Etelcalcetide for Treating Secondary Hyperparathyroidism: An Evidence Review Group Evaluation of a NICE Single Technology Appraisal.

The manufacturer of the calcimimetic drug etelcalcetide was invited to make an evidence submission as part of the National Institute for Health and Care Excellence (NICE) Single Technology Appraisal (STA) programme. Within this submission, they reported evidence on the clinical and cost effectiveness of etelcalcetide for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) on haemodialysis. The Southampton Health Technology Assessments Centre (SHTAC), part of the Wessex Institute at the University of Southampton, was the independent Evidence Review Group (ERG) commissioned to appraise the company's submission. This article describes the ERG's review and critique of the company's submission and summarises the NICE Appraisal Committee's subsequent guidance (issued in June 2017). The clinical-effectiveness evidence submitted by the company consisted of two double-blind, randomised controlled trials (RCTs) comparing etelcalcetide with placebo, one RCT comparing etelcalcetide with cinacalcet, two single-arm extension studies of the above trials, and one single-arm study evaluating the effect of switching from cinacalcet to etelcalcetide. No study specifically examined the population specified in the NICE appraisal scope: patients refractory to standard therapy with phosphate binders and vitamin D (PBVD). None of these trials were designed to collect long-term efficacy data for outcomes such as mortality, bone fractures, cardiovascular events, or parathyroidectomies. Instead, biomarker data from the trials were mapped to long-term outcomes by an assumed linear relationship between the trial outcome, reduction of parathyroid hormone (PTH) by > 30%, and the log-hazard ratios for the occurrence of clinical events derived from a large, long-term RCT of cinacalcet (the EVOLVE trial). After submission of a confidential Patient Access Scheme (PAS) discount reducing etelcalcetide drug costs, the incremental cost-effectiveness ratio (ICER) for etelcalcetide versus cinacalcet was £14,778 per quality-adjusted life-year (QALY) gained in the company's base case. While this value is lower than the NICE threshold range of £20,000 and £30,000 per QALY gained, it was the opinion of the ERG that the ICER was highly uncertain due to efficacy data limitations for etelcalcetide, inadequate synthesis of clinical-effectiveness evidence, and strong assumptions connecting short-term biomarker data with long-term clinical outcomes. The ERG produced an alternative base case for etelcalcetide versus cinacalcet, with an ICER of £22,400 per QALY gained, also subject to uncertainty. The NICE Appraisal Committee recommended etelcalcetide as an option for the treatment of SHPT in adults with CKD only if treatment with a calcimimetic is indicated and cinacalcet is not suitable, subject to the company's provision of the agreed PAS discount.

A Decision-Analytic Model to Assess the Cost-Effectiveness of Etelcalcetide vs. Cinacalcet.

INTRODUCTION: Etelcalcetide is a novel intravenous calcimimetic for the treatment of secondary hyperparathyroidism (SHPT) in haemodialysis patients. The clinical efficacy and safety of etelcalcetide (in addition to phosphate binders and vitamin D and/or analogues [PB/VD]) was evaluated in three phase III studies, including two placebo-controlled trials and a head-to-head study versus the oral calcimimetic cinacalcet. OBJECTIVE: The objective of this study was to develop a decision-analytic model for economic evaluation of etelcalcetide compared with cinacalcet. METHODS: We developed a life-time Markov model including potential treatment effects on mortality, cardiovascular events, fractures, and subjects' persistence. Long-term efficacy of etelcalcetide was extrapolated from the reduction in parathyroid hormone (PTH) in the phase III trials and the available data from the outcomes study in cinacalcet (EVOLVE trial). Etelcalcetide was compared with cinacalcet, both in addition to PB/VD. We applied unit costs averaged from five European countries and a range of potential etelcalcetide pricing options assuming parity price to weekly use of cinacalcet and varying it by a 15 or 30% increase. RESULTS: Compared with cinacalcet, the incremental cost-effectiveness ratio of etelcalcetide was €1,355 per QALY, €24,521 per QALY, and €47,687 per QALY for the three prices explored. The results were robust across the probabilistic and deterministic sensitivity analyses. CONCLUSIONS: Our modelling approach enabled cost-utility assessment of the novel therapy for SHPT based on the observed and extrapolated data. This model can be used for local adaptations in the context of reimbursement assessment.

