Cost-effectiveness of antiviral treatment in adult patients with immune-tolerant phase chronic hepatitis B.

OBJECTIVE: The cost-effectiveness of antiviral treatment in adult immune-tolerant (IT) phase chronic hepatitis B (CHB) patients is uncertain. DESIGN: We designed a Markov model to compare expected costs and quality-adjusted life-years (QALYs) of starting antiviral treatment at IT-phase ('treat-IT') vs delaying the therapy until active hepatitis phase ('untreat-IT') in CHB patients over a 20-year horizon. A cohort of 10 000 non-cirrhotic 35-year-old patients in IT-phase CHB (hepatitis B e antigen-positive, mean serum hepatitis B virus (HBV) DNA levels 7.6 log10 IU/mL, and normal alanine aminotransferase levels) was simulated. Input parameters were obtained from previous studies at Asan Medical Center, Korea. The incremental cost-effectiveness ratio (ICER) between the treat-IT and untreat-IT strategies was calculated. RESULTS: From a healthcare system perspective, the treat-IT strategy with entecavir or tenofovir had an ICER of US$16 516/QALY, with an annual hepatocellular carcinoma (HCC) incidence of 0.73% in the untreat-IT group. With the annual HCC risk ≥0.54%, the treat-IT strategy was cost-effective at a willingness-to-pay threshold of US$20 000/QALY. From a societal perspective considering productivity loss by premature death, the treat-IT strategy was extremely cost-effective, and was dominant (ICER <0) if the HCC risk was ≥0.43%, suggesting that the treat-IT strategy incurs less costs than the untreat-IT strategy. The most influential parameters on cost-effectiveness of the treat-IT strategy were those related with HCC risk (HBV DNA levels, platelet counts and age) and drug cost. CONCLUSION: Starting antiviral therapy in IT phase is cost-effective compared with delaying the treatment until the active hepatitis phase in CHB patients, especially with increasing HCC risk, decreasing drug costs and consideration of productivity loss.

Magnetic Resonance Imaging Is Cost-Effective for Hepatocellular Carcinoma Surveillance in High-Risk Patients With Cirrhosis.

Ultrasonography (US) is generally recommended for the surveillance of hepatocellular carcinoma (HCC) in patients at risk. However, in patients with cirrhosis who have sufficiently high HCC incidence, surveillance using magnetic resonance imaging (MRI) with liver-specific contrast showed markedly higher sensitivity in detecting early-stage HCC than US. This study aimed to compare the cost-effectiveness of semiannual surveillance using MRI versus US in patients with compensated cirrhosis and to identify the population that would gain optimal cost-effectiveness through MRI surveillance. We designed a Markov model to compare the expected costs and quality-adjusted life-years (QALYs), between MRI and US, with a 20-year time horizon, from the health care system perspective. The starting age of the cohort was 50 years, and 71% had hepatitis B virus-associated cirrhosis. The cycle length was 6 months. Transition probabilities and costs were obtained mainly from a prospective cohort study (the PRIUS study, NCT01446666). Cost and effectiveness were discounted at 5%. An incremental cost-effectiveness ratio (ICER) was calculated and tested using sensitivity analyses. The cost-effectiveness analysis indicated that the use of MRI incurred $5,562 incremental costs, 0.384 incremental life-years (LYs), and 0.221 incremental QALYs compared to US. The annual HCC incidence was the most influential factor on the ICER. The ICERs were $14,474/LY and $25,202/QALY at an annual HCC incidence of 3%. When the HCC incidence rate was >1.81%, the ICER was below $50,000/QALY. With increased HCC incidence, MRI surveillance was acceptable as a cost-effective option, even with an increased MRI/US cost ratio. Conclusion: Semiannual surveillance using MRI with liver-specific contrast may be more cost-effective than US in patients with virus-associated compensated cirrhosis at sufficiently high HCC risk despite the higher test cost of MRI.

The economic impact of disease progression and death in hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer patients: using Korean nationwide health insurance claims data.

