June 26, 2013

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Clinical Gastroenterology and Hepatology June 2013
Article in Press

HCV Care in VA Debated - (06/24/13)

Kee Chan, PhD1,2,3, Mai Ngan Lai, MD4, Erik J. Groessl, PhD4,5, Amresh D. Hanchate, PhD3,6, John B. Wong, MD 7, Jack A. Clark, PhD 3,6, Steven M. Asch, MD MPH8, Allen L. Gifford, MD3,6, and Samuel B. Ho, MD 4,5

1. Department of Health Sciences, College of Health and Rehabilitation Sciences: Sargent College, Boston University, Boston, MA
2. Department of Epidemiology, School of Public Health, Boston University, Boston, MA
3. VA HIV/Hepatitis Quality Enhancement Research Initiative, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA
4. VA San Diego Healthcare System, San Diego, CA
5. University of California, San Diego, San Diego, CA
6. Departments of Health Policy and Management, and Medicine, Boston University, Boston, MA
7. Division of Clinical Decision Making, Informatics, and Telemedicine, Tufts Medical Center, Boston, MA
8. HRS&D Center of Excellence and Research Service, VA Palo Alto Healthcare System, Palo Alto, CA

"In conclusion, our model indicates the upfront costs required for treatment with Boc/PR or Tel/PR are high; however the offsetting benefits of extending quality of life and lower costs due to liver-related morbidity indicate that these therapies have very acceptable incremental cost-effectiveness ratios compared to previous therapies in this managed care health care system. Further efforts to expand access to DAA therapy are warranted. In our study, we evaluated cost effectiveness of DAA treatment strategies in a defined managed care population with pharmaceutical pricing based on large group negotiated prices. In the future, integrated care systems may be more common with the evolution of the Affordable Care Act and similar heath care reforms38, and drug pricing advantages will play an important role in determining overall cost effectiveness of new medications. In addition, our data is more relevant to health care systems in other countries with similar large group negotiated prices.

Cost-effectiveness ratios are one very important, but not sufficient, factor for making health policy decisions. Other factors such as system adaptability, budgetary issues, and patient preferences should also be considered in addition to our findings. This model will continue to be of use to evaluate future DAA therapies for HCV treatment, which may demonstrate increased efficacy albeit with significant costs."

Abstract
Background and Aim

The Veterans Health Administration (VHA) is the largest single provider of care for hepatitis C virus (HCV) infection in the US. We analyzed the cost-effectiveness of treatment with the HCV protease inhibitors boceprevir and telaprevir in a defined managed care population of 102,851 patients with untreated chronic genotype 1 infection.

Methods

We used a decision-analytic Markov model to examine 4 strategies: standard dual-therapy with pegylated interferon-alfa and ribavirin (PR), the combination of boceprevir and PR triple therapy, the combination of telaprevir and PR, or no antiviral treatment; sensitivity analysis was performed. Sources of data included published rates of disease progression, the census bureau, and VHA pharmacy and hospitalization cost databases.

Results

The estimated costs for treating each patient were $8000 for PR, $31,300 for boceprevier and PR, and $41,700 for telaprevir and PR. Assuming VHA treatment rates of 22% and optimal rates of sustained viral response, PR, boceprevir and PR, and telaprevir and PR would reduce relative liver-related deaths by 5.2%, 10.9%, and 11.5%, respectively. Increasing treatment rates to 50% would reduce liver-related deaths by 12%, 24.7%, and 26.1%, respectively. The incremental cost-effectiveness ratios were $29,184/quality of adjusted-life years (QALY) for boceprevir and PR and $44,247/QALY for telaprevir and PR vs only PR. With the current 22% treatment rate, total system-wide costs to adopt boceprevir and PR or telaprevir and PR would range from $708 million to $943 million.

