Economic Evaluation of Anticyclic Citrullinated Peptide Positivity in Rheumatoid Arthritis.

BACKGROUND: Anticyclic citrullinated peptide (anti-CCP) positivity may be a strong predictor of joint erosion and a potential biomarker for guiding treatment decisions for rheumatoid arthritis (RA). However, limited studies are currently available on the effect of anti-CCP positivity on health care utilization and/or medical costs of RA patients. OBJECTIVE: To investigate short-term and long-term direct health care expenditures associated with anti-CCP positivity in newly diagnosed RA patients. METHODS: A retrospective cohort study was conducted in adult RA patients within a U.S. integrated health care delivery system (January 1, 2007-June 30, 2015). Patients were required to have 2 RA diagnoses and treatment with a conventional or biologic disease-modifying antirheumatic drug (DMARD) within 12 months. The first RA diagnosis date was labeled as the index date, and patients were followed until they left the health plan, died, or reached the end of the study period. Patient demographics, anti-CCP results, comorbid conditions, and health care resource utilization during baseline (12 months before the index date) and follow-up periods were collected. Nationally recognized direct medical costs were assigned to health care utilization to calculate health care costs in 2015 U.S. dollars. The baseline differences between anti-CCP positivity and negativity and differences in censoring during follow-up were addressed using propensity scores. The mean differences in costs were estimated using recycled prediction methods. RESULTS: 2,448 newly diagnosed RA patients were identified and followed for a median of 3.7 years (range = 1-8 years). At baseline, 65.8% of patients were anti-CCP positive. Anti-CCP-positive patients had fewer comorbid conditions at baseline. During the first 12 months of follow-up, median (interquartile range) total health care expenditures for anti-CCP-positive and anti-CCP-negative patients were $6,200 ($3,563-$13,260) and $7,022 ($3,885-$12,995), respectively. After adjusting for baseline differences, total incremental mean cost associated with anti-CCP positivity during the first 12 months was estimated to be $2,163 per patient (P = 0.001). The annual incremental costs in anti-CCP-positive patients became progressively larger over time, from $2,163 during the first year to $5,062 during the fourth year. Anti-CCP positivity was associated with higher prescription, laboratory testing, and rheumatologist utilization. A higher percentage of anti-CCP-positive patients received 1 or more biologic DMARDs (11.6% for anti-CCP-positive vs. 5.7% for anti-CCP negative; P < 0.001) compared with anti-CCP-negative patients during the 12-month follow-up, which resulted in $2,499 in incremental prescription costs (P < 0.001). Total additional burden associated with anti-CCP positivity during the first 4 years was estimated to be $14,089 per patient. CONCLUSIONS: In newly diagnosed RA patients, higher economic burden associated with anti-CCP positivity was mainly driven by prescription costs. DISCLOSURES: This research and manuscript were funded by Bristol-Myers Squibb (BMS). Alemao and Connolly are employees and shareholders of BMS and participated in the design of the study, interpretation of the data, review/revision of the manuscript, and approval of the final version of the manuscript. An and Cheetham received a grant from BMS for this research. At the time of this study, An was employed by Western University of Health Sciences, and Cheetham was employed by Kaiser Permanente Southern California. Bider-Canfield, Kang, and Lin have nothing to disclose. Some study results were presented as a poster at the American College of Rheumatology Annual Meeting; November 5, 2017; San Diego, CA, and at the International Society for Pharmacoeconomics and Outcomes Research Meeting; May 19, 2018; Baltimore, MD.

Timing of Abatacept Before Elective Arthroplasty and Risk of Postoperative Outcomes.

