Successful treatment of hepatitis C virus (HCV) infection is reflected by a sustained virologic response (SVR), which is the absence of detectable levels of viral genetic material in the blood 24 weeks after completion of therapy. The current standard treatment for chronic HCV infection has been a combination of peginterferon-α and ribavirin (PR) for 24 to 48 weeks, which, acting on non-specific pathways, has suboptimal SVR and significant toxicity in treated patients. Recently, new drugs that act on specific targets in the viral life cycle have been developed to directly inhibit viral production. These drugs, referred as direct-acting antiviral medications (DAA), and included protease inhibitors such as boceprevir and telaprevir, can be used alone, together with another DAA, or combined with PR. Boceprevir and telaprevir, approved by Health Canada in 2011, have demonstrated high cure rates when used together with PR, but adverse event rates and low spectrum activity (genotype 1) have been barriers to their use. In order to improve the pharmacokinetics and tolerability of DAA, a second generation of protease inhibitors such as simeprevir and sofosbuvir have been recently developed and approved for use in Canada in 2013 and 2014, respectively. Simeprevir and sofosbuvir can be used as first-line therapy for the treatment of HCV infection, or because of the high costs associated with the new DAA, in patients who had not responded to standard treatment or first generation DAA. A recent Therapeutic Review report by CADTH recommended simeprevir for treatment-naïve or -experienced patients with genotype 1 HCV, but could not make a recommendation for sofosbuvir due to a lack of evidence.

This Rapid Response report aims to review the clinical effectiveness and safety of simeprevir and/or sofosbuvir combined with PR in patients with chronic hepatitis C genotype 1, 2, 3 or 4 who have had an inadequate response to prior DAA plus PR therapy or prior treatment with PR alone.

Contents

• CONTEXT AND POLICY ISSUES
• RESEARCH QUESTIONS
• KEY FINDINGS
• METHODS
  • Literature Search Strategy
  • Selection Criteria and Methods
  • Exclusion Criteria
  • Critical Appraisal of Individual Studies
• SUMMARY OF EVIDENCE
  • Quantity of Research Available
  • Summary of Study Characteristics
  • Summary of Critical Appraisal
  • Summary of Findings
  • Limitations
• CONCLUSIONS AND IMPLICATIONS FOR DECISION OR POLICY MAKING
• REFERENCES
• Appendix 1 Selection of Included Studies
• Appendix 2 Characteristics of Included Studies
• Appendix 3 Summary of Critical Appraisal of Included Studies
• Appendix 4 Main Study Findings and Authors’ Conclusions

Disclaimer: The Rapid Response Service is an information service for those involved in planning and providing health care in Canada. Rapid responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list of sources of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time allowed. Rapid responses should be considered along with other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report.