An estimated 250,000 Canadians have chronic hepatitis C virus (HCV) infection; however, the exact number affected is not known, as 30% to 70% of patients are unaware that they have been infected and limited population level surveillance has been carried out in Canada to document prevalent cases. While the incidence of HCV infection in the US and Canada appears to be stable or declining, liver-related morbidity and mortality are expected to increase over the coming decades, as those who are already infected age and develop progressive liver disease.
Since the early 2000s, pegylated interferon plus ribavirin (PR) has been the standard therapy for chronic hepatitis C (CHC). When effective, treatment leads to viral eradication or sustained virologic response (SVR), which is a virologic cure of infection, associated with improved long-term clinical outcomes. In patients with advanced fibrosis or cirrhosis at baseline, SVR is associated with reduced liver-related and all-cause mortality as well as a reduced incidence of liver failure and liver cancer. Although treatment with PR results in SVR in a proportion of patients, the treatment is less than ideal because of its long duration, numerous associated side effects, and relatively low efficacy. In 2011, the first two direct-acting antiviral (DAA) agents, boceprevir and telaprevir, were approved for use in combination with PR for patients with genotype 1 CHC. Recently, two new DAA agents (simeprevir and sofosbuvir) have been approved by Health Canada for use in patients with genotype 1 CHC, in combination with PR therapy.
Given the market entry of two new DAA agents, there is a need to determine the relative effectiveness, safety, and cost-effectiveness of approved treatments for genotype 1 CHC. Genotype 1 CHC is the most prevalent form of CHC infection in Canada, and it is also the least responsive to PR treatment. Despite the availability of boceprevir and telaprevir, a substantial unmet need remains. The treatment burden is high for regimens that require 48 weeks of therapy, and for treatment regimens that include PR. Patients have expressed the need for new treatments that have higher cure rates, better side effect profiles and reduced treatment burden, yet remain affordable and accessible. The introduction of the new DAA agents (simeprevir and sofosbuvir) may address some unmet needs through potentially higher cure rates, more favourable adverse event profiles, shorter treatment durations, or combinations of these. However, treatment costs remain a concern.
This review was undertaken to address policy questions put forward by the public drug plans in Canada (excluding Quebec), as described in the Therapeutic Review protocol. Specifically, this review is meant to inform formulary listing decisions for the four DAA therapies for the treatment of CHC genotype 1 by identifying the most cost-effective strategies, based on patient characteristics and prior treatment history. Key patient characteristics examined include liver fibrosis severity, genotype subtype, and HCV Q80K polymorphism (an amino acid substitution associated with resistance to simeprevir and possibly other protease inhibitors).
Copyright © CADTH 2014.