OBJECTIVE: Guidelines recommend withholding biologic therapies before hip and knee arthroplasty, yet evidence to inform optimal timing is limited. The aim of this study was to determine whether withholding abatacept infusions is associated with lower risk of adverse postoperative outcomes. METHODS: This retrospective cohort study, which used US Medicare and Truven MarketScan administrative data from January 2006 to September 2015, evaluated adults with rheumatoid arthritis who received intravenous abatacept (precisely dated in claims data) within 6 months of elective primary or revision hip or knee arthroplasty. Propensity weighted analyses using inverse probability weights compared the risk of 30-day hospitalized infection and 1-year prosthetic joint infection (PJI) between patients with different abatacept stop timing (time between last infusion and surgery). Secondary analyses evaluated nonurinary hospitalized infections and 30-day readmissions. RESULTS: After 1,939 surgeries among 1,780 patients, there were 175 hospitalized infections (9.0%), 115 nonurinary hospitalized infections (5.9%), 39 PJIs (2.4/100 person-years), and 114/1,815 30-day readmissions (6.3%). There were no significant differences in outcomes with abatacept stop timing <4 weeks (1 dosing interval) versus 4-8 weeks (hospitalized infection odds ratio [OR] 0.93 [95% confidence interval (95% CI) 0.65-1.34]; nonurinary hospitalized infection OR 0.93 [95% CI 0.60-1.44]; PJI hazard ratio 1.29 [95% CI 0.62-2.69]; 30-day readmission OR 1.00 [95% CI 0.65-1.54]). Similarly, there were no significant differences in outcomes with abatacept stop timing <4 weeks versus ≥8 weeks. Glucocorticoid use >7.5 mg/day was associated with greater risk of hospitalized infection (OR 2.19 [95% CI 1.28-3.77]) and nonurinary hospitalized infection (OR 2.38 [95% CI 1.22-4.64]). CONCLUSION: Compared to continuing intravenous abatacept, withholding abatacept for ≥4 weeks (one dosing interval) before surgery was not associated with a lower risk of hospitalized infection, nonurinary hospitalized infection, PJI, or 30-day readmission.

Conceptual model for the health technology assessment of current and novel interventions in rheumatoid arthritis.

The objective of this study was to evaluate current approaches to economic modeling in rheumatoid arthritis (RA) and propose a new conceptual model for evaluation of the cost-effectiveness of RA interventions. We followed recommendations from the International Society of Pharmacoeconomics and Outcomes Research-Society of Medical Decision Making (ISPOR-SMDM) Modeling Good Research Practices Task Force-2. The process involved scoping the decision problem by a working group and drafting a preliminary cost-effectiveness model framework. A systematic literature review (SLR) of existing decision-analytic models was performed and analysis of an RA registry was conducted to inform the structure of the draft conceptual model. Finally, an expert panel was convened to seek input on the draft conceptual model. The proposed conceptual model consists of three separate modules: 1) patient characteristic module, 2) treatment module, and 3) outcome module. Consistent with the scope, the conceptual model proposed six changes to current economic models in RA. These changes proposed are to: 1) use composite measures of disease activity to evaluate treatment response as well as disease progression (at least two measures should be considered, one as the base case and one as a sensitivity analysis); 2) conduct utility mapping based on disease activity measures; 3) incorporate subgroups based on guideline-recommended prognostic factors; 4) integrate realistic treatment patterns based on clinical practice/registry datasets; 5) assimilate outcomes that are not joint related (extra-articular outcomes); and 6) assess mortality based on disease activity. We proposed a conceptual model that incorporates the current understanding of clinical and real-world evidence in RA, as well as of existing modeling assumptions. The proposed model framework was reviewed with experts and could serve as a foundation for developing future cost-effectiveness models in RA.

Cost-Effectiveness Analysis of Abatacept Compared with Adalimumab on Background Methotrexate in Biologic-Naive Adult Patients with Rheumatoid Arthritis and Poor Prognosis.

