1.A Model-Based Cost-Effectiveness Analysis of Long-Acting Monoclonal Antibody (Tixagevimab and Cilgavimab: Evusheld) Preventive Treatment for High-Risk Populations Against SARSCoV-2 in Korea
Youngji JO ; Sun Bean KIM ; Jaehun JUNG
Journal of Korean Medical Science 2023;38(32):e250-
Background:
Tixagevimab and cilgavimab (Evusheld) administration is a recommended strategy for unvaccinated patients with immunocompromised conditions and severe allergic reaction conditions to protect high-risk individuals and control the coronavirus disease 2019 (COVID-19) epidemic. We estimated the cost-effectiveness of Evusheld in key risk populations: 1) immunocompromised (vaccinated/unvaccinated), 2) severe allergic reaction, and 3) unvaccinated elderly high-risk groups.
Methods:
Based on the estimated target risk group population, we used a model of COVID-19 transmission to estimate the size of the risk group population for whom Evusheld treatment may help prevent symptomatic COVID-19 (and deaths) in 2022. We projected Evusheld intervention costs, quality-adjusted life year (QALY) lost, cost averted and QALY gained by reduced COVID-19 incidence, and incremental cost-effectiveness (cost per QALY gained) in each modeled population from the healthcare system perspective.
Results:
Our study demonstrated that Evusheld treatment for COVID-19 infection in South Korea is highly cost-effective for unvaccinated risk groups ($18,959 per QALY gained for immunocompromised and $23,978 per QALY gained for high-risk elderly groups) and moderately cost-effective among individuals who are vaccinated immunocompromised ($46,494 per QALY gained), or have severe allergic reactions ($45,996 per QALY gained).Evusheld’s cost-effectiveness may be subject to risk-group-specific COVID-19 disease progression and Evusheld efficacy and cost, which may change in future epidemic scenarios.
Conclusion
As the COVID-19 variants and risk group-specific durable efficacy, toxicity (and/ or resistance) and optimal dosing of Evusheld remain uncertain, better empirical estimates to inform these values in different epidemiological contexts are needed. These results may help decision-makers prioritize resources toward more equitable and effective COVID-19 control efforts.
2.Optimal Social Distancing Policy for COVID-19 Control in Korea:A Model-Based Analysis
Youngji JO ; Sourya SHRESTHA ; Munkhzul RADNAABAATAR ; Hojun PARK ; Jaehun JUNG
Journal of Korean Medical Science 2022;37(23):e189-
Background:
Since March 2020, when coronavirus disease 2019 (COVID-19) was declared a pandemic, many countries have applied unprecedented restrictive measures to contain the spread of the virus. This study aimed to explore the optimal social distancing policy for COVID-19 control in South Korea to safely reopen the society.
Methods:
We developed an age-specific, deterministic compartment epidemic model to examine the COVID-19 control decision-making process, including the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 July 2021 and 30 December 2022.The model consists of the natural history of COVID-19, testing performance, vaccinations, and social distancing enforcement measures to detect and control SARS-CoV-2. We modelled potential intervention scenarios with three distinct components: 1) social distancing duration and level;2) testing intensity; and 3) vaccination uptake rate. The primary and secondary outcomes were COVID-19 incidence and prevalence of severe patients requiring intensive care unit (ICU) care.
Results:
Four (or more) months of social distancing (that can reduce 40–60% transmission) may mitigate epidemic resurgence and ICU demand in the future and keep the cases below the capacity limit if the testing intensity and vaccination rate remain constant or increase by 20% (with respect to the current level). In contrast, two months of strict social distancing enforcement may also successfully mitigate future epidemic surge and ICU demand as long as testing intensity and vaccination rates are increased by 20%.
Conclusion
In South Korea, given the relatively high vaccination coverage and low incidence, four or more months of social distancing enforcement can effectively mitigate epidemic resurgence after lifting the social distancing measures. In addition, increasing the testing intensity and vaccination rate may help reduce necessary social distancing levels and duration to prevent a future epidemic resurgence and mitigate social and economic damage.
