Cost-effectiveness of Tofacitinib in the Treatment of Moderate to Severe Rheumatoid Arthritis in South Korea.

PURPOSE: This study evaluated the cost-effectiveness of introducing tofacitinib, an oral Janus kinase inhibitor, to the treatment of Korean patients with rheumatoid arthritis (RA) and an inadequate response to conventional disease-modifying antirheumatic drugs. METHODS: In this cost-utility analysis model, patients transitioned through treatment sequences based on Korean guidelines for RA patients with inadequate response to conventional disease-modifying antirheumatic drugs. Lifetime health-related quality of life and costs were evaluated. Characteristics of the model cohort were based on those reported by the Oral Rheumatoid Arthritis phase 3 triaL (ORAL) Standard randomized Controlled trial of tofacitinib or adalimumab versus placebo. Efficacy was assessed using American College of Rheumatology response rates, converted to the changes in Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, based on tofacitinib clinical trials data. Published clinical trial data on discontinuation rates of the indicated drugs were incorporated in the model. The HAQ-DI scores were mapped onto utility values to calculate outcomes in terms of quality-adjusted life-years (QALYs); HAQ-DI-to-utility (EuroQoL 5D) mapping was based on data from 5 tofacitinib clinical trials. Costs were analyzed from a societal perspective, with values expressed in 2013 Korean won (KRW). Cost-effectiveness is presented in terms of incremental cost-effectiveness ratios (ICERs). One-way sensitivity analyses were performed to assess the robustness of the model. FINDINGS: First-line tofacitinib used before the standard of care (base-case analysis) increased both treatment costs and QALYs gained versus the standard-of-care treatment sequence, resulting in an ICER of KRW 13,228,910 per QALY. Tofacitinib also increased costs and QALYs gained when incorporated as a second-, third-, or fourth-line therapy. The inclusion of first-line tofacitinib increased the duration of active immunomodulatory therapy from 9.4 to 13.2 years. Tofacitinib-associated increases in costs were attributable to the increased lifetime drug costs. In sensitivity analyses, variations in input parameters and assumptions yielded ICERs in the range of KRW 6,995,719 per QALY to KRW 37,450,109 per QALY. IMPLICATIONS: From a societal perspective, the inclusion of tofacitinib as a treatment strategy for moderate to severe RA is cost-effective; this conclusion was considered robust based on multiple sensitivity analyses. The study was limited by the lack of clinical data on follow-up therapy after tofacitinib administration and a lack of long-term data on discontinuation of drug use.

Cost-effectiveness analysis of low density lipoprotein cholesterol-lowering therapy in hypertensive patients with type 2 diabetes in Korea: single-pill regimen (amlodipine/atorvastatin) versus double-pill regimen (amlodipine+atorvastatin).

OBJECTIVES: Single-pill combination therapy (amlodipine/atorvastatin) might be more effective than double-pill therapy (amlodipine+atorvastatin) in patients with diabetes and concomitant hypertension requiring statin therapy. We compared the cost-effectiveness of a single-pill with that of double-pill for control of low density lipoprotein cholesterol (LDL-C) levels, with the ultimate goal of cardiovascular disease prevention, in these patients using a cost-effectiveness analysis model that considered medication adherence. METHODS: Effectiveness was defined as the percentage (%) attainment of target LDL-C levels (<100 mg/dL) based on adherence for each therapy. Adherence was defined as compliance to medication (≥80% proportion of days covered). A systematic review of the literature was conducted to determine the proportion of patients who were adherent and target goal attainment based on adherence level. The annual medication costs were based on the adherence levels for each regimen. The average cost-effectiveness ratio (ACER) was calculated as the cost per % attainment of the target LDL-C level. RESULTS: The ACER for the single-pill regimen was lower than for the double-pill regimen (4,123 vs. 6,062 Korean won per 1% achievement of target goal). Compared with the double-pill, the medication costs were approximately 32% lower with the single-pill. CONCLUSION: A single-pill for reductions in LDL-C is cost-effective compared with double-pill in hypertensive patients with type 2 diabetes.

Amlodipine and cardiovascular outcomes in hypertensive patients: meta-analysis comparing amlodipine-based versus other antihypertensive therapy.

