Cost-effectiveness of Sofosbuvir for Chronic HCV
Cost-effectiveness of Sofosbuvir for Chronic HCV
The efficacy of treatment for hepatitis C genotype 1 infection has significantly improved with the introduction of first-generation protease inhibitors. However, there remains a need for effective treatments for patients infected with other genotypes, for nonresponders and patients unsuitable for interferon. Sofosbuvir is the first nucleotide polymerase inhibitor with pan-genotypic activity. Sofosbuvir-based regimens have resulted in >90% sustained virological response across treatment-naïve genotype 1–6 patients in five phase III clinical trials of sofosbuvir administered with ribavirin or pegylated interferon and ribavirin. This analysis evaluates the cost-effectiveness of sofosbuvir within the current licensed indication, for genotype 1–6 in the UK. A Markov model followed a cohort of 10 000 patients over lifetime, with approximately 20% initiating treatment for compensated cirrhosis. Sofosbuvir-regimens were compared to telaprevir, boceprevir, pegylated interferon and ribavirin, or no treatment. Costs and outcomes were discounted at 3.5%. The cost perspective utilized costs applicable to the National Health Service in the UK. Sofosbuvir proved to be cost-effective in most patient populations with incremental cost-effectiveness ratios (ICERs) at £11 836/QALY and £7292/QALY against telaprevir and boceprevir, respectively. In genotype 3, sofosbuvir had a weighted ICER of £18 761/QALY. Sofosbuvir-based regimens are a cost-effective option for the majority of hepatitis C-infected patients in the United Kingdom although the incremental cost-effectiveness varies by genotype and regimen. Sofosbuvir and ribavirin is an alternative regimen for patients unsuitable for interferon.
Chronic hepatitis C (CHC) caused by the hepatitis C virus (HCV) is associated with significant hepatic and extra-hepatic morbidity and a significant societal health economic burden. Approximately 75–85% of patients progress to develop CHC, which is largely asymptomatic in the early stages of chronic disease. CHC patients are at a greater risk of developing cirrhosis, end stage liver disease or hepatocellular carcinoma (HCC). Over a period of 20 years, it is estimated that 10–15% of CHC patients eventually develop cirrhosis. Of these, an estimated 1–4% of patients develop HCC.
In the UK, it is estimated that approximately 215 000 individuals are chronically infected with HCV. Although, the incidence of HCV infection in the UK is declining, due to the lag time between the infection and disease, the future disease burden attributable to HCV remains considerable. It is estimated that if left untreated, 15 840 individuals in England alone will be living with cirrhosis or HCC by 2020, with more than 4200 requiring a liver transplant (LT). A recent study showed that the economic burden from CHC in patients achieving a sustained virological response (SVR) following antiviral therapy is substantially lower than in nonresponders (£190 vs £2530). This study estimated costs derived from the UK National Health Service (NHS) payer perspective for genotype (GT) 1 patients treated with pegylated interferon and ribavirin (PEG-INF + RBV).
Seven genotypes and several subtypes of HCV have been identified. In England, the most common genotypes of HCV are GT1 and GT3, accounting for nearly 90% of all HCV infections.
The nature and duration of INF-treatment varies according to GT, stage of disease and prior response. In the UK, current treatment options include dual therapy (PEG-INF + RBV) and triple therapy (protease inhibitor ((PI); telaprevir or boceprevir in combination with PEG-INF + RBV). Dual therapy is the standard of care (SOC) for GTs 2 and 3 and triple therapy for GT1.
Triple therapy has improved SVR rates for treatment-naïve (TN) or treatment-experienced (TE) GT1 patients. However, treatment remains suboptimal for many patients, and INF is unsuitable for patients contraindicated or intolerant to INF therapy. Treatment efficacy is also influenced by the presence of cirrhosis and patient's prior treatment status. It is estimated that of all diagnosed HCV patients, approximately 20% actually commence treatment and only 3–4% of the total diagnosed population achieves SVR. Current therapies are also associated with a range of limitations including long and complex treatment regimens, severe side-effects that have led to treatment discontinuations in real-world settings (>20–30%), and the development of treatment-resistant viral mutations, all of which can lead to treatment failure.
Thus, there is a clear medical need for more effective pan-genotypic regimens with a high barrier to resistance without drug-to-drug interactions that would enable a broader population of patients the possibility of cure.
Sofosbuvir (SOF) is the first nucleotide polymerase inhibitor with pan-genotypic activity and a high barrier to resistance. The European Medicines Agency has approved SOF in combination with RBV with or without PEG-INF, for 12 or 24 weeks according to the genotype for the treatment of adult CHC patients. It is the first INF-free, all-oral treatment option to be approved for patients unsuitable for INF (UI) and is also licensed for the treatment of human immunodeficiency virus (HIV) co-infected patients. The safety profile of SOF provides the opportunity of a cure for patients with decompensated cirrhosis (DCC), including those awaiting transplant. In view of the superior efficacy and safety profile, SOF has been recommended by the European Association for the Study of the Liver (EASL) as the preferred backbone treatment for all major genotypes in both mono-infected and HIV co-infected patients.
