All-Oral, Interferon-Free Treatment for Chronic Hepatitis C
All-Oral, Interferon-Free Treatment for Chronic Hepatitis C
Using the base case parameters in this model, a generalized all-oral treatment regimen was cost-effective compared to SOC for a cohort of 50-year-old, monoinfected, cirrhotic and noncirrhotic subjects with genotype 1, 2 and 3 HCV infections. The model was robust to changes in treatment duration, nontreatment-related medical costs and QALY estimates, but sensitive to all-oral drug costs as well as rates of treatment uptake and SVR for noncirrhotic subjects. The cost ceiling for all-oral drugs was dependent on the WTP threshold and ranged from $74 217 at a $50 000/QALY WTP to $112 653 at a $100 000/QALY WTP. Depending on their budgets and priorities, diverse stakeholders may choose different WTP thresholds, which will affect the price at which these drugs can remain cost-effective compared to SOC.
The higher cost and lower SVR rates associated with SOC treatment for genotype 1 offer greater opportunity for cost reduction and QALY improvements compared to genotypes 2 and 3. As a result, all-oral treatment was most cost-effective for genotype 1 subjects. Cost per QALY gained was minimized in younger cohorts, possibly due to lower initial fibrosis levels among younger subjects and longer life expectancy after SVR.
This analysis has certain limitations. Because clinical trials investigating all-oral drugs are ongoing, most parameters involved in all-oral treatment are not yet known and were estimated from expert opinion. As additional data become available for a more generalizable population of CHC subjects, these parameters may need to be re-evaluated.
In addition, this model assumed that a 50-year-old CHC-infected cohort exhibited the same initial fibrosis distribution as the overall CHC-infected population. Because this age group falls into the high-risk 1945–1964 birth cohort likely to have been infected 20–30 years ago, this assumption may underestimate the true proportion of late-stage fibrosis and cirrhosis. A model including a higher percentage of late-stage disease may yield higher estimates of cost-effectiveness for all-oral drugs. Model costs associated with CHC treatment and care were based on direct medical costs only.
Due to the uncertainty of many parameters contributing to all-oral treatment and SVR, this model was designed to be conservative, and cost-effectiveness of all-oral treatment could be higher than we have reported for several reasons. Our model excluded certain groups that may ultimately be eligible for all-oral treatment. Specifically, although SOC treatment has demonstrated the potential to reduce reinfection following liver transplant, our model does not account for posttransplant treatment. Similarly, it does not allow for treatment in those with HCC, which may be possible with all-oral drugs. Successful CHC treatment could allow some individuals with HCC to undergo cancer treatments for which they would otherwise be ineligible, potentially reducing HCC-related mortality and increasing cost-effectiveness of all-oral treatment. In addition, although clinical trial data demonstrate up to 90% SVR in some treatment-experienced subgroups, our model does not include treatment-experienced individuals, many of whom may be eligible for retreatment with all-oral drugs, Once evidence-based estimates for treatment eligibility and outcomes are available for these groups, future models should account for late-stage treatment and retreatment with all-oral drugs to determine whether their inclusion impacts cost-effectiveness.
It is also possible that post-SVR fibrosis regression rates will be higher following treatment with all-oral drugs than our model has estimated. Even with SOC treatment, some subjects have demonstrated cirrhosis reversal after SVR, which we did not account for in our model. The percentage of decompensated subjects treated with all-oral drugs may also be higher than we estimated due to tolerability of interferon-free regimens.
Finally, if advanced clinical trials confirm high expectations for SVR and tolerability of all-oral drugs, HCV screening efforts will likely intensify, and treatment uptake can be expected to increase from current low rates of 12–28%, Uptake could increase more markedly than we have estimated, resulting in greater cost-effectiveness for all-oral regimens. Factors contributing to uptake include clinician confidence in treatment outcomes, the possibility of direct treatment by primary care physicians (possibly reducing loss to follow-up at the specialist referral stage), lower rates of discontinuation due to side effects and more widespread screening.
Universal clinical HCV screening in the general population has been demonstrated to be cost-effective under multiple scenarios, and some researchers are investigating the feasibility and cost-effectiveness of targeted testing and treatment efforts in specific high prevalence populations such as prison inmates and high-risk birth cohorts, both to improve health and to curb further transmission. Because of the increased SVR and tolerability of interferon-free regimens, all-oral treatments can be expected to reduce CHC-related morbidity and mortality beyond what is possible with current treatment options. Once these drugs become available in the clinic, it will be possible to determine whether broader treatment eligibility and greater opportunities for early treatment due to more aggressive screening efforts will have further implications for their cost-effectiveness.