3.Model-based cost-effectiveness analysis of oral antivirals against SARS-CoV-2 in Korea
Youngji JO ; Sun Bean KIM ; Munkhzul RADNAABAATAR ; Kyungmin HUH ; Jin-Hong YOO ; Kyong Ran PECK ; Hojun PARK ; Jaehun JUNG
Epidemiology and Health 2022;44(1):e2022034-
OBJECTIVES:
Many countries have authorized the emergency use of oral antiviral agents for patients with mild-to-moderate cases of coronavirus disease 2019 (COVID-19). We assessed the cost-effectiveness of these agents for reducing the number of severe COVID-19 cases and the burden on Korea’s medical system.
METHODS:
Using an existing model, we estimated the number of people who would require hospital/intensive care unit (ICU) admission in Korea in 2022. The treatment scenarios included (1) all adult patients, (2) elderly patients only, and (3) adult patients with underlying diseases only, compared to standard care. Based on the current health system capacity, we calculated the incremental costs per severe case averted and hospital admission for each scenario.
RESULTS:
We estimated that 236,510 COVID-19 patients would require hospital/ICU admission in 2022 with standard care only. Nirmatrelvir/ritonavir (87% efficacy) was predicted to reduce this number by 80%, 24%, and 17% when targeting all adults, adults with underlying diseases, and elderly patients (25, 8, and 4%, respectively, for molnupiravir, with 30% efficacy). Nirmatrelvir/ritonavir use is likely to be cost-effective, with predicted costs of US$8,878, US$8,964, and US$1,454, per severe patient averted for the target groups listed above, respectively, while molnupiravir is likely to be less cost-effective, with costs of US$28,492, US$29,575, and US$7,915, respectively.
CONCLUSIONS
In Korea, oral treatment using nirmatrelvir/ritonavir for symptomatic COVID-19 patients targeting elderly patients would be highly cost-effective and would substantially reduce the demand for hospital admission to below the capacity of the health system if targeted to all adult patients instead of standard care.
4.Nationwide Target Trial Emulation Evaluating the Clinical Effectiveness of Oral Antivirals for COVID-19 in Korea
Kyungmin HUH ; Youngji JO ; Gi Hwan BAE ; Hyejin JOO ; Munkhzul RADNAABAATAR ; Hyungmin LEE ; Jungyeon KIM ; Dong-Hwi KIM ; Min-Gyu YOO ; Il Uk JO ; Poong Hoon LEE ; Geun Woo LEE ; Hee Sun JUNG ; Jaehun JUNG
Journal of Korean Medical Science 2024;39(42):e272-
Background:
Despite the proven effectiveness of oral antivirals against severe acute respiratory syndrome coronavirus 2 in randomized trials, their clinical reevaluation is vital in the context of widespread immunity and milder prevalent variants. This study aimed to assess the effectiveness of oral antivirals for coronavirus disease 2019 (COVID-19).
Methods:
This retrospective cohort study utilized a target trial emulation framework to analyze patients with COVID-19 aged 60+ from January to December 2022. Data were obtained from the Korea Disease Control and Prevention Agency and Health Insurance Review and Assessment Service. The study involved 957,036 patients treated with nirmatrelvir/ritonavir and 243,360 treated with molnupiravir, each compared with the matched control groups. Primary outcome was progression to critical COVID-19 requiring advanced respiratory support. Secondary outcomes included progression to severe COVID-19, need for supplemental oxygen, and death within 30 days of the onset of COVID-19.Number needed to treat (NNT) derived from the absolute risk reduction.
Results:
Nirmatrelvir/ritonavir was significantly associated with a reduced risk of severe (adjusted odds ratio [aOR], 0.823; 95% confidence interval [CI], 0.803–0.843), critical (aOR, 0.560; 95% CI, 0.503–0.624), and fatal COVID-19 (aOR, 0.694; 95% CI, 0.647–0.744).Similarly, molnupiravir reduced the risk of severe (aOR, 0.895; 95% CI, 0.856–0.937), critical (aOR, 0.672; 95% CI, 0.559–0.807), and fatal cases (aOR, 0.679; 95% CI, 0.592–0.779).NNTs for nirmatrelvir/ritonavir were 203.71 (severe), 1,230.12 (critical), and 691.50 (death);for molnupiravir, they were 352.70 (severe), 1,398.62 (critical), and 862.98 (death). Higher effectiveness was associated with older adults, unvaccinated individuals, and the late pandemic phase.
