Cost Effectiveness of Paricalcitol versus a non-selective vitamin D receptor activator for secondary hyperparathyroidism in the UK: a chronic kidney disease markov model.

BACKGROUND: secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD) and a frequent cause of clinically significant bone disease. Non-selective vitamin D receptor (VDR) activator treatment has been used to treat the condition but is ineffective for many patients with hypercalcaemia and hyperphosphataemia and may precipitate worsening of their condition. Compared with non-selective VDR activator treatment, use of the VDR ligand paricalcitol may increase survival and reduce the risk of morbidities in patients with SHPT, which may have health economic consequences. OBJECTIVE: the objective of this study was to determine the cost effectiveness of paricalcitol versus a non-selective VDR activator for the treatment of SHPT in patients with CKD in the UK setting. METHODS: A Markov process model was developed employing data sources from the published literature, paricalcitol clinical trials and observational studies, official UK price/tariff lists and national population statistics. The comparator was alfacalcidol, a non-selective VDR activator medication. The primary perspective of the study was that of the UK National Health Service (NHS). The efficacy outcomes (reductions in SHPT, proteinuria, complications and mortality) were extrapolated to: number of life-years gained (LYG) and number of quality-adjusted life-years (QALYs). Clinical and economic outcomes were discounted at 3.5%. The year of costing for costs determined in the study was 2006. RESULTS: the reference case analysis was a 10-year time horizon, based on a comparison of paricalcitol with a non-selective VDR activator, which is started in CKD stage 3 (moderate reduction in glomerular filtration rate [GFR] with kidney damage) and continued in CKD stage 4 (severe reduction in GFR) and CKD stage 5 (established kidney failure). The use of paricalcitol leads to an additional medical cost of pound3224 ($US5970). The health benefits of paricalcitol lead to an increase in LYG of 0.52 and a gain in QALYs of 0.465. Therefore the use of paricalcitol results in an incremental cost-effectiveness ratio of pound6933/QALY ($US12 840/QALY) from the primary perspective of the NHS. One-way sensitivity analyses and probabilistic sensitivity analyses confirmed the robustness of the model. CONCLUSION: this model showed that the favourable clinical benefit of paricalcitol results in positive short- and long-term health economic benefits. This study suggests that the use of paricalcitol in patients with early CKD may be cost effective from the UK NHS perspective versus non-selective VDR activator medication.

Association of secondary hyperparathyroidism with CKD progression, health care costs and survival in diabetic predialysis CKD patients.

BACKGROUND/AIMS: The objective of this study was to examine health care costs and utilization and the risks of dialysis or mortality among diabetic predialysis chronic kidney disease (CKD) patients with and without secondary hyperparathyroidism (SHPT). METHODS: This retrospective, matched cohort study examined insurance claims from 703 adult diabetic predialysis CKD patients with and without SHPT during a 72-month follow-up period. Annualized estimates of health care service utilization, costs and disease progression to dialysis or death following index CKD diagnosis were compared. RESULTS: Preindex (baseline) characteristics were similar between the cohorts. Postindex numbers of prescription utilization, outpatient service utilization and hospitalizations were all higher (p < 0.0001) in diabetic CKD patients with SHPT compared to those without SPHT in both unadjusted and adjusted analyses even after multivariate adjustment for known confounders. The rate of progression to dialysis or death was higher for diabetic CKD patients with SHPT compared to those without SPHT. Those with SHPT were at higher risk of requiring dialysis treatment [hazard ratio (HR) = 6.7; 95% confidence interval (CI) = 4.3-10.6] and death (HR = 2.3; 95% CI = 1.1-4.9) compared to those without SHPT. CONCLUSION: In diabetic predialysis CKD patients, the presence of SHPT is associated with significantly greater health care resource utilization and costs, and a faster rate of disease progression.

The costs of treating acute heart failure: an economic analysis of the SURVIVE trial.

OBJECTIVE: To estimate the incremental cost per life year gained with levosimendan relative to dobutamine in treatment of acute heart failure based on the Survival of Patients with Acute Heart Failure in Need of Intravenous Inotropic Support (SURVIVE) trial. METHODS: SURVIVE enrolled 1,327 patients (levosimendan 664, dobutamine 663) from nine nations with 180-day survival from date of randomisation as the primary endpoint. Hospital resource utilisation was determined via clinical case reports. Unit costs were derived from hospital payment schedules for France, Germany and the UK, and represent a third-party payer perspective. Cost-effectiveness analysis was performed for a subset of the SURVIVE patient population selected in accordance with current levosimendan labeling. RESULTS: Mortality in the levosimendan group was 26 versus 28% for dobutamine (hazard ratio 0.91, 95% confidence interval 0.74-1.13, p=0.40). Initial hospitalisation length of stay was identical (levosimendan 14.4, dobutamine 14.5, p=0.98). Slightly lower rates of readmission were observed for levosimendan relative to dobutamine at 31 (p=0.13) and 180 days (p=0.23). Mean costs excluding study drug were equivalent for the index admission (levosimendan euro5,060, dobutamine euro4,952; p=0.91) and complete episode (levosimendan euro5,396, dobutamine euro5,275; p=0.93). CONCLUSION: At an acquisition cost of euro600 per vial, there is at least 50% likelihood that levosimendan is cost effective relative to dobutamine if willingness to pay is equal to or greater than euro15,000 per life year gained.