OBJECTIVES: To assess cost effectiveness of abatacept versus adalimumab, each administered with methotrexate, in treating patients with rheumatoid arthritis (RA) stratified according to baseline anticitrullinated protein antibody (ACPA) levels (marker of poor prognosis in RA). METHODS: A payer-perspective cost-effectiveness model simulated disease progression in patients with RA who had previously failed conventional disease-modifying antirheumatic drugs and were starting biologic therapy. Patients commenced treatment with abatacept or adalimumab plus methotrexate and were evaluated after 6 months. Therapy continuation was based on the European League Against Rheumatism treatment response; disease progression was based on the Health Assessment Questionnaire Disability Index score. These score changes were used to estimate health state utilities and direct medical costs. Quality-adjusted life-years (QALYs) and incremental cost per QALY gained were calculated by baseline ACPA groups (Q1, 28-234 AU/ml; Q2, 235-609 AU/ml; Q3, 613-1045 AU/ml; and Q4, 1060-4894 AU/ml). Scenario analysis and one-way and probabilistic sensitivity analyses were used to evaluate robustness of model assumptions. RESULTS: Abatacept resulted in QALY gain versus adalimumab in ACPA Q1, Q3, and Q4; between-treatment difference (difference: Q1, -0.115 Q2, -0.009 Q3, 0.045; and Q4, 0.279). Total lifetime discounted cost was higher for abatacept versus adalimumab in most quartiles (Q2, £77,612 vs. £77,546; Q3, £74,441 vs. £73,263; and Q4, £78,428 vs. £76,696) because of longer time on treatment. Incremental cost per QALY for abatacept (vs. adalimumab) was the lowest in the high ACPA titer group (Q4, £6200/QALY), followed by the next lowest titer group (Q3, £26,272/QALY). CONCLUSIONS: Abatacept is a cost effective alternative to adalimumab in patients with RA with high ACPA levels.

Traditional Cardiovascular Disease Risk Factor Management in Rheumatoid Arthritis Compared to Matched Nonrheumatoid Arthritis in a US Managed Care Setting.

OBJECTIVE: To compare traditional cardiovascular (CV) risk factor management among patients with rheumatoid arthritis (RA) to that of matched non-RA controls within a large US managed care setting. METHODS: Adult patients with RA and age- and sex-matched general population (general controls) or osteoarthritis (OA) controls were identified between January 1, 2007 and December 31, 2011. We compared health care utilization, measurement, treatment, and treatment target achievement of traditional CV risk factors among subgroups of CV comorbidity during 1 year of followup between RA and controls. RESULTS: A total of 9,440 RA patients, 31,009 general controls, and 10,352 OA controls were included. The proportions with measurements (blood pressure [BP], low-density lipoprotein [LDL] cholesterol, or hemoglobin A1c ), treatment (antihypertensive, statin, or anti-diabetes mellitus medications), and treatment target achievement were slightly higher in patients with RA compared with general controls. Controlling for other factors, RA patients were more likely to have a measurement of BP (odds ratio [OR] 16.77 [95% confidence interval (95% CI) 10.01-28.08]) or LDL cholesterol (OR 1.25 [95% CI 1.13-1.39]), and to receive antihypertensive (OR 1.84 [95% CI 1.47-2.30]) or anti-diabetic medications (OR 1.26 [95% CI 1.01-1.56]) compared to general controls. RA was not associated with receiving a statin (OR 1.01 [95% CI 0.92-1.12]); however, a target LDL level was more likely to be achieved in RA compared to general controls (OR 1.27 [95% CI 1.17-1.37]) as well as target levels of BP and hemoglobin A1c . These results were consistent with results for OA controls except for a lower probability of receiving a statin in RA compared to OA. CONCLUSION: Traditional CV risk factors in patients with RA were not less aggressively managed compared to non-RA controls.