Conclusions

Despite substantial upfront costs of treating HCV-infected patients in the VHA with PR, or telaprevir and PR, each regimen improves quality of life and extends life expectancy, by reducing liver-related morbidity and mortality, and should be cost effective. Further efforts to expand access to direct-acting antiviral therapy are warranted.

EXCERPTS

RESULTS

Compared to no treatment, use of standard PR therapy in the patient population at the treatment rate of 22% previously achieved among VA patients initiated on antiviral therapy between 2000-20081, 19 will decrease overall liver-related mortality by 5.0% (Table 2 and Figure 2). In contrast, treatment with DAA triple therapies at this same treatment rate, assuming the highest expected SVR rates (Boc/PR 54 % and Tel/PR 57%), will result in a 10.4 to 11.0% reduction in liver related death, respectively. If a treatment rates with PR, Boc/PR or Tel/PR can be increased to 50% of patients, the long-term reduction liver-related deaths will be 11.4%, 23.7% and 25.0%, respectively.

Cost and cost-effectiveness of antiviral treatments

With the previously achieved inital treatment rate of 22 %, total system-wide costs to adopt Boc/PR or Tel/PR would be $708 million and $943 million, respectively. Increasing treatment rates to 50% would result in the total cost of antiviral therapies PR, Boc/PR and Tel/PR treatment to be $411 million, $1,610 million and $2,144 million, respectively (Figure 3). Without antiviral treatment, the expected total cost of care for hepatitis C-related liver disease is $3,729 million. Compared with no treatment using PR at a 50% treatment rate results in overall cost savings of $30 million over the VHA cohort lifetime. In contrast, using Boc/PR or Tel/PR at a 50% treatment rate results in net cost expenditures of $692 million or $1,175 million, respectively.

The estimated cost and effectiveness (QALY) for the average treatment-naïve genotype 1 VHA patient and the incremental cost effectiveness ratio of DAA triple therapies compared with no therapy and PR therapy are given in Table 3A. Assuming the higher estimated SVR rates, the ICER for BocPR vs. PR = $29,184/QALY gained and TelPR vs. PR = $44,247/QALY gained.

Erythropoetin use was considered optional in the Boc licensing trial and not used in Tel licensing trials, and no SVR data is available for patients treated with TelPR when erythropoietin is used. Table 3B demonstrates the changes in ICER for DAA and PR therapies if potential costs of erythropoietin are included, which is common in clinical practice, although not universal.

For comparison purposes, the corresponding ICERs calculated using the average wholesale prices for Ribavirin, Peginterferon alfa, Boceprevir and Telaprevir are listed in Supplemental Table 6. The cost effectiveness for the four treatment strategies based on patient age and fibrosis stage are listed in Supplemental Table 7, and indicate that treating subgroups with younger age and more advanced fibrosis stage will be more cost-effective. As of 2010 there were approximately 21,466 genotype 1 patients that failed previous interferon treatment in the VHA. There is little data available concerning treatment of prior PR treatment failures in VHA populations, therefore we have used data from published phase III trials to make preliminary estimates related to incremental cost effectiveness ratios of DAA re-treatment in this patient population (Technical Appendix and Supplemental Table 8) 14, 15, 32

DISCUSSION

Our model projects cost-effectiveness analysis of the new DAAs therapy in the veteran population. Our simulated cohort of 102,851 treatment-naïve US veteran patients with HCV genotype 1 infection had more than 2-fold reduction in liver related death when they were treated with either Boc/PR or Tel/PR strategies compared to treatment with PR alone. When we used VHA contract FSS pricing, the incremental cost effectiveness ratio (ICER) of Boc/PR and Tel/PR compared with PR are $29,184/QALY gained and $44,247/QALY gained, respectively. The ICER of Boc/PR and Tel/PR compared to no treatment are $15,027/QALY gained and $24,467/QALY gained, respectively. For patients in their 40's and 50's with early fibrosis stage 1 and 2, the ICERs for DAA treatments compared with PR are within the oft cited $50,000/QALY gained threshold for consideration of acceptable ICERs for medical interventions. Our results indicate that these therapies are cost-effective for the majority of US veteran patients.