Cost-effectiveness analysis of paricalcitol versus calcitriol for the treatment of SHPT in dialytic patients from the SUS perspective.

Introduction: Secondary hyperparathyroidism (SHPT) is a consequence of chronic kidney disease. The treatment at the Brazilian Unified Heath System (SUS) is performed with calcitriol, a drug which favors hypercalcemia and/or hyperphosphatemia, hindering the control of SHPT. Another option is paricalcitol, which causes parathormone (PTH) suppression faster than calcitriol, with minor changes in calcium-phosphorus product and calcium and phosphorus serum levels. Objective: This study aims to develop a cost-effectiveness analysis of paricalcitol versus calcitriol for patients in dialytic treatment with SHPT, from the SUS perspective. Methods: A Markov decision model was developed for patients ≥ 50 years old with end stage renal disease in dialytic treatment and SHPT. Quarterly cycles and a lifetime time horizon were considered. Life years (LY) gained were assessed as clinical outcome. Clinical and economic inputs were obtained from systematic literature review and official databases. Costs are presented in Brazilian real (BRL), for the year 2014. Results: In the base case: paricalcitol generated a clinical benefit of 16.28 LY gained versus 14.11 LY gained with calcitriol, total costs of BRL 131,064 and BRL 114,262, respectively, determining an incremental cost-effectiveness ratio of BRL 7,740 per LY gained. The data robustness was confirmed by the sensitivity analysis. Conclusions: According to cost-effectiveness threshold recommended by the World Health Organization for 2013, the treatment of SHPT in patients on dialysis with paricalcitol is cost-effective when compared to calcitriol, from the public healthcare system perspective, in Brazil.

Introdução: O hiperparatireoidismo secundário (HPTS) é uma consequência da doença renal crônica. O tratamento no SUS é realizado com calcitriol, que favorece a hipercalcemia e/ou hiperfosfatemia, dificultando o controle do HPTS. Uma opção clinicamente relevante é o paricalcitol, que ocasiona a supressão do paratormônio (PTH) de forma mais rápida que o calcitriol e com menores alterações nas taxas séricas de cálcio, fósforo e do produto cálcio-fósforo. Objetivo: Este trabalho tem como objetivo desenvolver uma análise de custo-efetividade de paricalcitol versus calcitriol para pacientes em diálise com HPTS, perspectiva do SUS. Métodos: Foi desenvolvido um modelo de decisão de Markov para a população ≥ 50 anos, com DRC em diálise e HPTS. Foram considerados ciclos trimestrais e um horizonte temporal lifetime. O desfecho clínico avaliado foram os anos de vida ganhos. Dados foram obtidos a partir de revisão sistemática da literatura e bases de dados oficiais. Custos em reais (R$), ano de 2014. Resultados: No caso base: paricalcitol gerou benefício clínico de 16,28 anos de vida ganhos versus 14,11 anos de vida ganhos com calcitriol, custos totais de R$ 131.064 e R$ 114.262, respectivamente. A razão de custo-efetividade incremental de R$ 7.740 por ano de vida salvo. Dados robustos confirmados pela análise de sensibilidade. Conclusão: De acordo com o limiar de custo-efetividade recomendado pela Organização Mundial de Saúde para o ano de 2013, o tratamento de pacientes com HPTS em diálise com paricalcitol é custo-efetivo, comparado ao calcitriol, perspectiva SUS.

Cost-effectiveness analysis of paricalcitol versus calcitriol for the treatment of SHPT in dialytic patients from the SUS perspective / Análise de custo-efetividade de paricalcitol versus calcitriol no tratamento do HPTS em pacientes do SUS dialíticos, da perspectiva

