Cost-consequence analysis of continuous denosumab therapy for osteoporosis treatment in South Korea.

BACKGROUND: Insurance reimbursement provisions in South Korea limit osteoporosis medication availability for patients with T-scores exceeding - 2.5. This study aimed to evaluate the financial impact and fracture prevention of continuous denosumab therapy until a T-score>-2.0 (Dmab-C strategy), versus discontinuation of denosumab after reaching T-score>-2.5 (Dmab-D strategy) in osteoporosis patients. METHODS: A cost-consequence analysis from a Korean healthcare system perspective was performed using a newly developed Markov model. The incidence of vertebral and non-vertebral fracture, fracture-related deaths, drug costs, and fracture-treatment costs were estimated and compared between Dmab-C and Dmab-D strategy over a lifetime in eligible patients aged 55 years. RESULTS: Base-case analysis revealed that Dmab-C prevented 32.21 vertebral fracture (VF) and 12.43 non-VF events per 100 patients over a lifetime, while reducing 1.29 fracture-related deaths. Lifetime direct healthcare cost saving per patient was KRW 1,354,655 if Dmab-C replaces Dmab-D. When productivity losses were considered, Dmab-C saved KRW 29,025,949 per patient compared to Dmab-D. The additional treatment costs of Dmab-C could be offset by the higher subsequent treatment costs and fracture treatment costs of Dmab-D. The sensitivity analysis showed consistent patterns with results of the base-case analysis. CONCLUSION: Continuous treatment using denosumab until osteoporosis patients achieve and maintain a T-score of -2.0 would provide greater clinical and economic benefits in terms of fracture prevention and reduced mortality risks compared to outcomes from discontinuing treatment at a T-score of -2.5 or above. This new treatment strategy would effectively lower the risk of fractures and fracture-related mortality, ultimately leading to lower medical expenses.

Aging and direct medical costs of osteoporotic fractures.

INTRODUCTION: This study estimated the direct medical costs of osteoporotic fractures from a large claims database in Korea. MATERIALS AND METHODS: We compared the medical costs of hip, vertebral, and wrist fractures between two age groups (50-64 years vs 65 years and older). We used a generalized linear model to investigate the drivers of osteoporotic fracture medical costs. RESULTS: Hip fractures had the highest costs, regardless of age, followed by vertebral and wrist. The cost of hip fracture was USD 7285 for those aged 65 years and over and USD 6589 for those aged 50-64 years. The length of hospital days was higher in hip fracture patients, regardless of age, followed by vertebral and wrist. As the number of hospitalizations increased, the medical cost increased by 33.0% (p < 0.0001). Patients older than 65 years who were hospitalized for a fracture had a longer total length of hospital stay, compared to patients aged 50-64, regardlessness of the site of the fracture. The cost of treating fractures among those 65 years and older increased by 31.8% compared to those 50-64 years old (p < 0.0001). The direct medical costs increased by 8.6% as the number of fractures increased (p = 0.041). CONCLUSIONS: We identified that osteoporotic fracture-related medical costs and hospitalization days increased with age. Interventions are effective in reducing fracture risk the potential to yield substantial cost savings.

Zoledronic acid and skeletal-related events in patients with bone metastatic cancer or multiple myeloma.

