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(Cost Effectiveness) Impact of Interferon Free Regimens on Clinical and Cost Outcomes for Chronic Hepatitis C Genotype 1 Patients
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Jnl of Hepatology Article In Press Nov 2013
"This is the first study to investigate cost effectiveness of an IFN-free regimen for the treatment of patients with genotype 1 CH-C. Using a decision analytic Markov model, the results of this study demonstrated
that an IFN-free oral regimen for 12 weeks was the most cost effective treatment choice for this cohort of patients. Further, oral therapy for all G1-HCV patients without staging seems to be superior over the current standard of IFN-based triple therapy after staging for G1-HCV patients. Furthermore, IFN-free without staging was more cost effective than oral IFN-free regimen after staging. In fact, our sensitivity analyses showed that the cost of staging itself has no impact on cost-effectiveness of this regimen. This study suggests that with the development of highly effective IFN-free regimens with high SVR rates, low side effects and shorter duration, decision to treat or not to treat should not be based on the stage of liver disease. Nevertheless, the issue of staging remains important for other management issues in patients with liver disease such as screening for HCC or varices.
In this study, effectiveness, as measured in QALYs, also favored the oral IFN-free regimen for all with a mean effectiveness of 18.360 QALYs, followed by oral interferon free after staging at 17.505, triple therapy for all at 17.189, followed by treating with triple therapy after staging at 16.376."
"In summary, our data shows that oral IFN free therapy for all HCV-G1 patients reduced the number of patients developing advanced liver disease and increased life expectancy. Additionally, this therapeutic
choice may be the most cost-effective approach for treating HCV GT 1 patients. Further, these findings, combined with prior studies addressing the cohort of patients that should be screened, helps to establish a potential guideline for working with the general population in the identification of patients with HCV.
Nevertheless, the efficacy and safety of these IFN-free regimens must be fully confirmed using phase III randomized controlled trials."
"proportion of patients progressing to cirrhosis may increase from 25% as of 2010 to 37% by 2020......2010 through 2019, 165,900 deaths from chronic liver disease, 27,200 deaths from hepatocellular carcinoma, and $10.7 billion in direct medical expenditures for HCV will occur. During this same period, HCV may lead to 720,700 years of decompensated cirrhosis and hepatocellular carcinoma and to the loss of 1.83 million years of life in those younger than 65 at a societal cost of $21.3 and $54.2 billion, respectively......Through Markov modeling simulation, this analysis' aim was to determine the cost-effectiveness of IFN-containing versus IFN-free regimens for patients infected with HCV genotype 1. We assessed the impact of treatment decision based on stage of liver disease (staging-guided) versus treat all on the cost-effectiveness of these regimens."
"Cost of oral therapy was unavailable since these treatments are currently unapproved. The baseline cost of oral therapy was calibrated such that the average total treatment cost of oral therapy was equal to the average total treatment cost of triple therapy, despite the shorter duration of oral therapy. This resulted in a baseline cost of oral therapy of $5,800 per week. We also considered the scenario where this baseline cost was increased by 50% to $8,700 per week. All costs were expressed in 2012 US dollars."
"Based on the simulation model of 50,000 patients, the regimen with oral therapy after staging had the lowest mean total cost at $77,133 followed by the regimen of oral therapy for all at $90,681, triple IFN-containing therapy after staging at $93,981 and triple IFN containing therapy for all at $106,554. Effectiveness, as measured in QALYs, also favored the oral therapies with oral all having a mean effectiveness of 18.391 QALYs, followed by oral after staging at 17.529, triple therapy for all at 17.201
and triple therapy after staging at 16.386."
"Incremental Cost Effectiveness Analysis:
The incremental cost-effectiveness analysis showed that at the baseline cost of oral therapy, both triple therapy strategies were dominated by oral all and oral after staging, having both higher cost and lower effectiveness (Table 4A). Compared to oral regimen after staging, oral regimen for all patients had an incremental cost-effectiveness ratio (ICER) of $15,709/QALY. Increasing the cost of oral therapy by 50% of the baseline led to triple therapy after staging being the least costly option, while triple therapy for all remained dominated by oral regimen (Table 4B). However, because of superior outcomes, oral therapies remained cost-effective. Compared to the current standard treatment (triple therapy after staging for G1),
oral regimen after staging had an ICER of just $8,611/QALY. However, oral regimen for all HCV-G1 was still the most cost-effective strategy with an ICER of $25,109/QALY, which is still well below all commonly used thresholds of cost-effectiveness ($50,000/QALY)."
Article in Press
(Cost Effectiveness) Impact of Interferon Free Regimens on Clinical and Cost Outcomes for Chronic Hepatitis C Genotype 1 Patients
Journal of Hepatology Nov 2013
Zobair M. Younossi 1,3 Mendel E. Singer 2 Heshaam M. Mir 1,3 Linda Henry 3 Sharon Hunt 3
1 Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church VA, USA.
2 Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland OH, USA.
3 Betty & Guy Beatty Center for Integrated Research, Inova Health System, Falls Church VA, USA.
Abstract
Hepatitis C (HCV) is a common cause of chronic liver disease worldwide. Current standard treatment for genotype-1 patients uses a triple combination of pegylated-interferon alpha (IFN), ribavirin (RBV) and a direct-acting antiviral agent (DAA) with 75-80% sustained virologic response (SVR) rates.