Abstract Introduction: Secondary hyperparathyroidism (SHPT) is a consequence of chronic kidney disease. The treatment at the Brazilian Unified Heath System (SUS) is performed with calcitriol, a drug which favors hypercalcemia and/or hyperphosphatemia, hindering the control of SHPT. Another option is paricalcitol, which causes parathormone (PTH) suppression faster than calcitriol, with minor changes in calcium-phosphorus product and calcium and phosphorus serum levels. Objective: This study aims to develop a cost-effectiveness analysis of paricalcitol versus calcitriol for patients in dialytic treatment with SHPT, from the SUS perspective. Methods: A Markov decision model was developed for patients ≥ 50 years old with end stage renal disease in dialytic treatment and SHPT. Quarterly cycles and a lifetime time horizon were considered. Life years (LY) gained were assessed as clinical outcome. Clinical and economic inputs were obtained from systematic literature review and official databases. Costs are presented in Brazilian real (BRL), for the year 2014. Results: In the base case: paricalcitol generated a clinical benefit of 16.28 LY gained versus 14.11 LY gained with calcitriol, total costs of BRL 131,064 and BRL 114,262, respectively, determining an incremental cost-effectiveness ratio of BRL 7,740 per LY gained. The data robustness was confirmed by the sensitivity analysis. Conclusions: According to cost-effectiveness threshold recommended by the World Health Organization for 2013, the treatment of SHPT in patients on dialysis with paricalcitol is cost-effective when compared to calcitriol, from the public healthcare system perspective, in Brazil.

Resumo Introdução: O hiperparatireoidismo secundário (HPTS) é uma consequência da doença renal crônica. O tratamento no SUS é realizado com calcitriol, que favorece a hipercalcemia e/ou hiperfosfatemia, dificultando o controle do HPTS. Uma opção clinicamente relevante é o paricalcitol, que ocasiona a supressão do paratormônio (PTH) de forma mais rápida que o calcitriol e com menores alterações nas taxas séricas de cálcio, fósforo e do produto cálcio-fósforo. Objetivo: Este trabalho tem como objetivo desenvolver uma análise de custo-efetividade de paricalcitol versus calcitriol para pacientes em diálise com HPTS, perspectiva do SUS. Métodos: Foi desenvolvido um modelo de decisão de Markov para a população ≥ 50 anos, com DRC em diálise e HPTS. Foram considerados ciclos trimestrais e um horizonte temporal lifetime. O desfecho clínico avaliado foram os anos de vida ganhos. Dados foram obtidos a partir de revisão sistemática da literatura e bases de dados oficiais. Custos em reais (R$), ano de 2014. Resultados: No caso base: paricalcitol gerou benefício clínico de 16,28 anos de vida ganhos versus 14,11 anos de vida ganhos com calcitriol, custos totais de R$ 131.064 e R$ 114.262, respectivamente. A razão de custo-efetividade incremental de R$ 7.740 por ano de vida salvo. Dados robustos confirmados pela análise de sensibilidade. Conclusão: De acordo com o limiar de custo-efetividade recomendado pela Organização Mundial de Saúde para o ano de 2013, o tratamento de pacientes com HPTS em diálise com paricalcitol é custo-efetivo, comparado ao calcitriol, perspectiva SUS.

Budget impact of secondary hyperparathyroidism treatment in chronic kidney disease in an Ecuadorian social security hospital.

BACKGROUND: Chronic kidney disease (CKD) is a disorder with high morbidity and mortality worldwide whose complications generate multiple costs. In Ecuador, only a few healthcare institutions have implemented management protocols aimed to reduce costs and to improve the quality of life of patients. The aim of this study is to evaluate the short-term (1-year) and long-term (5-year) costs and savings in the management of secondary hyperparathyroidism (SHPT) of hemodialyzed CKD patients by comparing calcitriol and paricalcitol in a large social security hospital in Quito, Ecuador. METHODS: The estimation model assessed the resources used in the management of SHPT by comparing prospectively the cost savings within 1-year and 5-year time horizon with calcitriol and paricalcitol. Hospitalization, erythropoietin (EPO), treatment doses, intravenous iron consumption, and medical supplies were estimated according international references, based on the initial parathormone level (iPTH) of patients. The Ecuadorian National Reference costs (2014-2015) and institutional costs were used to calculate treatment costs. A statistical sensitivity analysis was also performed. RESULTS: The study was based on data from 354 patients of whom 147 (41.4 %) had a value of iPTH in the range 300-600 pg/ml, 45 (12.8 %) in the range 601-800 pg/ml, and 162 (45.7 %) over 800 pg/ml. The 1-year estimated costs per patient for calcitriol and paricalcitol, respectively, were: medication, 63.88 USD and 1,123.44 USD; EPO, 19,522.95 USD and 16,478 USD; intravenous iron 143.21 USD and 187.76 USD. Yearly hospitalization costs per patient were 11,647.99 USD with calcitriol and 8,019.41 USD with paricalcitol. Total yearly costs per patient amounted to 31,378.02 USD with calcitriol and 25,809.50 USD with paricalcitol. Total savings using paricalcitol were 5,568.52 USD per patient compared with calcitriol. The 5-year cumulative medication costs were 319 USD for calcitriol and 2,403 USD for paricalcitol; EPO with calcitriol was 97,615 USD and with paricalcitol 82,394 USD; intravenous iron with calcitriol was 716 USD and paricalcitol 939 USD. Hospitalization costs for patients with calcitriol and paricalcitol were 43,095 USD and 62,595 USD, respectively. Total savings using paricalcitol amounted 32,414 USD per patient compared with calcitriol. CONCLUSIONS: Paricalcitol use generated more cost savings than calcitriol after 1 and 5 years.