Conclusion
Nirmatrelvir/ritonavir and molnupiravir are effective in preventing progression to severe disease in elderly adults with COVID-19.
5.Nationwide Target Trial Emulation Evaluating the Clinical Effectiveness of Oral Antivirals for COVID-19 in Korea
Kyungmin HUH ; Youngji JO ; Gi Hwan BAE ; Hyejin JOO ; Munkhzul RADNAABAATAR ; Hyungmin LEE ; Jungyeon KIM ; Dong-Hwi KIM ; Min-Gyu YOO ; Il Uk JO ; Poong Hoon LEE ; Geun Woo LEE ; Hee Sun JUNG ; Jaehun JUNG
Journal of Korean Medical Science 2024;39(42):e272-
Background:
Despite the proven effectiveness of oral antivirals against severe acute respiratory syndrome coronavirus 2 in randomized trials, their clinical reevaluation is vital in the context of widespread immunity and milder prevalent variants. This study aimed to assess the effectiveness of oral antivirals for coronavirus disease 2019 (COVID-19).
Methods:
This retrospective cohort study utilized a target trial emulation framework to analyze patients with COVID-19 aged 60+ from January to December 2022. Data were obtained from the Korea Disease Control and Prevention Agency and Health Insurance Review and Assessment Service. The study involved 957,036 patients treated with nirmatrelvir/ritonavir and 243,360 treated with molnupiravir, each compared with the matched control groups. Primary outcome was progression to critical COVID-19 requiring advanced respiratory support. Secondary outcomes included progression to severe COVID-19, need for supplemental oxygen, and death within 30 days of the onset of COVID-19.Number needed to treat (NNT) derived from the absolute risk reduction.
Results:
Nirmatrelvir/ritonavir was significantly associated with a reduced risk of severe (adjusted odds ratio [aOR], 0.823; 95% confidence interval [CI], 0.803–0.843), critical (aOR, 0.560; 95% CI, 0.503–0.624), and fatal COVID-19 (aOR, 0.694; 95% CI, 0.647–0.744).Similarly, molnupiravir reduced the risk of severe (aOR, 0.895; 95% CI, 0.856–0.937), critical (aOR, 0.672; 95% CI, 0.559–0.807), and fatal cases (aOR, 0.679; 95% CI, 0.592–0.779).NNTs for nirmatrelvir/ritonavir were 203.71 (severe), 1,230.12 (critical), and 691.50 (death);for molnupiravir, they were 352.70 (severe), 1,398.62 (critical), and 862.98 (death). Higher effectiveness was associated with older adults, unvaccinated individuals, and the late pandemic phase.
Conclusion
Nirmatrelvir/ritonavir and molnupiravir are effective in preventing progression to severe disease in elderly adults with COVID-19.
6.Nationwide Target Trial Emulation Evaluating the Clinical Effectiveness of Oral Antivirals for COVID-19 in Korea
Kyungmin HUH ; Youngji JO ; Gi Hwan BAE ; Hyejin JOO ; Munkhzul RADNAABAATAR ; Hyungmin LEE ; Jungyeon KIM ; Dong-Hwi KIM ; Min-Gyu YOO ; Il Uk JO ; Poong Hoon LEE ; Geun Woo LEE ; Hee Sun JUNG ; Jaehun JUNG
Journal of Korean Medical Science 2024;39(42):e272-
Background:
Despite the proven effectiveness of oral antivirals against severe acute respiratory syndrome coronavirus 2 in randomized trials, their clinical reevaluation is vital in the context of widespread immunity and milder prevalent variants. This study aimed to assess the effectiveness of oral antivirals for coronavirus disease 2019 (COVID-19).