Aim
Determine cost-effectiveness of staging-guided versus treat all HCV genotype-1 patients with interferon-based versus interferon-free regimens.
Methods
A decision analytic Markov model simulating patients until death compared four strategies for treating HCV genotype-1: Triple therapy (IFN, RBV, DAA) with staging-guidance or treat all and oral IFN-free regimen with staging-guidance or treat all. Strategies with staging initiated treatment at fibrosis stages F2-F4, with staging repeated every 5 years until age 70. The reference case was a treatment-naïve 50-year-old. Analysis was repeated for 50% increase in cost of oral therapy. Effectiveness was measured in quality-adjusted life years (QALYs).
Results
Treat all patients with oral IFN-free regimen was the most cost-effective strategy, with an ICER of $15,709/QALY at baseline cost of oral therapy. The ICER remained below $50,000/QALY in sensitivity analyses for baseline and +50% cost of oral therapy scenarios. The treat all strategy was also the most effective strategy; associated with the lowest risk of developing advanced liver disease.
Conclusions
Treating all HCV patients with oral IFN-free regimen reduced the number of patients developing advanced liver disease and increased life expectancy. Additionally, IFN-free regimen without staging may be the most cost-effective approach for treating HCV genotype-1 patients. The efficacy and safety of these regimens must be confirmed using randomized clinical trials.
Introduction
There are approximately 130 - 200 million people infected with the hepatitis C virus (HCV) worldwide [1, 2]. In comparison to human immunodeficiency virus (HIV), HCV is a more prevalent and yet a less diagnosed viral infection [3]. One of the important reasons for this discrepancy is the gap in knowledge amongst health care workers, social service providers, and other stakeholders about the extent, seriousness and total disease burden associated with HCV [4].
Progression of HCV-related liver disease is variable and associated with factors including duration of infection, age, male gender, obesity and type 2 diabetes, consumption of alcohol, and HIV co-infection [5, 6]. If left untreated, the median expected time to cirrhosis is 30 years. It is estimated that approximately a third of those infected are expected to develop cirrhosis within 20 years [1-6]. Assuming there are no changes in the standard of care for CH-C, the total number of patients who will develop advanced liver disease in 20 years is projected to increase 4-fold [7]; while the proportion of patients progressing to cirrhosis may increase from 25% as of 2010 to 37% by 2020 [8]. Finally, a recently validated forecasting model for HCV related morbidity and mortality in the U.S. has estimated that over the next 50 years, out of the population of the untreated CH-C without cirrhosis, 1.76 million people will develop cirrhosis, 418,000 will develop liver cancer, and 1,071,000 will die from cirrhosis related complications [9]. Similarly, another study estimated that from the year 2010 through 2019, 165,900 deaths from chronic liver disease, 27,200 deaths from hepatocellular carcinoma, and $10.7 billion in direct medical expenditures for HCV will occur. During this same period, HCV may lead to 720,700 years of decompensated cirrhosis and hepatocellular carcinoma and to the loss of 1.83 million years of life in those younger than 65 at a societal cost of $21.3 and $54.2 billion, respectively [10].
Although the burden of CH-C is astounding, effective treatment (sustained virologic response) does lead to cure and is shown to improve outcomes, specifically by decreasing morbidities and mortality in patients with advanced liver disease. In fact, sustained virologic response (SVR) has now been shown to be durable and reduce all- cause mortality and cirrhosis-related complications among patients infected with HCV [11,12, 13].
Historically, treatment of CH-C genotype 1 with pegylated interferon and ribavirin was associated with an SVR rate of approximately 45% in previously untreated patients. In 2011, the FDA approved two inhibitors of the non-structural protein 3/4A protease- telaprevir (TVR) and boceprevir (BOC).
These drugs are
used in combination with pegylated-interferon (IFN) and ribavirin (RBV) with a SVR rate of 75% in treatment-naïve HCV genotype (GT)-1 patients [14,15]. Despite these gains, challenges of these regimens related to side effects limit their widespread use [14,15]. Additionally, a complex dosing schedule (DAA taken three times daily and RBV taken two times daily) with a heavy daily pill burden (17-18 pills on BOC regimen, 11-12 pills on TVR regimen) make patient adherence difficult. Finally, drugs with the potential to interact with TVR and BOC are frequently prescribed for patients with HCV [14,15]. In fact, a recent report from a large community trial suggested significant side effects associated with these regimens in patients with HCV related cirrhosis [16]. On the other hand, patients with HCV and advanced fibrosis are precisely those patients who are at the most urgent need for treatment. In order to establish stage of hepatic fibrosis prior to treatment of chronic hepatitis C patients with genotype 1, historically, clinicians have required staging of liver disease through a liver biopsy. This treatment decision guided by the stage of liver disease for HCV genotype 1 has been recommended to target only those who could potentially benefit the most as well as to minimize the side effects. One of the reasons for this recommendation was related to the relatively low efficacy of anti-HCV treatment and/or the substantial side effects associated with interferon-based therapy. In fact, given the high efficacy and relatively short duration of treatment for HCV genotypes 2 and 3, biopsy-guided treatment for CH-C patients with G2 and G3 has not been used. In the era of highly effective antiviral regimens for HCV genotype 1 with higher efficacy and better side effect profile, the value of biopsy-guided treatment becomes questionable. In contrast, the issue of staging for all HCV patients, regardless of the treatment decision, remains important for other management needs such as screening for hepatocellular carcinoma (HCC) and varicose.
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