The cost-effectiveness of drug therapies to treat secondary hyperparathyroidism in renal failure: a focus on evidence regarding paricalcitol and cinacalcet.

The present review aims to assess the state-of-the-art regarding cost-effectiveness of therapy for secondary hyperparathyroidism in order to identify the best treatment and review methodological issues. PubMed and the Cochrane Library were searched to identify papers performing comparative analysis of costs and effects of treatment for secondary hyperparathyroidism in adult patients. Among the 66 papers identified, only 10 were included in the analysis. Treatment strategies evaluated in the selected papers were: cinacalcet in addition to vitamin D and phosphate binders versus vitamin D and phosphate binders only (seven papers), paricalcitol versus non-selective vitamin D (two papers), early and late introduction of cinacalcet in addition to vitamin D and phosphate binders (one paper) and paricalcitol versus cinacalcet (one paper). The high degree of heterogeneity among alternative treatments and methodological limits related to cost items considered, resource valuation methods and so on, make it unfeasible to reach a definite conclusion regarding cost-effectiveness but allow for future research opportunities.

Reforming medicare's dialysis payment policies: implications for patients with secondary hyperparathyroidism.

OBJECTIVE: To demonstrate how expanding services covered by a "bundled payment" can also expand variation in the costs of treating patients under the bundle, using the Medicare dialysis program as an example. DATA SOURCES/STUDY SETTING: Observational claims-based study of 197,332 Medicare hemodialysis beneficiaries enrolled for at least one quarter during 2006-2008. STUDY DESIGN: We estimated how resource utilization (all health services, dialysis-related services, and medications) changes with intensity of secondary hyperparathyroidism (sHPT) treatment. DATA EXTRACTION METHODS: Using Medicare claims, a patient-quarter level dataset was constructed, including a measure of sHPT treatment intensity. PRINCIPAL FINDINGS: Under the existing, narrow dialysis bundle, utilization of covered services is relatively constant across treatment intensity groups; under a broader bundle, it rises more rapidly with treatment intensity. CONCLUSIONS: The broader Medicare dialysis bundle reimburses providers uniformly, even though patients treated more intensively for sHPT cost more to treat. Absent any payment adjustments or efforts to ensure quality, this flat payment schedule may encourage providers to avoid high-intensity patients or reduce their treatment intensity. The first incentive harms efficiency. The second may improve or worsen efficiency, depending on whether it reduces appropriate or inappropriate treatment.

Comparison of oral and intravenous alfacalcidol in chronic hemodialysis patients.