BACKGROUND/AIMS: This meta-analysis compared the effects of amlodipine besylate, a charged dihydropyridine-type calcium channel blocker (CCB), with other non-CCB antihypertensive therapies regarding the cardiovascular outcome. METHODS: Data from seven long-term outcome trials comparing the cardiovascular outcomes of an amlodipine-based regimen with other active regimens were pooled and analyzed. RESULTS: The risk of myocardial infarction was significantly decreased with an amlodipine-based regimen compared with a non-CCB-based regimen (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.84 to 0.99; p = 0.03). The risk of stroke was also significantly decreased (OR, 0.84; 95% CI, 0.79 to 0.90; p < 0.00001). The risk of heart failure increased slightly with marginal significance for an amlodipine-based regimen compared with a non-CCB-based regimen (OR, 1.14; 95% CI, 0.98 to 1.31; p = 0.08). However, when compared overall with ß-blockers and diuretics, amlodipine showed a comparable risk. Amlodipine-based regimens demonstrated a 10% risk reduction in overall cardiovascular events (OR, 0.90; 95% CI, 0.82 to 0.99; p = 0.02) and total mortality (OR, 0.95; 95% CI, 0.91 to 0.99; p = 0.01). CONCLUSIONS: Amlodipine reduced the risk of total cardiovascular events as well as all-cause mortality compared with non-CCB-based regimens, indicating its benefit for high-risk cardiac patients.

Pre-emptive and multi-modal perioperative pain management may improve quality of life in patients undergoing spinal surgery.

BACKGROUND: Compared to an abundance of data on surgical techniques for degenerative spine conditions and the outcomes thereof, little is available to guide optimal perioperative pain management after spinal surgery. The aim of this study was to survey patterns of perioperative pain management after spinal surgery and to investigate the effects of perioperative pain management, such as pre-emptive analgesia and multi-modal postoperative pain management, on acute postoperative satisfaction, pain reduction, and health-related quality of life in patients undergoing spinal surgery. STUDY DESIGN: Non-blind multicenter prospective observational clinical series. SETTING: Seventeen tertiary hospitals (14 hospitals attached to medical colleges and 3 general hospitals). METHODS: Pain management protocols of 393 patients (153 men, 240 women; mean age of 67 years, ranging from 21 to 91 years) from 17 tertiary hospitals after spinal surgery for degenerative spine disease were evaluated using a self-administered questionnaire. RESULTS: A total of 79 (20%) patients received pre-emptive analgesics, which included cyclooxygenase-2 (COX-2) inhibitors, with or without administration of anticonvulsants, immediately before surgery at the time of antibiotic prophylaxis. Postoperative pain was managed mainly by multi-modal therapy (363 cases, 92%), along with various combinations of patient controlled anesthesia (PCA), conventional nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, and narcotics. Self-reported levels of pain were not significantly different among postoperative multiple modalities of pain management, but were different significantly for pre-emptive pain management regimens (P < 0.05, independent t-test). The number of patients that reported the self-administrative use of PCA was higher in the no pre-emptive pain management group compared to the pre-emptive group (P < 0.05). In regards to EQ-5D usual activity, depression/anxiety and self-care improved significantly in the pre-emptive pain management group when measured at 2 weeks postoperative (P < 0.05). LIMITATIONS: The limitation of our study is that it is not a randomized controlled observational study. CONCLUSIONS: Pre-emptive analgesia and multi-modal pain management after spinal surgery may lead to better health-related quality of life, greater patient satisfaction, and less postoperative pain.

Evaluation of the willingness-to-pay for cancer treatment in Korean metastatic breast cancer patients: a multicenter, cross-sectional study.

AIMS: To evaluate the inherent value of breast cancer therapy a willingness-to-pay (WTP) study was conducted in Korean patients with metastatic breast cancer. METHODS: Patients were prospectively enrolled from four study centers and completed quality of life questionnaires to reflect their status pre-cancer and their current health status. Clinical and socioeconomic data were collected to characterize the population and utilize during modeling. Patients' WTP for breast cancer treatment was assessed using an open-ended question following three rounds of bidding to better hone in on their maximal WTP, starting with one of three randomly assigned start bids. Predictors of patient WTP was evaluated using linear regression models. Associations between WTP and other parameters were evaluated with correlations. RESULTS: Korean metastatic breast cancer patients were WTP an average of KRW 8 696 329 (US$7555) per month to return to their pre-cancer health state, with those who were recently diagnosed as WTP the most (KRW 12 955 000 [$11 254]). WTP was closely associated with the patient's education level, income, personal financial difficulties, Eastern Cooperative Oncology Group performance status, and their experience of arm symptoms. CONCLUSION: The results suggest that patients are WTP significant amounts per month for treatment. Breast cancer patients are heavily burdened physically, mentally and financially, and the present study indicated this significant financial burden by disclosing its relationship with WTP. Providing a better understanding of the inherent value of treatment will allow Koreans to better evaluate treatment in the coming era of personalized medicine.