Methods:
This retrospective cohort study utilized a target trial emulation framework to analyze patients with COVID-19 aged 60+ from January to December 2022. Data were obtained from the Korea Disease Control and Prevention Agency and Health Insurance Review and Assessment Service. The study involved 957,036 patients treated with nirmatrelvir/ritonavir and 243,360 treated with molnupiravir, each compared with the matched control groups. Primary outcome was progression to critical COVID-19 requiring advanced respiratory support. Secondary outcomes included progression to severe COVID-19, need for supplemental oxygen, and death within 30 days of the onset of COVID-19.Number needed to treat (NNT) derived from the absolute risk reduction.
Results:
Nirmatrelvir/ritonavir was significantly associated with a reduced risk of severe (adjusted odds ratio [aOR], 0.823; 95% confidence interval [CI], 0.803–0.843), critical (aOR, 0.560; 95% CI, 0.503–0.624), and fatal COVID-19 (aOR, 0.694; 95% CI, 0.647–0.744).Similarly, molnupiravir reduced the risk of severe (aOR, 0.895; 95% CI, 0.856–0.937), critical (aOR, 0.672; 95% CI, 0.559–0.807), and fatal cases (aOR, 0.679; 95% CI, 0.592–0.779).NNTs for nirmatrelvir/ritonavir were 203.71 (severe), 1,230.12 (critical), and 691.50 (death);for molnupiravir, they were 352.70 (severe), 1,398.62 (critical), and 862.98 (death). Higher effectiveness was associated with older adults, unvaccinated individuals, and the late pandemic phase.
Conclusion
Nirmatrelvir/ritonavir and molnupiravir are effective in preventing progression to severe disease in elderly adults with COVID-19.
7.Nationwide Target Trial Emulation Evaluating the Clinical Effectiveness of Oral Antivirals for COVID-19 in Korea
Kyungmin HUH ; Youngji JO ; Gi Hwan BAE ; Hyejin JOO ; Munkhzul RADNAABAATAR ; Hyungmin LEE ; Jungyeon KIM ; Dong-Hwi KIM ; Min-Gyu YOO ; Il Uk JO ; Poong Hoon LEE ; Geun Woo LEE ; Hee Sun JUNG ; Jaehun JUNG
Journal of Korean Medical Science 2024;39(42):e272-
Background:
Despite the proven effectiveness of oral antivirals against severe acute respiratory syndrome coronavirus 2 in randomized trials, their clinical reevaluation is vital in the context of widespread immunity and milder prevalent variants. This study aimed to assess the effectiveness of oral antivirals for coronavirus disease 2019 (COVID-19).
Methods:
This retrospective cohort study utilized a target trial emulation framework to analyze patients with COVID-19 aged 60+ from January to December 2022. Data were obtained from the Korea Disease Control and Prevention Agency and Health Insurance Review and Assessment Service. The study involved 957,036 patients treated with nirmatrelvir/ritonavir and 243,360 treated with molnupiravir, each compared with the matched control groups. Primary outcome was progression to critical COVID-19 requiring advanced respiratory support. Secondary outcomes included progression to severe COVID-19, need for supplemental oxygen, and death within 30 days of the onset of COVID-19.Number needed to treat (NNT) derived from the absolute risk reduction.
Results:
Nirmatrelvir/ritonavir was significantly associated with a reduced risk of severe (adjusted odds ratio [aOR], 0.823; 95% confidence interval [CI], 0.803–0.843), critical (aOR, 0.560; 95% CI, 0.503–0.624), and fatal COVID-19 (aOR, 0.694; 95% CI, 0.647–0.744).Similarly, molnupiravir reduced the risk of severe (aOR, 0.895; 95% CI, 0.856–0.937), critical (aOR, 0.672; 95% CI, 0.559–0.807), and fatal cases (aOR, 0.679; 95% CI, 0.592–0.779).NNTs for nirmatrelvir/ritonavir were 203.71 (severe), 1,230.12 (critical), and 691.50 (death);for molnupiravir, they were 352.70 (severe), 1,398.62 (critical), and 862.98 (death). Higher effectiveness was associated with older adults, unvaccinated individuals, and the late pandemic phase.
Conclusion
Nirmatrelvir/ritonavir and molnupiravir are effective in preventing progression to severe disease in elderly adults with COVID-19.