BACKGROUND: Activated vitamin D is the mainstay of treatment for secondary hyperparathyroidism (SHPT) in chronic hemodialysis patients. However, the optimal route of administration is still debated. The aim of our study was to compare efficacy of oral vs intravenous (IV) administration of alfacalcidol in hemodialysis. A secondary objective was to determine the cost-effectiveness advantage of oral administration. METHODS: Eighty-eight chronic hemodialysis patients receiving IV alfacalcidol three times a week were included in the study. All were switched to the same dose of alfacalcidol given orally three times a week during the hemodialysis session. A budget impact analysis was performed. RESULTS: Mean patient age was 64 years old and 43% were males. The mean alfacalcidol dose administered was 2.1 µg three times a week. After three months, serum parathormone (PTH) levels decreased from 80 to 59 pmol/L (p = 0.001) and total serum calcium levels increased from 2.34 to 2.40 mmol/L (p = 0.002). After six months, total serum calcium levels were still significantly higher. Alfacalcidol dosage was significantly decreased during study period; the mean reduction was 0.44 µg per dose. Finally, oral administration was associated with an annual cost reduction of 197 678$CAN and an annual nursing time reduction of 25 days. CONCLUSION: Our findings support that switching IV to oral administration of alfacalcidol during hemodialysis sessions may lead to a similar control of SHPT with lower doses of activated vitamin D. This is a good strategy for optimizing compliance and may allow a dose reduction because of a greater efficacy to suppress PTH. Oral administration also has significant cost-effectiveness advantages.

Assessment of resource use and costs associated with parathyroidectomy for secondary hyperparathyroidism in end stage renal disease in the UK.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) is a major complication of end stage renal disease (ESRD). For the National Health Service (NHS) to make appropriate choices between medical and surgical management, it needs to understand the cost implications of each. A recent pilot study suggested that the current NHS healthcare resource group tariff for parathyroidectomy (PTX) (£2071 and £1859 in patients with and without complications, respectively) is not representative of the true costs of surgery in patients with SHPT. OBJECTIVE: This study aims to provide an estimate of healthcare resources used to manage patients and estimate the cost of PTX in a UK tertiary care centre. METHODS: Resource use was identified by combining data from the Proton renal database and routine hospital data for adults undergoing PTX for SHPT at the University Hospital of Wales, Cardiff, from 2000-2008. Data were supplemented by a questionnaire, completed by clinicians in six centres across the UK. Costs were obtained from NHS reference costs, British National Formulary and published literature. Costs were applied for the pre-surgical, surgical, peri-surgical, and post-surgical periods so as to calculate the total cost associated with PTX. RESULTS: One hundred and twenty-four patients (mean age=51.0 years) were identified in the database and 79 from the questionnaires. The main costs identified in the database were the surgical stay (mean=£4066, SD=£,130), the first month post-discharge (£465, SD=£176), and 3 months prior to surgery (£399, SD=£188); the average total cost was £4932 (SD=£4129). From the questionnaires the total cost was £5459 (SD=£943). It is possible that the study was limited due to missing data within the database, as well as the possibility of recall bias associated with the clinicians completing the questionnaires. CONCLUSION: This analysis suggests that the costs associated with PTX in SHPT exceed the current NHS tariffs for PTX. The cost implications associated with PTX need to be considered in the context of clinical assessment and decision-making, but healthcare policy and planning may warrant review in the light of these results.

Cost effectiveness of paricalcitol versus cinacalcet with low-dose vitamin D for management of secondary hyperparathyroidism in haemodialysis patients in the USA.