This analysis assessed the cost-effectiveness of SOF regimens for the following HCV mono-infected patient groups:
Abstract and Introduction
Abstract
The efficacy of treatment for hepatitis C genotype 1 infection has significantly improved with the introduction of first-generation protease inhibitors. However, there remains a need for effective treatments for patients infected with other genotypes, for nonresponders and patients unsuitable for interferon. Sofosbuvir is the first nucleotide polymerase inhibitor with pan-genotypic activity. Sofosbuvir-based regimens have resulted in >90% sustained virological response across treatment-naïve genotype 1–6 patients in five phase III clinical trials of sofosbuvir administered with ribavirin or pegylated interferon and ribavirin. This analysis evaluates the cost-effectiveness of sofosbuvir within the current licensed indication, for genotype 1–6 in the UK. A Markov model followed a cohort of 10 000 patients over lifetime, with approximately 20% initiating treatment for compensated cirrhosis. Sofosbuvir-regimens were compared to telaprevir, boceprevir, pegylated interferon and ribavirin, or no treatment. Costs and outcomes were discounted at 3.5%. The cost perspective utilized costs applicable to the National Health Service in the UK. Sofosbuvir proved to be cost-effective in most patient populations with incremental cost-effectiveness ratios (ICERs) at £11 836/QALY and £7292/QALY against telaprevir and boceprevir, respectively. In genotype 3, sofosbuvir had a weighted ICER of £18 761/QALY. Sofosbuvir-based regimens are a cost-effective option for the majority of hepatitis C-infected patients in the United Kingdom although the incremental cost-effectiveness varies by genotype and regimen. Sofosbuvir and ribavirin is an alternative regimen for patients unsuitable for interferon.
Introduction
Chronic hepatitis C (CHC) caused by the hepatitis C virus (HCV) is associated with significant hepatic and extra-hepatic morbidity and a significant societal health economic burden. Approximately 75–85% of patients progress to develop CHC, which is largely asymptomatic in the early stages of chronic disease. CHC patients are at a greater risk of developing cirrhosis, end stage liver disease or hepatocellular carcinoma (HCC). Over a period of 20 years, it is estimated that 10–15% of CHC patients eventually develop cirrhosis. Of these, an estimated 1–4% of patients develop HCC.
In the UK, it is estimated that approximately 215 000 individuals are chronically infected with HCV. Although, the incidence of HCV infection in the UK is declining, due to the lag time between the infection and disease, the future disease burden attributable to HCV remains considerable. It is estimated that if left untreated, 15 840 individuals in England alone will be living with cirrhosis or HCC by 2020, with more than 4200 requiring a liver transplant (LT). A recent study showed that the economic burden from CHC in patients achieving a sustained virological response (SVR) following antiviral therapy is substantially lower than in nonresponders (£190 vs £2530). This study estimated costs derived from the UK National Health Service (NHS) payer perspective for genotype (GT) 1 patients treated with pegylated interferon and ribavirin (PEG-INF + RBV).
Seven genotypes and several subtypes of HCV have been identified. In England, the most common genotypes of HCV are GT1 and GT3, accounting for nearly 90% of all HCV infections.
The nature and duration of INF-treatment varies according to GT, stage of disease and prior response. In the UK, current treatment options include dual therapy (PEG-INF + RBV) and triple therapy (protease inhibitor ((PI); telaprevir or boceprevir in combination with PEG-INF + RBV). Dual therapy is the standard of care (SOC) for GTs 2 and 3 and triple therapy for GT1.
Triple therapy has improved SVR rates for treatment-naïve (TN) or treatment-experienced (TE) GT1 patients. However, treatment remains suboptimal for many patients, and INF is unsuitable for patients contraindicated or intolerant to INF therapy. Treatment efficacy is also influenced by the presence of cirrhosis and patient's prior treatment status. It is estimated that of all diagnosed HCV patients, approximately 20% actually commence treatment and only 3–4% of the total diagnosed population achieves SVR. Current therapies are also associated with a range of limitations including long and complex treatment regimens, severe side-effects that have led to treatment discontinuations in real-world settings (>20–30%), and the development of treatment-resistant viral mutations, all of which can lead to treatment failure.
Thus, there is a clear medical need for more effective pan-genotypic regimens with a high barrier to resistance without drug-to-drug interactions that would enable a broader population of patients the possibility of cure.
Sofosbuvir (SOF) is the first nucleotide polymerase inhibitor with pan-genotypic activity and a high barrier to resistance. The European Medicines Agency has approved SOF in combination with RBV with or without PEG-INF, for 12 or 24 weeks according to the genotype for the treatment of adult CHC patients. It is the first INF-free, all-oral treatment option to be approved for patients unsuitable for INF (UI) and is also licensed for the treatment of human immunodeficiency virus (HIV) co-infected patients. The safety profile of SOF provides the opportunity of a cure for patients with decompensated cirrhosis (DCC), including those awaiting transplant. In view of the superior efficacy and safety profile, SOF has been recommended by the European Association for the Study of the Liver (EASL) as the preferred backbone treatment for all major genotypes in both mono-infected and HIV co-infected patients.
This analysis assessed the cost-effectiveness of SOF regimens for the following HCV mono-infected patient groups:
GT1: TN INF eligible (IE) or UI patients.
GTs 2 and 3: TN or TE patients who are IE or UI.
GT4/5/6:TN IE patients.
Source...