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Interferon-free Regimens for Genotype 1 Chronic Hepatitis C: A Review of the Clinical Evidence and Cost-Effectiveness

Published on: June 25, 2014
Project Number: RC0563-000
Product Line: Rapid Response
Research Type: Drug
Report Type: Summary with Critical Appraisal
Result type: Report

Report in Brief

Context
Approximately 250,000 Canadians are known to be infected with the hepatitis C virus (HCV); however, there are likely others who are unaware they are infected. Over a period of 20 to 30 years, 15% to 25% of those with chronic hepatitis C infection will develop progressive liver disease or liver cancer, or will require a liver transplant. There are six genotypes of HCV, and genotype 1 is the most common in Canada.

Technology
For many years, standard therapy for genotype 1 chronic HCV infection had been pegylated interferon plus ribavirin. Since 2011, four direct-acting antiviral (DAA) drugs have been approved for the treatment of HCV in combination with pegylated interferon plus ribavirin. This “triple therapy” increases the likelihood of a cure, but patients still experience adverse effects of interferon, which may include fatigue, flu-like symptoms, psychiatric symptoms, seizures, weight loss, peripheral neuropathy, and bone marrow suppression. DAA regimens that do not include interferon are under development.

Issue
At the time of writing, no interferon-free regimen has been approved by Health Canada. Early evidence suggests that these regimens have better side effect profiles and higher cure rates, but there are challenges with affordability and accessibility.

A review of interferon-free regimens for the treatment of patients with genotype 1 chronic HCV infection will help to inform treatment decisions for these patients.

Methods
A limited literature search was conducted of key resources, and titles and abstracts of the retrieved publications were reviewed. Full-text publications were evaluated for final article selection according to predetermined selection criteria (population, intervention, comparator, outcomes, and study designs).

Results
The literature search identified 545 citations, with 5 additional guidelines identified from other sources. After screening the abstracts, 28 were deemed potentially relevant and 10 met the criteria for inclusion in this review — 1 health technology assessment, 8 clinical trials (non-randomized and/or not controlled), and 1 economic evaluation.

Key Messages
Over 90% of patients had a sustained virologic response (SVR or “cure”) on these regimens:

  • sofosbuvir and ledipasvir, with or without ribavirin, for 8, 12, or 24 weeks*
  • sofosbuvir and daclatasvir, with or without ribavirin, for 12 or 24 weeks *
  • sofosbuvir and GS-9669 plus ribavirin for 12 weeks. *

SVR rates were lower for patients who only received sofosbuvir plus ribavirin. *

The incidence of serious side effects was low. Cost-effectiveness in a Canadian context was uncertain.

*These regimens are currently not approved in Canada.

Question

  1. What is the evidence for the clinical effectiveness and safety of boceprevir, simeprevir, sofosbuvir, and telaprevir interferon-free regimens?
  2. What is the cost-effectiveness of boceprevir, simeprevir, sofosbuvir, and telaprevir interferon-free regimens?

Key Message

The available evidence from the clinical trials indicates that sustained virological response (SVR) was achieved by more than 90% of patients who received sofosbuvir (SOF) and ledipasvir (LDV) with or without ribavirin (RBV) for 8, 12 or 24 weeks; SOF and daclatasvir (DCV) with or without RBV for 12 or 24 weeks; SOF and GS-9669 plus RBV for 12 weeks in treatment naïve and treatment experienced patients. Lower rates of SVR were reported in those who only received SOF plus RBV. Serious AEs and discontinuation due to AEs were low and anemia, rash and depression were low in patients who did not receive RBV. LDV, DCV and GS-9669 have not yet received Health Canada Notice of Compliance (NOC). Two economic evaluations conducted outside of Canada demonstrated that SOF plus simeprivir (SIM) is more cost-effective than SOF plus RBV. However, cost-effectiveness of SOF plus SIM in a Canadian population is uncertain.

Tags

hepatitis c, liver, hepatitis, IFN free, Incivek, Victrelis, Sovaldi, Galexos, genotype 1, genotype one