BACKGROUND: The IMPACT SHPT [Improved Management of Intact Parathyroid Hormone (iPTH) with Paricalcitol-Centered Therapy Versus Cinacalcet Therapy with Low-Dose Vitamin D in Hemodialysis Patients with Secondary Hyperparathyroidism] study compared the effectiveness of paricalcitol and cinacalcet in the management of secondary hyperparathyroidism in haemodialysis patients but did not report the costs or cost effectiveness of these treatments. AIM: The aim of this study was to compare the cost effectiveness of a paricalcitol-based regimen versus cinacalcet with low-dose vitamin D for management of secondary hyperparathyroidism in haemodialysis patients from a US payer perspective, using a 1-year time horizon. METHODS: This was a post hoc cost-effectiveness analysis of data collected for US patients enrolled in the IMPACT SHPT study-a 28-week, randomized, open-label, phase 4, multinational study (ClinicalTrials.gov identifier: NCT00977080). Patients eligible for the IMPACT SHPT study were aged≥18 years with stage 5 chronic kidney disease, had been receiving maintenance haemodialysis three times weekly for at least 3 months before screening and were to continue haemodialysis during the study. Only US patients who reached the evaluation period (weeks 21-28) were included in this secondary analysis. US subjects in the IMPACT SHPT study were randomly assigned to receive intravenous paricalcitol, or oral cinacalcet plus fixed-dose intravenous doxercalciferol, for 28 weeks. Patients in the paricalcitol group could also receive supplemental cinacalcet for hypercalcaemia. The primary effectiveness endpoint in the IMPACT SHPT study was the proportion of subjects who achieved a mean intact parathyroid hormone (iPTH) level of 150-300 pg/mL during the evaluation period. In this secondary analysis, we estimated the incremental cost-effectiveness ratio (ICER), comparing paricalcitol-treated patients with cinacalcet-treated patients on the basis of this primary endpoint and several secondary endpoints. Costs were estimated by examining the dosage of the study drug (paricalcitol or cinacalcet) and phosphate binders used by each participant during the trial. Nonparametric bootstrap analysis was used to examine the accuracy of the ICER point estimates. RESULTS: The percentages of patients achieving the treatment goal of a mean iPTH level between 150-300 pg/mL during weeks 21-28 of therapy were 56.9% in the paricalcitol group and 34.0% in the cinacalcet group (a difference of 23%, p=0.0235). Paricalcitol was also more effective for each of the secondary endpoints. When annualized, the total drug costs were US$10,153 in the paricalcitol group and US$15,967 in the cinacalcet group, a difference of US$5,814 (57.3%, p=0.0053). Because the paricalcitol-based treatment was less expensive and more effective, it was 'dominant', compared with cinacalcet, in this cost-effectiveness analyses. In our bootstrap analysis, 99.1% of bootstrap replicates for the ICER of the primary endpoint fell within the lower right quadrant of the cost-effectiveness plane-where paricalcitol is considered dominant. For all of the other endpoints, paricalcitol was dominant in 100% of replicates. CONCLUSION: On the basis of dosing and effectiveness data from US patients in the IMPACT SHPT study, we found that a regimen of intravenous paricalcitol was more cost effective than cinacalcet plus low-dose vitamin D in the management of iPTH in patients with SHPT requiring haemodialysis.

Cost per responder analysis in patients with secondary hyperparathyroidism on dialysis treated with cinacalcet.

BACKGROUND: Growing financial pressure on US dialysis providers requires economic efficiency considerations. The objective of this study was to examine short-term economic efficiencies of a cinacalcet-based treatment approach for secondary hyperparathyroidism. METHODS: This study retrospectively assessed cost per biochemical response of the OPTIMA trial. OPTIMA was conducted in end-stage renal disease patients to compare biochemical control in patients receiving cinacalcet in addition to vitamin D sterols and phosphate binders vs patients receiving vitamin D sterol and phosphate binders alone. It explored three laboratory measurement response definitions from baseline to week 23: (1) decreases in parathyroid hormone (PTH) ≥30%; (2) PTH ≤ 300 pg/ml; and (3) PTH ≤ 300 pg/mL, calcium <9.5 mg/dL and phosphorus <5.5 mg/dL. Medication use and costs were measured to calculate average costs and incremental cost per responder. Stratification by lower and higher baseline PTH assessed cost per response by disease severity. RESULTS: There were 38-77% more responders with cinacalcet vs control, depending on response definition. Mean (SD) per patient total medication costs were $5423 ($3698) for cinacalcet and $2633 ($2334) for control, leading to a mean difference of $2790 over 23 weeks. When response was defined as a decrease in PTH ≥ 30% from baseline, the average cost per responder was $11,266 for control vs $7027 for cinacalcet. The incremental cost per incremental responder ranged from $5186-$9168. Across all response measures, cost per responder was lower in patients with lower baseline PTH. CONCLUSIONS: Representing a more efficient allocation of economic resources over the short-term, cinacalcet-based treatment algorithm led to a lower cost per biochemical response, particularly in patients with lower disease severity, vs vitamin D sterols and phosphate binders alone. These findings should be interpreted alongside the study limitation of converting international trial-based medication utilization into US costs.

Comparative cost analysis of management of secondary hyperparathyroidism with paricalcitol or cinacalcet with low-dose vitamin D in hemodialysis patients.