Determinants of medicare all-cause costs among elderly patients with renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is the third most common genitourinary cancer and the most common primary renal neoplasm. Estimates of the economic burden of RCC in the United States range from approximately $400 million (in year 2000 dollars) to $4.4 billion (in year 2005 dollars). Actual costs associated with RCC, particularly for elderly Medicare patients who account for 46% of U.S. patients hospitalized for RCC, are poorly understood. OBJECTIVE: To estimate all-cause health care costs associated with RCC using the combined Surveillance Epidemiology and End Results (SEER)-Medicare database. METHODS: The sample was limited to non-HMO patients aged 65 years or older who were diagnosed with a first primary RCC (SEER site recode 59, kidney and renal pelvis) between 1995 and 2002. Our final sample included 4,938 patients with RCC and 9,876 non-HMO noncancer comparison group cases without chronic renal disease drawn from the SEER 5% Medicare sample and matched by a propensity score calculated from age, gender, race/ethnicity, and comorbidities. Costs were defined as payments made by Medicare for all-cause medical treatments including inpatient stays, emergency room visits, outpatient procedures, office visits, home health visits, durable medical equipment, and hospice care, but excluding out-patient prescription drugs. Using the method of Bang and Tsiatis (2000), we estimated cumulative costs at 1 and 5 years by estimating average costs for each patient in each month up to 60 months following diagnosis. Total costs were weighted sums of monthly costs, where weights were the inverse probability that the patient was not censored, and inverse probabilities were estimated by Kaplan-Meier estimates of time to censoring. Using the method of Lin (2000), we performed multivariate analyses of costs by fitting each of the 60 monthly costs to linear models that controlled for demographic characteristics and comorbidities. Marginal effects of covariates on 1- and 5-year costs were obtained by summing the coefficients for months 1 through 12 and months 1 through 60, respectively. Confidence intervals were obtained by bootstrapping. RESULTS: Patients with RCC and matched comparison group cases had similar demographic characteristics, comorbidities, and chronic conditions. At the start of the fifth year post-diagnosis, there were 1,208 Medicare RCC cases of the original 4,938 (20.8%). Mean costs per patient per month (PPPM) in the first year were $3,673 for patients with RCC and $793 for comparison group patients. PPPM costs were higher for RCC patients with more advanced stage (i.e., regional or distant) disease. Average cumulative total costs for RCC patients were $33,605 per patient in the first year following diagnosis and $59,397 per patient in the first 5 years following diagnosis. Several patient-specific factors were associated with 1- and 5-year costs in multivariate analyses, including age, race/ethnicity, and comorbidities. Among RCC patients, treatment with surgery and radiation was associated with higher costs per patient than treatment with surgery alone at 1 year ($24,556, 95% CI = $16,673-$32,940) and 5 years ($30,540, 95% CI = $17,853-$43,648). RCC patients who received chemotherapy as part of their treatment regimen also had significantly higher costs per patient than those who received surgery alone at 1 year ($15,144, 95% CI = $ 9,979-$20,344) and 5 years ($13,440, 95% CI = $1,257-$27,572). CONCLUSIONS: Newly diagnosed RCC is associated with a significant economic burden, which is largely determined by several patient characteristics, disease stage, and treatment choice.

Inverse probability weighting to control for censoring in a post hoc analysis of quality-adjusted survival data from a clinical trial of temsirolimus for renal cell carcinoma.

OBJECTIVE: This post hoc analysis evaluated treatment-associated quality-adjusted survival (QAS) in patients randomly assigned to temsirolimus or interferon alfa (IFN-alfa), corrected for censoring using inverse probability weighting (IPW), in the Advanced Renal Cell Carcinoma (ARCC) trial. METHODS: Follow-up was divided into 11 time intervals; Kaplan-Meier estimates for not being censored were estimated for each interval. The QAS for each interval was weighted by the inverse probability of not being censored in that interval. Overall treatment-associated QAS was calculated as the sum of the weighted QAS across all follow-up intervals. Differences in mean QAS between temsirolimus and IFN-alfa were evaluated with t-statistics at a two-sided α = 0.05. RESULTS: In total, 416 patients were randomly assigned to temsirolimus (n = 209) or IFN-alfa (n = 207); 400 patients were included in this analysis. Overall weighted mean (standard deviation) QAS during progression-free survival was 111.9 (5.3) days with temsirolimus (n = 204) and 75.7 (6.3) days with IFN-alfa (n = 196). The mean weighted QAS difference of 36.2 days in favor of temsirolimus was significant (p < 0.05). LIMITATIONS: One potential limitation is that the weights developed by the Kaplan-Meier estimates did not allow for covariates to be adjusted among treatment arms. Another possible limitation is that the ARCC trial included patients with advanced renal cell carcinoma, and thus it cannot be conclusively determined how our findings would apply to patients with less advanced disease. CONCLUSIONS: Patients with poor-prognosis advanced renal cell carcinoma treated with temsirolimus had an incremental gain of 48% (36.2 days) in QAS compared with patients treated with IFN-alfa.

[Cost effectiveness in the Danish health care of ezetemibe co-administration compared to simvastatin]. / Omkostningseffektivitet i det danske sundhedsvaesen ved ezetimibe-koadministration med simvastatin.