INTRODUCTION: Investigations of ZA effectiveness using large, real-world databases are rare. We examined whether zoledronic acid (ZA) decreased the risk of skeletal-related events (SREs) among patients with bone metastases (BMs) from breast cancer (BC) or prostate cancer (PC), or multiple myeloma (MM) in routine clinical practice. MATERIALS AND METHODS: We conducted a propensity score-matched cohort study using the Korean National Health Insurance database. Our cohort included patients diagnosed with BM after BC or PC, or MM between 2004 and 2015. SRE was defined as having a record of pathologic fracture, spinal cord compression, radiation, or surgery to bone. The incidence of multiple SREs was calculated according to SRE history. We calculated the incidence rate ratio (IRR) to examine the relative difference in the risk of SREs of ZA users compared to those of ZA non-user. RESULTS: Among 111,679 patients, diagnosed with BM and one of the three cancer types, 5608 were included in the analysis after propensity score matching. A decreased risk of SREs was observed for the ZA use in patients with history of SRE in BC [IRR = 0.74, 95% confidence interval (CI) = 0.66-0.83], PC (IRR = 0.86, 95% CI = 0.73-1.02), and MM (IRR = 0.74, 95% CI = 0.59-0.93). For patients without SRE history, ZA use was not associated with decreased risks of SREs, but rather increased the risks (BC: IRR = 1.96, 95% CI 1.87-2.05; PC: IRR = 1.66, 95% CI 1.54-1.80; MM: IRR = 1.92, 95% CI 1.57-2.34). CONCLUSIONS: Our study suggests that the ZA use was associated with a decreased risk of SRE for patients with SRE history. However, no preventive effects of ZA were observed for patients without history.

Cost-Effectiveness of Denosumab for the Treatment of Postmenopausal Osteoporosis in South Korea.

BACKGROUND: Osteoporosis is a progressive skeletal disease associated with an increased risk of bone fracture. This study aimed to estimate the cost-effectiveness of denosumab for osteoporotic fracture prevention compared to bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate) and selective estrogen receptor modulators (raloxifene) in a cohort of postmenopausal women with osteoporosis. METHODS: A Markov model was used to evaluate the cost and effectiveness of denosumab versus comparators. The model had a cycle length of 6 months and was run from the age of 68 years to individual patients' lifetime or the age of 100 years. The health states considered in the model were well, hip fracture, vertebral fracture, wrist fracture, other osteoporotic fracture, post-hip fracture, post-vertebral fracture, and death. Recent local data were used as inputs for the model parameters. A discount rate of 4.5% was applied to both costs and outcomes. RESULTS: From the perspective of the healthcare system, denosumab was cost-effective or cost-saving compared to all comparators, considering one unit of Korea's gross domestic product per capita, USA dollar (USD) 34,870. Denosumab was cost-saving compared to ibandronate (oral) and raloxifene. Compared to alendronate, denosumab was cost-effective with an incremental cost-effectiveness ratio (ICER) of USD 767.10 per quality-adjusted life year (QALY). The ICER of denosumab vs. ibandronate IV, risedronate, and zoledronate was USD 685.63, USD 1,469.71, USD 4,668.53 per QALY, respectively. CONCLUSIONS: The findings of this analysis suggest that denosumab is a cost-effective therapeutic option for preventing fractures in postmenopausal women with osteoporosis in South Korea.

Health state utility values of osteoporotic fractures among Korean women.

Objectives: This study aimed to investigate health state utility values in eight health states related to osteoporosis and osteoporotic fractures using time trade-off (TTO) technique among postmenopausal Korean women.Methods: Scenarios describing eight health states including osteoporosis and hip, vertebral, post-hip, post-vertebral, ankle, humerus, and wrist fractures were developed and presented to 500 female participants aged 45 to 59 years who were selected with probability proportionate to age group and region for this investigation. Each health states valuation was derived using the trade-off (TTO) technique. Ten years of a given health state was traded off with a shorter length of time in full health.Results: Mean scores of each state were calculated. Osteoporosis scored the highest (0.669 ± 0.155), followed by wrist fracture (0.656 ± 0.151). Hip (0.298 ± 0.158) and vertebral (0.298 ± 0.160) fractures were found to be the worst health states. Post-hip (0.446 ± 0.159) and post-vertebral fractures (0.455 ± 0.160) were also considered undesirable states. All fractures were associated with disutilities, ranging from a mean of -0.013 to -0.371. These values were statistically significant (p < 0.0001). Hip and vertebral fractures are among the most serious consequences of osteoporotic fractures.Conclusions: The vertebral and hip fractures marked the lowest utility scores among post-menopausal women in Korea.