Mapping the cancer-specific EORTC QLQ-C30 and EORTC QLQ-BR23 to the generic EQ-5D in metastatic breast cancer patients.

PURPOSE: To develop a mapping algorithm for a conversion of the EORTC QLQ-C30 and EORTC QLQ BR-23 into the EQ-5D-derived utilities in metastatic breast cancer (MBC) patients. METHODS: We enrolled 199 patients with MBC from four leading Korean hospitals in 2009. EQ-5D utility, cancer-specific (QLQ-C30) and breast cancer-specific quality of life data (QLQ-BR23) and selected clinical and demographic information were collected from the study participants. Ordinary least squares regression models were used to model the EQ-5D using QLQ-C30 and QLQ-BR23 scale scores. To select the best model specification, six different sets of explanatory variables were compared. RESULT: Regression analysis with the multiitem scale scores of QLQ-C30 was the best-performing model, explaining for 48.7% of the observed EQ-5D variation. Its mean absolute error between the observed and predicted EQ-5D utilities (0.092) and relative prediction error (2.784%) was among the smallest. Also, this mapping model showed the least systematic errors according to disease severity. CONCLUSIONS: The mapping algorithms developed have good predictive validity, and therefore, they enable researchers to translate cancer-specific health-related quality of life measures to the preference-adjusted health status of MBC patients.

The financial burden of asthma: a nationwide comprehensive survey conducted in the republic of Korea.

PURPOSE: Asthma-related morbidity and mortality are increasing, and the financial burden imposed by this condition will substantially increase. Nevertheless, little information is available regarding the nature and magnitude of the burden due to asthma at the national level. This study was conducted to characterize the financial burden imposed by asthma in the Republic of Korea at the national level. METHODS: The overall prevalence of asthma and the costs of related medical services were determined using data from the National Health Insurance Corporation, which is responsible for the National Health Insurance scheme. Indirect costs, including expenditures on complementary and alternative medicines, and the economic impact of an impaired quality of life (intangible costs) were estimated by surveying 660 asthmatics, and these estimates were transformed to the national level using the prevalence of asthma. RESULTS: The prevalence of asthma and total costs related to the disease in 2004 were 4.19% and $2.04 billion, respectively. Direct costs and indirect costs contributed equally to total costs (46.9% and 53.1%, respectively). However, when intangible costs were included, total costs rose to $4.11 billion, which was equivalent to 0.44% of the national gross domestic product in 2004. CONCLUSIONS: The results provide evidence that asthma is a major health cost factor in the Republic of Korea and that intangible costs associated with asthma are significant cost drivers.

Results of a Markov model analysis to assess the cost-effectiveness of a single tablet of fixed-dose amlodipine and atorvastatin for the primary prevention of cardiovascular disease in Korea.