INTRODUCTION: The purpose of this analysis is to evaluate the cost effectiveness of ezetemibe coadministration compared to a shift to higher doses of simvastatin or to a more potent statin. MATERIALS AND METHODS: The calculations are based on a Markov model in which a patient who does not attain the desired cholesterol outcome with simvastatin treatment is treated either with ezetemibe coadministration, or with increased simvastatin doses, or with a more potent statin. Calculations are conducted for a total of 72 different patient types followed over the remainder of their lives. RESULTS: Ezetemibe coadministration evaluated over the entire lifetime will be somewhat more expensive than simvastatin titration but must, however, be seen in relation to improved survival and increased quality of life. For the typical patient, treatment will be associated with costs of between DKK 50,000 and 100,000 per gained year of life, which cannot be deemed too expensive in relation to other interventions provided by the Health Authorities. For some patient types who receive treatment with a potent statin (atorvastatin), savings will also be possible here as well as an increase in life expectancy and quality of life. CONCLUSION: The results of the study indicate that ezetemibe coadministration is cost effective. The results are sustainable even with quite significant changes of the estimates used and taking into account uncertainties in the material and methods.

Cost effectiveness of adding ezetimibe to atorvastatin therapy in patients not at cholesterol treatment goal in Canada.

INTRODUCTION: This analysis compared the cost effectiveness of adding ezetimibe to atorvastatin therapy versus atorvastatin titration or adding cholestyramine (a resin) for patients at high risk of a coronary artery disease (CAD) event who did not reach target cholesterol levels on their current atorvastatin dosage. The primary analysis focused on 65-year-old patients with low-density lipoprotein cholesterol (LDL-C) levels of 3.1 or 3.6 mmol/L with a treatment goal of <2.5 mmol/L, classified as very high risk according to the 2000 Canadian Guidelines for Management and Treatment of Hyperlipidaemia. METHODS: A previously developed Markov model was utilised to capture the cost and clinical consequences of lipid-lowering therapy in primary and secondary prevention of CAD. Comparisons between treatment strategies were made using ICERs (cost per QALY) from a Canadian Ministry of Health perspective. The effects of lipid-lowering therapies were based on clinical trial data. The risks of CAD events were estimated using Framingham Heart Study risk equations. Treatment costs and the costs of acute and long-term care for CAD events were included in the analysis. Costs (Canadian dollar, 2002 values) and outcomes were discounted at 5% per annum. RESULTS: Ezetimibe added to atorvastatin therapy compared with treatment with the most common fixed atorvastatin daily dosage (10 mg) or with common atorvastatin titration strategies (up to 20 mg daily; up to 40 mg daily) resulted in cost per QALY estimates ranging from 25,344 to 44,332 Canadian dollars. The addition of ezetimibe to atorvastatin therapy was less costly and more effective than the addition of cholestyramine (dominant). CONCLUSION: Our analysis suggests that adding ezetimibe to atorvastatin for patients not achieving treatment goals with their current atorvastatin dose produces greater clinical benefits than treatment with a fixed-dose atorvastatin or atorvastatin titration at an increased overall cost. The cost-effectiveness ratios provide strong evidence for the adoption of ezetimibe within the Canadian healthcare system.

Lipid-modifying therapy and attainment of cholesterol goals in Europe: the Return on Expenditure Achieved for Lipid Therapy (REALITY) study.