Assessment of clinical and economic benefits of weight management with sibutramine in general practice in Germany.

Obesity is associated with major health risks and a high economic burden impacting on health care systems. This study utilises the latest evidence from randomised clinical trials (RCTs) to explore and to assess the cost effectiveness of sibutramine in combination with diet and lifestyle advice compared to diet and lifestyle advice alone for the treatment of obese subjects without comorbidities at baseline in Germany. New evidence from recently published RCTs and post-marketing surveillance studies, including health economic data as well as quality of life (QoL) data, were used to model the long-term outcomes of weight management with sibutramine in German practice. German healthcare costs and new data from over 8,000 patients were analysed based on a recently published model. These new RCT data were used to model weight losses, proportion of responders to treatment, utilities by weight loss and variability in weight regain post-treatment. Costs and QoL benefits associated with weight loss (using SF-36 data from sibutramine trials), reduced incidence of coronary heart disease (using Framingham equations) and diabetes were used to estimate the cost per quality adjusted life year of sibutramine treatment. For 1,000 patients treated with sibutramine for 1 year, extrapolating outcomes over 4 further years, sibutramine is estimated to save 4.18 CHD events, 2.58 diabetes incident cases and give 51.5 more quality-adjusted life years (QALYs). The cost-utility analysis (CUA) estimates 13,706 euro per QALY gained. Results are sensitive to changes in weight loss, rate of weight regain and discounting rate. Although the non-pharmacological weight management programme in the comparator arm yielded higher weight losses than generally observed in clinical practice, these results demonstrate that additional sibutramine treatment is a cost effective therapy for an obese population without comorbidities in Germany. The CUA results are within the range generally accepted as cost effective and should be viewed as conservative when generalizing to settings offering standard non-pharmacological treatment.

Health-economic comparison of paricalcitol, calcitriol and alfacalcidol for the treatment of secondary hyperparathyroidism during haemodialysis.

This study evaluated the health-economic consequences of use of intravenous paricalcitol (Zemplar), oral calcitriol or oral and intravenous alfacalcidol for the treatment of patients with secondary hyperparathyroidism, focusing on a third-party payer perspective through inclusion of medication and hospital costs, survival rates and utilities. Cost values were based on German treatment recommendations and prices. Reference values for survival rates and utilities were based on the results of a MEDLINE search. The analysis showed a clear advantage for intravenous paricalcitol with respect to costs, effectiveness and utilities compared with treatment with oral calcitriol or intravenous alfacalcidol. Since the results were very cost sensitive with respect to selected diagnosis-related groups (DRGs) for kidney disease with dialysis, a sensitivity analysis was performed. This demonstrated first-order dominance of intravenous paricalcitol for a wide range of hospitalisation costs. In conclusion, this analysis suggested a clear benefit from the perspective of a third-party payer for intravenous paricalcitol compared with oral calcitriol and intravenous alfacalcidol in the treatment of patients with secondary hyperparathyroidism.

Hospital costs for treatment of acute heart failure: economic analysis of the REVIVE II study.

BACKGROUND: Acute heart failure (AHF) is the leading cause of hospital admission among older Americans. The Randomized EValuation of Intravenous Levosimendan Efficacy (REVIVE II) trial compared patients randomly assigned to a single infusion of levosimendan (levo) or placebo (SOC), each in addition to local standard treatments for AHF. We report an economic analysis of REVIVE II from the hospital perspective. METHODS: REVIVE II enrolled patients (N = 600) hospitalized for treatment of acute decompensated heart failure (ADHF) who remained dyspneic at rest despite treatment with intravenous diuretics. Case report forms documented index hospital treatment (drug administration, procedures, days of treatment by care unit), as well as subsequent hospital and emergency department admissions during follow-up ending 90 days from date of randomization. These data were used to impute cost of admission based on an econometric cost function derived from >100,000 ADHF hospital billing records selected per REVIVE II inclusion criteria. RESULTS: Index admission mean length of stay (LOS) was shorter for the levo group compared with standard of care (SOC) (7.03 vs 8.96 days, P = 0.008) although intensive care unit (ICU)/cardiac care unit (CCU) days were similar (levo 2.88, SOC 3.22, P = 0.63). Excluding cost for levo, predicted mean (median) cost for the index admission was levo US $13,590 (9,458), SOC $19,021 (10,692) with a difference of $5,431 (1,234) favoring levo (P = 0.04). During follow-up through end of study day 90, no significant differences were observed in numbers of hospital admissions (P = 0.67), inpatient days (P = 0.81) or emergency department visits (P = 0.41). Cost-effectiveness was performed with a REVIVE-II sub-set conforming to current labeling, which excluded patients with low baseline blood pressure. Assuming an average price for levo in countries where currently approved, there was better than 50% likelihood that levo was both cost-saving and improved survival. Likelihood that levo would be cost-effective for willingness-to-pay below $50,000 per year of life gained was about 65%. CONCLUSIONS: In the REVIVE II trial, patients treated with levo had shorter LOS and lower cost for the initial hospital admission relative to patients treated with SOC. Based on sub-group analysis of patients administered per the current label, levo appears cost-effective relative to SOC.