OBJECTIVES: Recognizing the value of anticancer treatments based on progression-free survival and overall survival may help decision making in healthcare policy. We aimed to measure and compare the impact of disease progression and terminal state prior to death on healthcare costs in HR+, HER2- ABC patients. METHODS: We conducted a retrospective study using Korean nationwide health insurance claims database between 1 September 2012 and 31 August 2017. The impact of disease progression was estimated by measuring the average incremental monthly cost per patient during 1 year after progression compared to 1 year before progression. Death-related costs per patient per month (PPPM) were measured for those who died within 1 year after progression. Generalized estimating equation (GEE) was used to estimate the variations in PPPM costs by progression and death with adjustment for clinical factors. RESULTS: After progression, 1,636 patients expensed $2,892 per month more on average than before progression ($3762 vs. $870). The GEE analysis with adjustment for baseline characteristics showed that PPPM costs increased by 3.46 folds (95% CI = 3.06-3.93) after progression. Also, PPPM costs were 1.74 (95%CI = 1.43-2.12) times higher in patients who died within 1 year after progression relative to survived patients. When considering the interaction between progression and death, deceased patients showed higher increased ratio of PPPM costs after progression (4.91; p=value<.0001) than survived patients (2.95; 95% CI = 2.61-3.34). CONCLUSIONS: From the payer's perspective, more healthcare costs incurred during the progression state than terminal state in HR+, HER2- ABC patients. The impact of disease progression emphasizes the importance of effectively treating HR+, HER2- ABC patients.

Economic burden of subsequent fracture in osteoporosis patients in South Korea.

OBJECTIVES: This study aimed to assess the economic burden of subsequent fracture in osteoporosis patients with incident fracture. METHODS: The authors conducted a retrospective cohort analysis of the South Korean national health insurance claims data. Study subjects included osteoporosis patients aged ≥50 with incident fracture (July 1, 2014-June 30, 2015). Fracture-related 1-year healthcare cost was evaluated after incident fracture for patients with and without subsequent fracture, defined as a fracture occurring within 2 years from incident fracture at a different site or at the same site after 6-months washout period. Per-patient-per-month (PPPM) cost was calculated by dividing each patient's cumulative healthcare cost until subsequent fracture with time-to-subsequent-fracture. For the patients without subsequent fracture, PPPM cost equaled 1-year monthly cost. A generalized linear model (GLM) was used to estimate the ratio of increase in healthcare cost to assess the economic impact of subsequent fracture. RESULTS: A total of 73,717 osteoporosis patients with incident fracture were identified, consisting of 52.1% vertebral, 1.9% hip, and 46.0% non-vertebral-non-hip fractures. Subsequent fracture occurred in 17.9% of patients with average time-to-subsequent-fracture of 256 days. Patients with subsequent fracture had significantly higher 1-year healthcare cost after incident fracture than those without subsequent fracture ($4,307 vs $1,721) and the difference was greater in PPPM cost ($930 vs $141). GLM analysis showed that having subsequent fracture increased both 1-year healthcare cost and PPPM cost by 1.91-fold (95% CI = 1.87-1.95) and 6.14-fold (95% CI = 5.99-6.28), respectively. CONCLUSIONS: Subsequent fracture imposes a substantial burden on osteoporosis patients and, therefore, more efforts are needed for preventing subsequent fracture among osteoporosis patients.

Incidence and risk factors of subsequent osteoporotic fracture: a nationwide cohort study in South Korea.

This study analyzed the incidence and risk factors of subsequent osteoporotic fractures in South Korea. The results showed that the incidence rate of subsequent fractures within 24 months was 10.23 per 100 person-years. Additionally, the index hip fracture site was a significant risk factor for a subsequent fracture. PURPOSE: To identify and analyze the incidence and risk factors of subsequent osteoporotic fractures in South Korea. METHODS: This retrospective cohort study analyzed data from the National Health Insurance Review and Assessment claims database from 2012 to 2017. Men and women with osteoporosis, aged ≥50 years, with index fractures between July 1, 2014, and July 1, 2015, were included. The incidence rate of subsequent fractures was calculated by determining the number of second event within 2 years from the index fracture. To identify the risk factors for subsequent fractures, we applied the Cox proportional hazard model to estimate the hazard ratios (HRs). RESULTS: Of the 73,717 patients with osteoporotic fractures, 13,203 (17.91%) had a subsequent fracture. The incidence rate of subsequent fractures within 24 months was 10.23/100 person-years. The index fracture site was a significant risk factor for a subsequent fracture, with the hip showing the highest risk (HR, 7.51; 95% confidence interval [CI], 6.77-8.34), followed by the vertebra (HR, 1.99; 95% CI, 1.91-2.06). The risk of subsequent fractures increased with a higher Charlson Comorbidity Index (CCI) score (CCI score ≥ 5: HR, 1.79; 95% CI, 1.67-1.92). CONCLUSION: The incidence rate of subsequent osteoporotic fractures in South Korea is similar or higher than that reported in the USA and Europe. A hip fracture within the prior 2 years, relative to other fracture sites, significantly increased the risk of subsequent fractures in osteoporosis patients. Patients who have these risk factors need closer disease management to prevent subsequent fractures.