Other recent studies have showed similar cost-effectiveness results using wholesale pricing of the new DAA therapy. Liu et al. used average wholesale pricing for DAA therapy of $1100 per week 33. They projected the ICER of triple therapy vs. dual therapy would be $102,600 for patients with mild fibrosis and $51,000 for patients with advanced fibrosis, which is considerably higher than our projected cost effectiveness as would be expected given their higher pharmaceutical costs. Strategies to improve the ICERs of HCV antiviral treatments in the community setting may include selecting patients (such as those with advanced fibrosis) who would be more likely to benefit from therapy. In addition, they evaluated the use of the strategy of IL28 genotyping to guide therapy, with IL28 CC genotypes receiving PR therapy first. IL28-guided triple therapy treatment strategy results in reduced ICER for triple therapy treatment, although reductions in lifetime decompensated cirrhosis and HCC obtained with this strategy were only approximately 83% of those achieved with universal triple therapy. Recent data has demonstrated that IL28 CC patients treated with Tel/PR for 12 weeks achieve a 100% SVR rate compared with 64% SVR for these patients treated with PR for 48 weeks34. These data appear to mitigate the benefits of an IL28-guided strategy and lessen the likelihood that this would be an acceptable clinical alternative, yet further efforts to select patients most likely to benefit would be warranted under these scenarios. Further comparisons and limitations of our study are listed in the Technical Appendix.

We accounted for uncertainties regarding DAA treatment by estimating a range of possible SVR rates based on SVR rates attained in the VHA population with dual therapy pegylated interferon alfa and ribavirin. A recent meta-analysis by Cooper et al. compared SVR rates of BocPR and TelPR based on all data from phase II and phase III trials using a network meta-analysis and indirect comparisons to relative risk for SVR, and resulted in similar results as our analysis using phase III trial data35. For estimating duration of therapy with DAA treatments we used data from registration trials to calculate the percentage of patients with early treatment discontinuation and the percentage eligible to receive shorter durations of therapy. Because data from the Boceprevir registration trial was reported for Non-black and Black populations separately, we adjusted the treatment duration estimates for the known Non-black and Black patient distribution in VHA HCV patients, and therefore this data may be more accurate than the estimated treatment durations obtained from the Telaprevir registration trial.

A critical question for health care systems is the percentage of patients that are able to receive current antiviral therapies. Our data reflects the optimistic treatment rate of 50%, with the potential consequence of a 24-25% reduction in liver-related deaths. Such treatment rates in a VHA population may be attained with the use of integrated care protocols, which have surpassed 40% of VHA patients with pre-existing risk factors for psychiatric and substance use conditions in a recent study36, 37. Future interferon-free regimens are likely necessary for maximizing the number of HCV patients that can receive antiviral therapy.

In conclusion, our model indicates the upfront costs required for treatment with Boc/PR or Tel/PR are high; however the offsetting benefits of extending quality of life and lower costs due to liver-related morbidity indicate that these therapies have very acceptable incremental cost-effectiveness ratios compared to previous therapies in this managed care health care system. Further efforts to expand access to DAA therapy are warranted. In our study, we evaluated cost effectiveness of DAA treatment strategies in a defined managed care population with pharmaceutical pricing based on large group negotiated prices. In the future, integrated care systems may be more common with the evolution of the Affordable Care Act and similar heath care reforms38, and drug pricing advantages will play an important role in determining overall cost effectiveness of new medications. In addition, our data is more relevant to health care systems in other countries with similar large group negotiated prices.

Cost-effectiveness ratios are one very important, but not sufficient, factor for making health policy decisions. Other factors such as system adaptability, budgetary issues, and patient preferences should also be considered in addition to our findings. This model will continue to be of use to evaluate future DAA therapies for HCV treatment, which may demonstrate increased efficacy albeit with significant costs.

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