Chronic kidney disease Markov model comparing paricalcitol to calcitriol for secondary hyperparathyroidism: a US perspective.

OBJECTIVE: The objective of this study was to determine the cost effectiveness of paricalcitol versus calcitriol for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease in the United States setting. METHODS: A Markov process model was developed employing data sources from the published literature, paricalcitol clinical trials and observational studies, official US price/tariff lists and national population statistics. The comparator was calcitriol, a non-selective vitamin D receptor activator (VDRA) medication. The primary perspective of the study was that of the third-party payer in the US. The efficacy outcomes (reduction in secondary hyperparathyroidism (SHPT), reduction in proteinuria, complications and mortality) were extrapolated to: number of life-years gained (LYG) and number of quality-adjusted life-years (QALYs). Clinical and economic outcomes were discounted at 3.5%. RESULTS: The reference case analysis was a 10-year time horizon based on a comparison of paricalcitol with calcitriol, which is started in chronic kidney disease (CKD) stage 3 and continued in CKD stage 4 and CKD stage 5. The use of paricalcitol leads to a cost saving of US$1941. The inclusion of indirect costs leads to a cost saving of US$2528. The use of paricalcitol leads to an increase in life-years gained (0.47 years) and a gain in QALYs (0.43). The use of paricalcitol results in a dominant outcome from the perspective of the third-party payer, as well as from the societal perspective. One-way sensitivity analyses and probabilistic sensitivity analyses confirmed the robustness of the model. CONCLUSION: This model showed that the favorable clinical benefit of paricalcitol results in positive short and long-term health economic benefits. This study suggests that the use of paricalcitol in patients with early chronic kidney disease may be cost-effective from the third-party payer perspective in the US versus calcitriol. Additional comparative studies are necessary to validate these results.

Impact of secondary hyperparathyroidism on disease progression, healthcare resource utilization and costs in pre-dialysis CKD patients.

BACKGROUND AND OBJECTIVES: Secondary hyperparathyroidism (SHPT) can lead to significant morbidity, mortality, and additional healthcare resource utilization in chronic kidney disease (CKD) stage 5. The objective of this study was to examine healthcare costs and utilization, and the risks of dialysis or mortality, among pre-dialysis CKD patients with and without SHPT. RESEARCH DESIGN AND METHODS: This retrospective cohort study examined insurance claims from 66 644 adult, pre-dialysis, CKD patients with and without SHPT during a 72-month period. Annualized estimates of healthcare costs and utilization, and disease progression to dialysis or death following index CKD diagnosis were compared. RESULTS: Post-index annualized costs and inpatient healthcare resource utilization was higher in those with SHPT in both unadjusted and adjusted (controlling for gender, age, plan type, payer type, geographic region, physician specialty, pre-index co-morbidities, and pre-index total healthcare costs), and unmatched and matched analyses. Kaplan-Meier analysis demonstrated that the rate of progression to dialysis or death was higher for CKD with SHPT compared to CKD without SHPT, and Cox proportional hazard models suggested that CKD patients with SHPT were more than four to five times as likely to initiate dialysis or die as compared to CKD without SHPT. CONCLUSION: SHPT in pre-dialysis CKD patients is associated with significantly greater healthcare costs, inpatient hospitalizations, and a faster rate of disease progression compared to pre-dialysis CKD without SHPT. Since observational studies are designed to demonstrate associations rather than causality, further investigation is required to confirm these findings.

Improvement and longterm maintenance of quality of life during treatment with adalimumab in severe rheumatoid arthritis.

OBJECTIVE: In patients with longstanding severe rheumatoid arthritis (RA) receiving chronic treatment with adalimumab, health related quality of life (HRQOL) was assessed using new instruments [Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-Fatigue) and Health Utilities Index Mark 3 (HUI3)] and a more conventional instrument [Medical Outcomes Study Short Form-36 Health Survey (SF-36)]. METHODS: Different measures for collecting patient-reported outcomes were applied simultaneously during the 3-year study period. Sociodemographic and medical history data were assessed at the baseline visit. Clinical examinations (e.g., joint examination and morning stiffness), disease assessments, and HRQOL data were recorded every 8 weeks. For dichotomous and categorical variables, absolute and relative frequencies were calculated. Metric measures were described using mean and standard deviation and/or standard error of the mean. HRQOL data were analyzed using observed cases. RESULTS: All assessed measures (FACIT-Fatigue, HUI3, SF-36) showed a rapid and statistically significant improvement from baseline following initiation of adalimumab therapy. This effect was maintained over the study period for a mean of 1.6 years in all applied measures. HRQOL data from all tested instruments were significantly correlated with each other. CONCLUSION: Chronic therapy with adalimumab improved measures of fatigue and HRQOL in patients with longstanding RA.