All-oral, Interferon-free Treatment for Chronic Hepatitis C

Cost-effectiveness Analyses

L. M. Hagan; Z. Yang; M. Ehteshami; R. F. Schinazi

Disclosures

J Viral Hepat 

In This Article

Abstract and Introduction

Abstract

Interferon-based standard of care treatments (SOC) for chronic hepatitis C are unable to provide high cure rates in certain subgroups of the infected population and can cause debilitating side effects. Clinical trials evaluating all-oral, interferon-free treatments have demonstrated high rates of sustained virologic response with no resistance or major adverse events in most populations. As these drug regimens move towards FDA approval, it will be important to assess their cost-effectiveness in addition to their clinical efficacy. A decision-analytic Markov model with a lifetime, societal perspective was used to evaluate the cost-effectiveness of a generalized all-oral drug regimen compared to SOC by modelling the progression of a 50-year-old, HCV-positive cohort through disease natural history and treatment. In base case analysis, all-oral treatment dominated SOC across a range of willingness-to-pay (WTP) thresholds with an incremental cost-effectiveness ratio (ICER) of US$44 514/quality-adjusted life year (QALY). In sensitivity analyses, the model was sensitive to all-oral drug costs as well as rates of SVR and treatment uptake among noncirrhotic subjects, but robust to variations in all other parameters. All-oral treatment was most cost-effective among genotype 1 subjects but remained cost-effective for genotypes 2 and 3 at WTP thresholds ≥$80 000/QALY. Quality-adjusted life years gained per dollar spent were maximized in younger treatment cohorts. Using this model, the degree of cost-effectiveness depended on the WTP threshold and the final cost set for approved drug combinations.

Introduction

Approximately 150 million people globally and 3.3 million in the United States (US) are chronically infected with hepatitis C virus (HCV).[1] Because most cases are asymptomatic, up to 75% of HCV-positive individuals in the US are unaware of their infection, often resulting in untreated progression to advanced fibrosis, cirrhosis, hepatocellular carcinoma (HCC) and premature death.[2]

Chronic hepatitis C (CHC)-related mortality and healthcare costs are expected to rise as infected individuals in the high-prevalence 1945–1964 birth cohort, most of whom were infected 20–30 years ago, progress towards cirrhosis and liver cancer.[3–5] In response to this trend and to the demonstrated cost-effectiveness of birth cohort-based HCV screening,[6] the Centers for Disease Control and Prevention (CDC) recently recommended universal one-time screening for adults in this age group. This announcement coincided with the first National Hepatitis Testing Day in the US on 19 May 2012.[7]

As these screening initiatives yield increased CHC diagnoses, development of curative, cost-effective treatments will be paramount.[8] Treatment has evolved rapidly since the discovery of HCV in 1989, demonstrating progressive improvement in cure rates measured by sustained virologic response (SVR). The first treatment available, injected interferon monotherapy, resulted in SVR for 10% of those treated. Sustained virologic response increased to 25% with the addition of ribavirin and to 45% with the substitution of pegylated interferon.[8,9] Current standard of care (SOC) treatment for viral genotypes 2 and 3, pegylated interferon plus ribavirin (combination therapy), achieves SVR in up to 80% of noncirrhotic individuals, but in only 43% of those with cirrhosis,[10,11] Genotype 1 infections, which account for approximately 73% of CHC cases in the US, have historically been more difficult to treat and require triple therapy with the addition of a protease inhibitor (boceprevir or telaprevir),[12,13] SVR rates with triple therapy reach 72% among noncirrhotic genotype 1 individuals but are still much lower (42%) among those with cirrhosis,[14,15]

Despite rising SVR rates, current treatment with interferon and ribavirin often causes debilitating flu-like symptoms, depression, skin rashes and anaemia that can undermine treatment completion.[2] The next major advance in CHC treatment is expected to be the adoption of all-oral regimens that eliminate interferon, and possibly ribavirin, using direct-acting antiviral agents that increase SVR by preventing selection of drug resistant viruses and leveraging the lack of latent phase in HCV replication.[16] Numerous pharmaceutical companies are sprinting towards the finish line in advanced stage clinical trials testing novel all-oral, interferon-free drug combinations, some of which have achieved SVR in more than 90% of some subgroups, including null and partial responders to prior interferon-based treatment.[17]

The final cost of these drugs will be unknown until they reach the market and may ultimately exceed the cost of SOC for some genotypes. In addition, because clinical trial results are based on relatively small sample sizes of carefully chosen subjects, they may overestimate the SVR rates that will be attained among a more diverse and representative population. Therefore, while data on costs and anticipated SVR remain in flux, it will be important to consider the cost-effectiveness of emerging all-oral treatments across multiple possible scenarios.

This analysis investigated the cost-effectiveness of all-oral CHC treatment compared to SOC using a range of potential drug costs, treatment-associated quality of life estimates and rates of SVR for genotypes 1, 2 and 3-infected, treatment-naïve subjects with and without cirrhosis. Because it is not yet certain which specific drug combination(s) will receive FDA approval, our model used a generalized all-oral regimen to determine the cost threshold at which these drugs would be cost-effective compared to SOC.

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