Clinical Impact of Treatment Timing for Chronic HCV
Clinical Impact of Treatment Timing for Chronic HCV
Recent advances in the treatment of hepatitis C virus (HCV) infection have led to the availability of both highly efficacious interferon-containing and interferon-sparing regimens. However, the use of such therapies faces restrictions due to high costs. For patients who are medically eligible to receive interferon, the choice between the two will likely be impacted by preferences surrounding interferon, severity of disease, coverage policies and out-of-pocket costs. We developed a decision model to quantify the trade-offs between immediate, interferon-containing therapy and delayed, interferon-free therapy for patients with chronic, genotype 1 HCV infection. We projected the quality-adjusted life expectancy stratified by the presence or absence of cirrhosis for four strategies: (i) no treatment; (ii) immediate, one-time treatment with an interferon-containing regimen; (iii) immediate treatment as above with the opportunity for retreatment in patients who fail to achieve sustained virologic response with interferon-free therapy in 1 year; and (iv) delayed therapy with interferon-free therapy in 1 year. When compared to one-time immediate treatment with the interferon-containing regimen, delayed treatment with the interferon-free regimen in 1 year resulted in longer life expectancy, with a 0.2 quality-adjusted life year (QALY) increase in noncirrhotic patients, and a 1.1 QALY increase in patients with cirrhosis. This superiority in health benefits was lost when wait time for interferon-free therapy was greater than 3–3.2 years. In this modelling analysis, interferon-free therapy resulted in superior health benefits compared to immediate therapy with interferon until wait time exceeded 3–3.2 years. Such data can inform decision-making regarding treatment initiation for HCV as healthcare financing evolves.
Hepatitis C virus (HCV) has a high burden of disease globally, where more than 185 million persons are estimated to be living with chronic infection. Over time HCV causes cirrhosis in approximately 40% of individuals due to progressive liver fibrosis, a clinical condition that confers increased risk of hepatocellular cancer, variceal bleeding, hepatic failure and other complications of advanced liver disease. Liver-related morbidity and mortality is projected to increase substantially in the coming years, with an estimated 1.76 million persons with HCV developing cirrhosis and more than 1 million persons dying of liver disease by 2060 in the United States alone.
While the development of new, oral direct-acting antiviral medications (DAAs) has revolutionized the landscape of hepatitis C therapy, the high price tag has led to increasingly restrictive policies regarding coverage eligibility reported among various US state Medicaid programmes, including limiting access to those with advanced liver fibrosis. Internationally, the WHO has endorsed the use of DAAs, although price negotiations have varied between countries. As a result, many HCV-infected patients both now, and in the future, will face a decision of whether they would rather be treated immediately, with a less costly, interferon-containing regimen, or wait until such a time that they be considered eligible for an interferon-free treatment.
Deferring therapy until interferon-free options are accessible, however, is not without risk. Progressive liver disease as well as the development of hepatocellular cancer may increase morbidity and mortality in untreated individuals. Additionally, symptoms of HCV, such as malaise, fatigue and abdominal pain, might lower quality of life throughout the time that a patient is forced to wait for interferon-free therapy. The appropriate choice for any individual – treat now or wait? – is a complex function of expected mortality, treatment efficacy and quality of life.
In the light of rapid therapeutic advancement for HCV, data are needed to inform the decision-making between providers and patients regarding the health benefits and risk associated with waiting for interferon-free therapy. We used decision-analytic modelling to quantify the trade-offs between immediate, interferon-containing therapy and delayed, interferon-free therapy for patients with chronic, genotype 1 hepatitis C virus infection.
Abstract and Introduction
Abstract
Recent advances in the treatment of hepatitis C virus (HCV) infection have led to the availability of both highly efficacious interferon-containing and interferon-sparing regimens. However, the use of such therapies faces restrictions due to high costs. For patients who are medically eligible to receive interferon, the choice between the two will likely be impacted by preferences surrounding interferon, severity of disease, coverage policies and out-of-pocket costs. We developed a decision model to quantify the trade-offs between immediate, interferon-containing therapy and delayed, interferon-free therapy for patients with chronic, genotype 1 HCV infection. We projected the quality-adjusted life expectancy stratified by the presence or absence of cirrhosis for four strategies: (i) no treatment; (ii) immediate, one-time treatment with an interferon-containing regimen; (iii) immediate treatment as above with the opportunity for retreatment in patients who fail to achieve sustained virologic response with interferon-free therapy in 1 year; and (iv) delayed therapy with interferon-free therapy in 1 year. When compared to one-time immediate treatment with the interferon-containing regimen, delayed treatment with the interferon-free regimen in 1 year resulted in longer life expectancy, with a 0.2 quality-adjusted life year (QALY) increase in noncirrhotic patients, and a 1.1 QALY increase in patients with cirrhosis. This superiority in health benefits was lost when wait time for interferon-free therapy was greater than 3–3.2 years. In this modelling analysis, interferon-free therapy resulted in superior health benefits compared to immediate therapy with interferon until wait time exceeded 3–3.2 years. Such data can inform decision-making regarding treatment initiation for HCV as healthcare financing evolves.
Introduction
Hepatitis C virus (HCV) has a high burden of disease globally, where more than 185 million persons are estimated to be living with chronic infection. Over time HCV causes cirrhosis in approximately 40% of individuals due to progressive liver fibrosis, a clinical condition that confers increased risk of hepatocellular cancer, variceal bleeding, hepatic failure and other complications of advanced liver disease. Liver-related morbidity and mortality is projected to increase substantially in the coming years, with an estimated 1.76 million persons with HCV developing cirrhosis and more than 1 million persons dying of liver disease by 2060 in the United States alone.
While the development of new, oral direct-acting antiviral medications (DAAs) has revolutionized the landscape of hepatitis C therapy, the high price tag has led to increasingly restrictive policies regarding coverage eligibility reported among various US state Medicaid programmes, including limiting access to those with advanced liver fibrosis. Internationally, the WHO has endorsed the use of DAAs, although price negotiations have varied between countries. As a result, many HCV-infected patients both now, and in the future, will face a decision of whether they would rather be treated immediately, with a less costly, interferon-containing regimen, or wait until such a time that they be considered eligible for an interferon-free treatment.
Deferring therapy until interferon-free options are accessible, however, is not without risk. Progressive liver disease as well as the development of hepatocellular cancer may increase morbidity and mortality in untreated individuals. Additionally, symptoms of HCV, such as malaise, fatigue and abdominal pain, might lower quality of life throughout the time that a patient is forced to wait for interferon-free therapy. The appropriate choice for any individual – treat now or wait? – is a complex function of expected mortality, treatment efficacy and quality of life.
In the light of rapid therapeutic advancement for HCV, data are needed to inform the decision-making between providers and patients regarding the health benefits and risk associated with waiting for interferon-free therapy. We used decision-analytic modelling to quantify the trade-offs between immediate, interferon-containing therapy and delayed, interferon-free therapy for patients with chronic, genotype 1 hepatitis C virus infection.
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