BACKGROUND: Few studies have been conducted in actual clinical practice settings to evaluate the ways in which dyslipidemia is managed using lipid-modifying therapies. OBJECTIVE: To determine lipid-modifying therapy practices and their effects on low-density lipoprotein cholesterol (LDL-C) and/or total cholesterol (TC) goal attainment in Europeans based on prevailing guidelines at the time of therapy in each country. METHODS: Retrospective cohort analysis involving 58,223 patients initiated on lipid-modifying therapies in 10 European countries, with a median patient follow-up on lipid-modifying therapy of 15.3 months. Data on prescriptions of lipid-modifying therapies, laboratory data including LDL-C and TC, achievement of cholesterol goals for LDL-C and/or TC, and hospitalizations were obtained from healthcare administrative databases and/or patient chart reviews. RESULTS: Across Europe, statin monotherapy was the initial lipid-modifying treatment in 51,786 (89.3%) of 58,009 patients with available data. In addition, 38,853 (89.5%) of 43,410 patients with available follow-up statin potency data were initiated on statin regimens of medium or lower equipotency. Low-equipotency regimens include atorvastatin 5 mg, simvastatin 10 mg, and pravastatin 20 mg, whereas medium-equipotency regimens include atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg. Regimens were adjusted to higher equipotency via either up-titration or switches to combination regimens in 16.2% of patients. On average, 40.5% of patients across Europe who were not initially at guideline recommended cholesterol goals (either LDL-C or TC) and had follow-up data attained recommended cholesterol levels, including <30% of patients in Spain, Italy, or Hungary. In many countries, the likelihood of goal attainment was inversely associated with baseline cardiovascular risk and/or LDL-C levels. CONCLUSIONS: Lipid management strategies in Europe during the study period were dominated by statin monotherapy. Even after prolonged follow-up on lipid-modifying therapy, approximately 60% of Europeans studied did not achieve guideline recommended cholesterol goals. Future emphasis must be placed on subsequent lipid panel monitoring, as well as the use of more efficacious, well-tolerated lipid-modifying therapies such as dual cholesterol inhibitors to enable more European patients to attain their recommended cholesterol goals.

Cumprimento de metas com redutores de colesterol: Braço brasileiro do estudo cometa / Fulfillment of goals with cholesterol reducers: brazilian arm of Cometa study

A porcentagem de pacientes em uso de medicamentos hipolipemiantes, que atingem as metas de LDL-C propostas pelo NCEP ATP III, foi analisada nesse estudo prospectivo. Após seleção prévia, participaram do protocolo 20 médicos (cinco cardiologistas, cinco endocrinologistas e 10 clínicos gerais), que incluíram um total de 120 pacientes dislipêmicos em uso de hipolipemiantes nun período superior a 12 semanas. Os pacientes foram divididos em três categorias de risco (segundo o escore de Framingham): baixo risco ou categoria A (risco absoluto de coronariopatia < 10 por cento em 10 anos): risco moderado ou categoria B (risco absoluto de coronariopatia entre 10 por cento e 20 por cento em 10 anos) e alto risco ou categoria C (pacientes com DAC ou equivalente de DAC e risco absoluto de coronariopatia > 20 por cento em 10 anos). As metas de LDL-C foram definidas como: < 160mg/dl para o grupo de baixo risco, < 100mg/dl para o grupo de risco moderado e < 100mg/dl para o grupo de alto risco. A idade dos pacientes variou de 26 a 90 anos (média = 56 ± 13 anos) e 52 por cento era do sexo feminino. Na fase inicial do estudo, 93 por cento dos pacientes recebiam vastatinas e 7 por cento fibratos. A sinvastatina e a atorvastatina, nas doses médias de 12 e 26mg/dia, respectivamente, foram as bastatinas mais utilizadas e, com essas doses, 41 por cento dos pacientes atingiram as metas de LDL-C. Esse percentual aumentou para 46 por cento ao final do estudo, em conseqüência do ajuste das doses das vastatinas. As maiores porcentagens de sucesso foram observadas entre o spacientes de baixo risco e os resultados não foram influenciados pela especialidade do médico. Os achados desse estudo indicam que as porcentagens de pacientes que alcançam as metas de LDL-C estabelecidas pelas diretrizes são baixas

Cost of care for patients treated with lipid-lowering drugs.