BACKGROUND: In Korea, the treatment of hypertension and dyslipidemia constitutes an important strategy for the prevention of cardiovascular disease (CVD). OBJECTIVE: This study sought to investigate the cost-effectiveness (from the Korean health care system perspective) of prescribing a proprietary formulation single-tablet fixed-dose combination of amlodipine and atorvastatin (at weighted mean doses of 5 mg and 10.25 mg, respectively) to all eligible patients aged > or = 45 years for the primary prevention of CVD (ie, coronary heart disease and ischemic stroke) in Korea, compared with currently observed patterns of blood-pressure and lipid-lowering medication prescription and use. METHODS: A Markov model was developed with 4 health states: alive without CVD, alive with CVD, dead from CVD, and dead from non-CVD causes. The model population comprised 244 Koreans aged >/=45 years from the 2005 Korean National Health and Nutrition Examination Survey (KNHNES) without a history of myocardial infarction (MI) or stroke who met current criteria for both blood-pressure and lipid-lowering treatment. From a 2008 baseline, follow-up was simulated for 40 years. Cardiovascular risk was estimated for each subject individually using a multivariate, Asian population-specific equation, and updated with ongoing cycles. Decision analysis compared the effects of prescribing the fixed-dose combination to all subjects versus currently observed patterns of treatment. Data regarding the blood-pressure and lipid-lowering efficacies of combination therapy were drawn from the Respond trial. Costs of the fixed-dose combination tablet and CVD were sourced from pharmaceutical pricing lists and Korean Health Insurance Review and Assessment Services estimates, respectively. Utility values for CVD were obtained from a large Korean utility study. RESULTS: In the model, of the 244 treatment-eligible subjects, 126 (51.6%) and 13 (5.3%) were taking blood-pressure and lipid-lowering therapy, respectively. Use of single-tablet fixed-dose combination amlodipine and atorvastatin by all subjects was associated with estimated incremental cost-effectiveness ratios of 7,773,063 Korean won (KRW) per quality-adjusted life-year gained and 10,378,230 KRW per overall life-year gained (1300 KRW approximately US $1). Sensitivity and uncertainty analyses indicated these results to be robust. CONCLUSIONS: In this model, based on data from the 2005 KNHNES, hypertension and dyslipidemia were undertreated among Koreans aged > or = 45 years without a history of MI or stroke. The administration of single-tablet fixed-dose combination amlodipine and atorvastatin to all such individuals was likely to represent a cost-effective means of preventing first-onset CVD (ie, coronary heart disease and ischemic stroke) in this subgroup, compared with current patterns of treatment.

Results of a Markov model analysis to assess the cost-effectiveness of statin therapy for the primary prevention of cardiovascular disease in Korea: the Korean Individual-Microsimulation Model for Cardiovascular Health Interventions.

BACKGROUND: Although hyperlipidemia is well recognized as a risk factor for cardiovascular disease (CVD), there has been no appraisal of the economic impact of statin therapy in Korea. OBJECTIVE: The aim of this model analysis was to determine the cost-effectiveness of statin therapy versus no treatment for the primary prevention of CVD over a lifetime in Korea, from a health care system perspective. METHODS: We developed the Korean Individual-Microsimulation Model for Cardiovascular Health Interventions (KIMCHI), an epidemiologic and economic Markov model of first-onset CVD in Korea in which all individuals began the simulation in the health state alive without CVD, and moved among the 4 health states (alive without CVD, alive with CVD, dead from CVD, and dead from non-CVD causes) in yearly cycles for any specified time horizon, up to 40 years. KIMCHI was populated with 372 subjects from the 2005 Korean National Health and Nutrition Examination Survey (KNHNES) who were aged > or =45 years, did not have a history of myocardial infarction or ischemic stroke, and met current Korean reimbursement criteria for treatment with lipid-lowering medications. The probability of first-onset CVD was estimated for each study participant individually, based on an Asian population-specific risk equation that relied on an individual's sex, age, serum total cholesterol, systolic blood pressure, current smoking status, diabetes mellitus status, and body mass index. Statin treatment was represented by a hybrid of atorvastatin and simvastatin (the most popular statins in Korea), the lipid-modifying effects of which were de rived from a published meta-analysis. Data regarding utilities and costs of CVD (both those covered and not covered by insurance) were derived from published local sources. RESULTS: In the base case, the estimated incremental costutility ratio was 15,134,284 Korean won (KRW) per quality-adjusted life-year (QALY) gained, and the estimated incremental cost-effectiveness ratio was 20,657,829 KRW per life-year gained (LYG) (1200 KRW approximately US $1). Based on a willingness-to-pay (WTP) threshold of 30 million KRW per QALY saved, there was a 93.7% probability that statin therapy would be cost-effective. Given a WTP threshold of 20 million KRW per QALY, there was a 53.8% probability of being cost-effective. The probabilities at WTP thresholds of 30 and 20 million KRW per LYG were 62.4% and 25.8%, respectively. CONCLUSIONS: Based on this analysis using data from the 2005 KNHNES and the KIMCHI model, statin therapy is likely to be cost-effective for the primary prevention of CVD among Koreans aged > or =45 years. The probability of being cost-effective was greater at a threshold of 30 million KRW per QALY (93.7%) than at 20 million KRW per QALY (53.8%).