Discussion
Using the base case parameters in this model, a generalized all-oral treatment regimen was cost-effective compared to SOC for a cohort of 50-year-old, monoinfected, cirrhotic and noncirrhotic subjects with genotype 1, 2 and 3 HCV infections. The model was robust to changes in treatment duration, nontreatment-related medical costs and QALY estimates, but sensitive to all-oral drug costs as well as rates of treatment uptake and SVR for noncirrhotic subjects. The cost ceiling for all-oral drugs was dependent on the WTP threshold and ranged from $74 217 at a $50 000/QALY WTP to $112 653 at a $100 000/QALY WTP. Depending on their budgets and priorities, diverse stakeholders may choose different WTP thresholds, which will affect the price at which these drugs can remain cost-effective compared to SOC.
The higher cost and lower SVR rates associated with SOC treatment for genotype 1 offer greater opportunity for cost reduction and QALY improvements compared to genotypes 2 and 3. As a result, all-oral treatment was most cost-effective for genotype 1 subjects. Cost per QALY gained was minimized in younger cohorts, possibly due to lower initial fibrosis levels among younger subjects and longer life expectancy after SVR.
This analysis has certain limitations. Because clinical trials investigating all-oral drugs are ongoing, most parameters involved in all-oral treatment are not yet known and were estimated from expert opinion. As additional data become available for a more generalizable population of CHC subjects, these parameters may need to be re-evaluated.
In addition, this model assumed that a 50-year-old CHC-infected cohort exhibited the same initial fibrosis distribution as the overall CHC-infected population. Because this age group falls into the high-risk 1945–1964 birth cohort likely to have been infected 20–30 years ago, this assumption may underestimate the true proportion of late-stage fibrosis and cirrhosis. A model including a higher percentage of late-stage disease may yield higher estimates of cost-effectiveness for all-oral drugs. Model costs associated with CHC treatment and care were based on direct medical costs only.
Due to the uncertainty of many parameters contributing to all-oral treatment and SVR, this model was designed to be conservative, and cost-effectiveness of all-oral treatment could be higher than we have reported for several reasons. Our model excluded certain groups that may ultimately be eligible for all-oral treatment. Specifically, although SOC treatment has demonstrated the potential to reduce reinfection following liver transplant, our model does not account for posttransplant treatment. Similarly, it does not allow for treatment in those with HCC, which may be possible with all-oral drugs. Successful CHC treatment could allow some individuals with HCC to undergo cancer treatments for which they would otherwise be ineligible, potentially reducing HCC-related mortality and increasing cost-effectiveness of all-oral treatment. In addition, although clinical trial data demonstrate up to 90% SVR in some treatment-experienced subgroups, our model does not include treatment-experienced individuals, many of whom may be eligible for retreatment with all-oral drugs, Once evidence-based estimates for treatment eligibility and outcomes are available for these groups, future models should account for late-stage treatment and retreatment with all-oral drugs to determine whether their inclusion impacts cost-effectiveness.
It is also possible that post-SVR fibrosis regression rates will be higher following treatment with all-oral drugs than our model has estimated. Even with SOC treatment, some subjects have demonstrated cirrhosis reversal after SVR, which we did not account for in our model. The percentage of decompensated subjects treated with all-oral drugs may also be higher than we estimated due to tolerability of interferon-free regimens.
Finally, if advanced clinical trials confirm high expectations for SVR and tolerability of all-oral drugs, HCV screening efforts will likely intensify, and treatment uptake can be expected to increase from current low rates of 12–28%, Uptake could increase more markedly than we have estimated, resulting in greater cost-effectiveness for all-oral regimens. Factors contributing to uptake include clinician confidence in treatment outcomes, the possibility of direct treatment by primary care physicians (possibly reducing loss to follow-up at the specialist referral stage), lower rates of discontinuation due to side effects and more widespread screening.
Universal clinical HCV screening in the general population has been demonstrated to be cost-effective under multiple scenarios, and some researchers are investigating the feasibility and cost-effectiveness of targeted testing and treatment efforts in specific high prevalence populations such as prison inmates and high-risk birth cohorts, both to improve health and to curb further transmission. Because of the increased SVR and tolerability of interferon-free regimens, all-oral treatments can be expected to reduce CHC-related morbidity and mortality beyond what is possible with current treatment options. Once these drugs become available in the clinic, it will be possible to determine whether broader treatment eligibility and greater opportunities for early treatment due to more aggressive screening efforts will have further implications for their cost-effectiveness.