OBJECTIVE: To investigate the relationship between attainment of treatment goals with lipid-lowering therapy and healthcare costs. PARTICIPANTS: 9789 patients who received treatment with a lipid-lowering agent at any time between 1 January 1993 and 14 April 2003. DESIGN AND METHODS: A cohort study using linkage of patient medical records from 29 Swedish primary care centres and the Swedish national inpatient register. The primary outcomes of interest were the total costs of medical care and costs of cardiovascular-related inpatient care during the year before treatment initiation and during years 1, 2 and 3 of treatment. The cost data were analysed with a two-part random-effects regression model. RESULTS: Of the 9789 patients identified in the database for the study, 6316 had at least one cholesterol measurement during the year after the index prescription and were included in the analysis. 37% of the patients attained the goal of low-density lipoprotein cholesterol < 3.0 mmol/L and total cholesterol < 5.0 mmol/L. Patients who attained treatment goal had 44% higher pre-treatment costs of care. During the first year of treatment, patients who attained treatment goal had 28% higher costs of care. After the first year, costs for goal-attaining patients were 17% higher. However, the cost of cardiovascular-related inpatient care in patients attaining cholesterol treatment goal was twice as high as in patients not achieving goal before treatment start and 40% lower 2-3 years after treatment start. CONCLUSION: Patients reaching target cholesterol levels showed a trend of cost reductions over time, whereas no such trend could be found for patients not reaching goal levels. Reductions in costs were substantial for cardiovascular-related inpatient care for patients attaining cholesterol goals compared with patients not attaining cholesterol goals.

Development and validation of a model to project the long-term benefit and cost of alternative lipid-lowering strategies in patients with hypercholesterolaemia.

INTRODUCTION: Patients not currently reaching their lipid goals, even with the use of statins, are at elevated coronary heart disease (CHD) risk. Ezetimibe, when coadministered with a patient's current statin, has been shown to effectively reduce cholesterol in patients with hypercholesterolaemia. In order to help healthcare decision makers assess the cost effectiveness of this treatment strategy, a model is needed to compare ezetimibe coadministration versus alternative statin titration strategies among patients who have failed to reach their lipid goal with their current statin dose. METHODS: A flexible decision-analytic model that projects the long-term benefit and cost of alternative lipid-lowering strategies is described. Using a Markov process, the model allows movement from one health state to another based on the predicted risk of CHD events (fatal and nonfatal) and the risk of death from non-CHD causes. Each health state can be assigned a quality-of-life weight and an expected cost in order to determine the total survival time, quality-adjusted survival time and cost associated with the alternative treatment strategies. The accuracy of the model in projecting the percentage of patients who experience fatal and nonfatal CHD events was assessed by using individual baseline patient characteristics from two long-term outcomes trials: the Air Force Coronary Atherosclerosis Prevention Study, a primary prevention trial, and the Scandinavian Simvastatin Survival Study, a secondary prevention trial. RESULTS: Compared with event rates in the two outcome trials, the model appears to underestimate both the absolute risk of nonfatal CHD events and its reduction due to lipid lowering. But the model appears to provide reasonable estimates of the absolute reduction in fatal CHD events following lipid treatment. DISCUSSION: The model will allow one to assess the cost effectiveness of alternative treatment strategies for hypercholesterolaemia including statin titration and the coadministration of ezetimibe in patients who have failed to reach their lipid goal with a statin. Because the benefit of reducing nonfatal CHD events may be underestimated, the model may overestimate the cost-effectiveness ratio of ezetimibe coadministration.

Cost-effectiveness of ezetimibe coadministration in statin-treated patients not at cholesterol goal: application to Germany, Spain and Norway.

BACKGROUND: Despite the growing use of statins, many hypercholesterolaemic patients fail to reach their lipid goal and remain at elevated risk of coronary heart disease (CHD). Alternative treatment strategies, such as ezetimibe coadministration and statin titration, can help patients achieve greater lipid control, and thereby lower their CHD risk. But is it cost effective to more aggressively lower cholesterol levels across a broad range of current statin users? METHODS: Using a decision-analytic model based on epidemiological and clinical trials data, we project the lifetime benefit and cost of alternative lipid-lowering treatment strategies for CHD and non-CHD diabetic patients in Germany, Spain and Norway. RESULTS: It is projected that from 40% to 76% of these patients who have failed to reach their lipid goal with their current statin treatment will be able to reach their goal with ezetimibe coadministration; this represents a gain of up to an additional absolute 14% who will be able to reach their goal compared with a 'titrate to goal' strategy where patients are titrated in order to reach their lipid goal (up to the maximum approved dose). For CHD patients, the estimated incremental cost-effectiveness ratio for ezetimibe coadministration is under Euro 18 000 per life-year gained (Euro/LYG) and 26 000 Euro/LYG compared with strategies based on the observed titration rates and the aggressive 'titrate to goal' strategy, respectively; for non-CHD diabetic patients, these ratios are under 26 000 Euro/LYG and 48 000 Euro/LYG for ezetimibe coadministration compared with the two titration strategies. CONCLUSION: Compared with statin titration, ezetimibe coadministration is projected to be cost effective in the populations and countries studied.