A catalogue of EQ-5D utility weights for chronic diseases among noninstitutionalized community residents in Korea.

OBJECTIVE: The main purpose of this study is to provide a national catalog of preference-based utility weights associated with major chronic diseases in Korea. METHODS: The 2005 Korea National Health and Nutrition Examination Survey was used to get EQ-5D scores for 27 major chronic diseases. The independent detrimental effect of each chronic disease was estimated using a censored least absolute deviations regression. RESULTS: The respondents (60.5%) rated their health as perfect or 11111 on the EQ-5D scale showing ceiling effect. Stroke (0.5067 approximately 0.5756) was the condition of the lowest EQ-5D utility weight and was followed by renal failure (0.6637 approximately 0.7739), angina pectoris (0.7325 approximately 0.8364), and arthritis (0.7621 approximately 0.8644). The marginal impact of each chronic disease after adjusting for age, sex, education, income, marital status, and the number of comorbid conditions was largest in stroke, arthritis, cancer, renal failure, and herniated disc. CONCLUSION: This study provided a nationally representative catalog of utility weights for major chronic diseases in Korea. The three most burdensome chronic diseases among Korean adults based on the regression analysis were stroke, arthritis, and cancer.

[Economic evaluation of gemcitabine-cisplatin chemotherapy for non small-cell lung cancer patient in an outpatient setting].

PURPOSE: This analysis was conducted to evaluate the cost-effectiveness of gemcitabine-cisplatin chemotherapy for non small-cell lung cancer patients in an outpatient setting compared with the traditional inpatient setting. METHODS: A cost-effective analysis was conducted from a societal perspective. The effects of treatment, which was measured as an adverse event rate, were abstracted from a published literature search and empirical data from one university hospital. The costs included both direct and indirect costs. Direct costs included hospitalizations, outpatient visits, and lab tests. Pharmaceutical costs were excluded in analysis because they were same for both options. Indirect costs included productivity loss of patients as well as care-givers. In order to determine the robustness of the results, sensitivity analysis on treatment protocol was conducted. RESULTS: Literature search showed no difference in adverse effect rates between inpatient treatment protocol and outpatient treatment protocol. Therefore, this analysis is a cost-minimization analysis. Cost-savings in the outpatient setting was 555,936 won for one treatment cycle. Our sensitivity analysis indicated that the outpatient chemotherapy still showed cost-savings, regardless of changes in treatment protocol. CONCLUSION: The outpatient gemcitabine-cisplatin chemotherapy for non small-cell lung cancer resulted in cost savings compared to inpatient chemotherapy. More importantly, outpatient chemotherapy could improve the utilization of health service resources in terms of available beds.

Are league tables controlling epidemic of caesarean sections in South Korea?

OBJECTIVE: To assess the impact of the publication of hospital caesarean section rates on the reduction of these rates in South Korea, and explore associated factors contributing to the decrease. DESIGN: Observational study. SETTING: South Korea. SAMPLE: Two hundred and sixty-three hospitals in South Korea. METHODS: The caesarean section rates of 263 hospitals, before and after the release of caesarean section rates to the public, were obtained. The factors influencing the reduction in hospital caesarean section rates were also explored using multiple logistic regression. MAIN OUTCOME MEASURE: Hospital caesarean section rates. RESULTS: After the release of information in 2000, the total (clinic and hospital) caesarean section rates in 2000 and 2001 decreased to 38.6% and 39.6%, respectively, from 43.0% in 1999. Caesarean section rates for hospitals were 45.9%, 42.7% and 44.6% in 1999, 2000 and 2001, respectively. Hospitals with the highest baseline caesarean section rates (OR 9.4, 95% CI 4.2-21.0) and highest number of deliveries (OR 8.1, 95% CI 2.1-31.1) were significant factors contributing independently to a decrease in caesarean section rates. Market share, competition, characteristics of revenue generation and ownership did not significantly influence the change of rates. CONCLUSION: The public release of information on caesarean section rates in Korea has reversed the ever-increasing trend in these rates. Hospitals with pre-existing high caesarean section rates or a larger number of deliveries were influenced by the information release and could be the main targets for interventions to decrease these rates.