Burden of Osteoporotic Fractures Using Disability-Adjusted Life Years in South Korea.

There is an increase in the number of patients with osteoporotic fractures due to the aging population in Korea. This study investigated the burden of osteoporotic fractures including hip, spine, and wrist fractures in the Korean population by estimating disability-adjusted life years (DALYs). The DALY for a given condition in a population captures years of life lost due to premature death and years of life lived with a disability and its severity and duration. To calculate DALYs from all relevant data collected for the 3 conditions, we used a DALY calculation template provided by the World Health Organization in 2014. DALYs per 100 000 for vertebral fractures (3168) were higher than those of hip fractures (2496) in women. Wrist fractures (1038) had the least burden, and the difference between men and women was the lowest. The aging population is expected to increase the burden of osteoporosis.

Disability Weights for Osteoporosis and Osteoporotic Fractures in South Korea.

BACKGROUND: Korea is expected to become an ultra-aged society, in which the elderly population will account for more than 20% of the total population, after 2025. Thus, the social costs due to osteoporotic fractures are expected to increase. Therefore, this study aimed to measure disability weights (DWs) of osteoporosis and osteoporotic fractures in Korea. METHODS: The scenarios were developed to standardize the severity of 6 health statuses: osteoporosis and osteoporotic fractures including wrist, hip, post-hip, vertebral, and post-vertebral fracture. The values for these 6 health statuses were sought via a person trade-off (PTO) approach. We measured the value by PTO and we calculated it to DW of 6 health statuses. Three clinical expertise panels of 33 experts were established, and face-to-face interviews were conducted from July to December 2017. RESULTS: The distribution of DW varied by panel. DWs ranged from 0.5 (Osteoporosis) to 0.857 (Hip fracture) for Panel 1, 0.091 (Osteoporosis) to 0.5 (Hip fracture) for Panel 2, and 0.091 (Osteoporosis) to 0.726 (Hip fracture) for Panel 3. The final values for the 6 health statuses obtained by pooling all data from 3 panels ranged from 0.286 (Osteoporosis) to 0.750 (Hip fracture). There was no significant difference in rankings for the 6 health statuses among the 3 panels. CONCLUSIONS: Comparing the DW of osteoporotic fracture in this study with other diseases in previous studies, it is predicted that osteoporotic fractures, especially hip fractures, will have a considerable burden of disease.

Incidence of skeletal-related events in patients with breast or prostate cancer-induced bone metastasis or multiple myeloma: A 12-year longitudinal nationwide healthcare database study.

BACKGROUND: This study examined the incidence of skeletal-related events (SRE) among patients with breast cancer (BC)- or prostate cancer (PC)-induced bone metastasis or multiple myeloma (MM) based on a population-based, 12-year healthcare database. METHODS: Patients aged ≥18 years with bone metastasis from BC or PC or with MM between 2004 and 2015 were included. SRE was defined as pathologic fracture, spinal cord compression, radiation, or surgery to bone. Patients were followed-up from the initial diagnosis of bone metastasis (for those with BC or PC) or MM until SRE occurrence. To estimate multiple SREs, we applied a 21-day time window to ensure that subsequent SREs occurred independently from the previous event. We calculated the incidence and 95% confidence intervals (CIs), stratified according to the previous SRE history. RESULTS: Our cohort included 53,231 patients, including 23,811 with BC, 19,170 with PC, and 10,250 with MM. The incidence of multiple SREs in the 21-day time window was 1.03 (95% CI = 1.01-1.05) in patients with previous SRE history and 0.19 (95% CI = 0.19-0.20) in those without. The cumulative SRE incidences were 47%, 31.4%, and 38.0% in BC, PC, and MM patients. CONCLUSION: The incidences of multiple SREs in BC- or PC-induced bone metastasis or MM in this 12-year South Korean cohort were slightly higher than those in European countries. Our study provided real-world evidence that patients with BC- or PC-induced bone metastasis or MM are at high risk of SRE.