Real-world treatment persistence of non-tumor necrosis factor inhibitors versus tumor necrosis factor inhibitors among patients with rheumatoid arthritis in South Korea.

Aims: We aimed to assess treatment persistence of tumor necrosis factor (TNF) inhibitors and non-TNF inhibitors in two groups of rheumatoid arthritis (RA) patients: biologic disease-modifying antirheumatic drug (bDMARD) initiators and switchers.Patients and methods: This retrospective cohort study utilized a national health insurance claims database. Patients aged ≥18 years initiating/switching bDMARD between 1 December 2013 and 31 December 2014, the index period, were followed for 12 months. Initiators who began treatment with a bDMARD during the index period were defined as having no bDMARD prescriptions for the previous year. Switchers who changed treatment from the previous bDMARD to the index bDMARD were defined as having different bDMARDs during the index period. Treatment persistence rates during the follow-up period were measured, and factors associated with non-persistence were assessed with the Cox proportional hazard model.Results: Of 2684 patients, treatment persistence rates were the highest for abatacept in initiators (69.3%) and tocilizumab in switchers (77.0%), while adalimumab showed the lowest persistence rates for both initiators and switchers (48.2%, 28.8%), followed by etanercept (51.3%, 41.0%). Adalimumab and etanercept were significantly more likely to show non-persistence (HR 1.58, 95% CI 1.27-1.96; HR 1.42, 95% CI 1.14-1.76) compared to infliximab for initiators, while tocilizumab was significantly more likely to show persistence (HR 0.411, 95% CI 0.206-0.819) in switchers.Conclusions: Non-TNF inhibitors showed higher persistence rates than TNF inhibitors in South Korean RA patients, and tocilizumab especially was associated with higher persistence in patients with inadequate response to TNF inhibitors. Good persistence with non-TNF inhibitors indicates the potential for long-term efficacy as first-line treatment.

Comparison of Effectiveness Between Delamanid and Bedaquiline Among Patients with Multidrug-Resistant Tuberculosis: A Markov Model Simulation Study.

BACKGROUND: No clear evidence on the comparative effectiveness of delamanid (DLM) and bedaquiline (BDQ) has been published. OBJECTIVE: This study aims to estimate the incremental effectiveness of DLM versus BDQ in patients with multidrug-resistant tuberculosis (MDR-TB). METHODS: We developed a Markov model based on a cohort with MDR-TB, which consisted of success, failure, loss to follow-up, and death. The cohort simulation was conducted assuming each patient was 36 years old and, lived until age 82, and that the cycle length was 1 year. Patients with an inadequate response to DLM, the background regimen, or BDQ for 2 years were transitioned through the next treatment sequence. We evaluated the incremental effectiveness of the drugs using the quality-adjusted life-year (QALY) resulting from this Markov model over a lifetime. RESULTS: The incremental effectiveness of DLM (13.96 QALYs) was greater by 2.44 QALYs per patient than the background regimen (11.52 QALY), while the incremental effectiveness of BDQ (10.40 QALY) was higher by 1.14 QALY per patient than the background regimen (9.26 QALY). Consequently, the incremental effectiveness of DLM was relatively more positive by 1.30 QALY than those of BDQ per patient over a lifetime. LIMITATIONS: This study is a simulation study. Therefore, the treatment sequence for patients may be different in the real world. CONCLUSIONS: Our lifetime simulated data found that DLM was relatively more favorable than BDQ. A Markov model can be considered an alternative approach when there is an absence of head-to-head clinical data.