano V, Vispo E, de Mendoza C, Labarga P, Fernandez-Montero JV, Poveda E, et al. Hepatitis C therapy with HCV NS5B polymerase inhibitors. Expert Opin Pharmacother. 2013;14(9):1161–70.CrossRefPubMedGoogle Scholar
  32. 32.
    Goozner M. Why Sovaldi shouldn’t cost $84,000. Mod Healthc. 2014;44(18):26.Google Scholar
  33. 33.
    Hagan LM, Sulkowski MS, Schinazi RF. Cost analysis of sofosbuvir/ribavirin versus sofosbuvir/simeprevir for genotype 1 hepatitis C virus in interferon-ineligible/intolerant individuals. Hepatology. 2014;60(1):37–45.PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Support Path Program. http://www.mysupportpath.com/. Accessed 4 Dec 2014.

Copyright information

© Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2015

Authors and Affiliations

  1. 1.College of PharmacyGachon UniversityIncheonKorea

Personalised recommendations