Cost, morbidity, and control of asthma in Hungary: The Hunair Study.

OBJECTIVE: To assess asthma-related morbidity, symptom control, and societal cost of asthmatic patients in Hungary. Secondary objective was to assess the relationship between asthma symptom control and costs incurred. METHODS: Three hundred seventy-eight pediatric asthma patients (6-14 years of age) and 711 adult asthma patients (18-55 years of age) in 19 pulmonary clinics were interviewed by their physicians regarding asthma-related drug therapy and recent (past 2 weeks) asthma morbidity (daytime asthma symptoms, nocturnal symptoms, limitation in daily activities resulting from asthma and asthma exacerbation). Physicians estimated patients' level of asthma control based on the Global Initiative of Asthma guidelines. Direct and indirect costs for asthma-related resources were determined based on patient reported 6 months' data except for drug costs that were based on patient reported 2 weeks of data. All cost data were annualized. RESULTS: Patients in the study were mostly prescribed inhaled controller medications for asthma symptom management (76.2% pediatric and 92.3% adult) during the 2 weeks preceding the survey. Asthma-related morbidity was experienced by 15% of pediatric patients and 30% of the adult patients at least once during the 2 weeks preceding the survey. Physician classified 69% of pediatric patients as having good control, 27.5% as having moderate control, and 2.8% as having poor control of their asthma. In the adult population, 50.7% were classified as having good control, 36.6% as having moderate control, and 12.7% as having poor control. The average total annual costs (direct and indirect costs) per patient were 833 EUR (897 USD) for pediatric patients and 632 EUR (681 USD) for adult patients. In both pediatric and adult patients the total costs were highest for patients with poor asthma control. The total cost per patient increased in the ratios of 1 to 1.4 to 2.4 for pediatric patients and 1 to 1.5 to 2.9 for adult patients with good, moderate, and poor control of asthma, respectively. CONCLUSION: Inhaled corticosteroids was the most frequent treatment prescribed for asthma patients in the study. However, patients reported substantial asthma-related morbidity. Children used more resources than adults, despite being classified as having better control. Patients with poor control of asthma symptoms incurred the highest societal cost, improving patient control may reduce cost to society by 40% or more.

National economic impact of tirofiban for unstable angina and myocardial infarction without ST elevation; example from the United Kingdom.

BACKGROUND: Acute coronary syndromes without ST elevation are a major health and economic burden. Treatments such as glycoprotein IIb/IIIa antagonists like tirofiban reduce the risk of complications but the cost impact of these agents including cost offsets of avoiding complications are needed particularly in Europe. METHODS: We used treatment patterns from the Prospective Registry of Acute Ischemic Syndromes in the UK, risk reductions derived from the PRISM-PLUS trial and cost estimates from the CHKS database to estimate the impact of tirofiban on PRAIS-UK patients with and without complications and subgroups at higher risk of complications. These subgroups (and proportions) were patients: (1) aged 60 or over with abnormal electrocardiograms (58%), (2) with ST depression or bundle branch block on admission (30%) and (3) with ST depression, bundle branch block or MI on admission (37%). RESULTS: Total cost of care in the UK at 6 months for the estimated 87339 acute coronary syndromes admissions annually was pound 213 million, which would increase by pound 33 million (15.7%) if tirofiban were given to all patients, avoiding 2422 complications at a mean cost per event avoided of pound 13388. Among the subgroups, the mean cost per event avoided ranges from pound 10856 for subgroup 1 to pound 5953 for subgroup 3. Treating the latter subgroup, would avoid 1977 events at a cost of pound 12 million (5.5%). CONCLUSION: The use of tirofiban in the UK to treat acute coronary syndromes patients without ST elevation provides an important therapeutic advantage at modest proportional increase in cost, particularly if targeted to higher risk subgroups as recommended in the European guidelines.