OBJECTIVE: The objective of this analysis was to compare costs of paricalcitol or cinacalcet plus low dose vitamin D, and of phosphate binders, in patients in the IMPACT SHPT study; and to extrapolate those to estimate expected annual maintenance costs. METHODS: IMPACT SHPT was a 28-week, randomized, open-label trial. Subjects from 12 countries received intravenous (IV) or oral paricalcitol, or oral cinacalcet plus fixed IV doxercalciferol or oral alfacalcidol. The primary end-point was the proportion of subjects who achieved a mean intact parathyroid hormone (iPTH) value of 150-300 pg/mL during weeks 21-28 (evaluation period). This study compares the costs of study drugs and phosphate binders among participants during the study and annualized. This analysis includes only those subjects that reached the evaluation period (134 in each group). RESULTS: The mean total drug costs over the study period were €2606 (SD = €2000) in the paricalcitol group and €3034 (SD = €3006) in the cinacalcet group (difference €428, p = 0.1712). The estimated annualized costs were €5387 (SD = €4139) in the paricalcitol group and €6870 (SD = €6256) in the cinacalcet group (difference €1492, p = 0.0395). In addition, a significantly greater proportion (p = 0.010) of subjects in the paricalcitol arm (56.0%) achieved an iPTH of 150-300 pg/mL during the evaluation period compared to the cinacalcet arm (38.2%). LIMITATIONS: This was a secondary analysis of the IMPACT SHPT study which was not designed or powered for costs as an outcome. The dosing of study drugs and phosphate binders in the IMPACT study may not reflect actual practice, and patients were followed for 28 weeks, while the treatment of SHPT is long-term. CONCLUSION: Patients with SHPT requiring hemodialysis who were treated with a paricalcitol-based regimen for iPTH control had lower estimated annual drug costs compared to those treated with cinacalcet plus low-dose vitamin D.

Pharmacological control of secondary hyperparathyroidism in hemodialysis subjects: a cost consequences analysis of data from the FARO study.

BACKGROUND AND OBJECTIVES: Secondary hyperparathyroidism (SHPT) is a frequent complication of CKD with incidence, prevalence, and costs increasing worldwide. The objective of this analysis was to estimate therapy cost of SHPT in a sub-population of the FARO study. MATERIALS AND METHODS: In the FARO study, an observational survey aimed to evaluate patterns of treatment in patients with SHPT who had undergone hemodialysis, pharmacological treatments and biochemical parameters evolution data were collected in four surveys. Patients maintaining the same treatment in all sessions were grouped by type of treatment and evaluated for costs from the Italian National Health Service perspective. RESULTS: Four cohorts were identified: patients treated with oral (PO) calcitriol (n=182), intravenous (IV) calcitriol (n=34), IV paricalcitol (n=62), and IV paricalcitol+cinacalcet therapy (n=20); the cinacalcet monotherapy group was not analysed due to low number of patients (n=9). Parathyroid hormone (PTH) level at baseline and effectiveness of treatments in suppressing PTH level were assessed to test comparability among cohorts: calcitriol PO patients were significantly less severe than others (PTH level at baseline lower than 300 pg/ml; p<0.0001); calcitriol IV patients did not reach significant reduction in PTH level. Paricalcitol and paricalcitol+cinacalcet treatment groups results were comparable, while only the IV paricalcitol cohort's PTH level, weekly dosage, and cost decreased significantly from the first to the fourth survey (p=0.020, p=0.012, and p=0.0124, respectively). Total costs per week of treatment (including calcium-based phosphate binder and sevelamer) were significantly lower in the paricalcitol vs paricalcitol+cinacalcet cohort (p<0.001). Major limitations of this study are related to the survey design: not controlled and lack of comparability between cohorts; however, reflective of true practice patterns. CONCLUSIONS: The IV Paricalcitol cohort had significantly lower treatment costs compared with patients treated with paricalcitol+calcimemtics (p<0.001), without a significant difference in terms of baseline severity and PTH control.

Cost-effectiveness of cinacalcet hydrochloride for hemodialysis patients with severe secondary hyperparathyroidism in Japan.

BACKGROUND: Cinacalcet effectively reduces elevated levels of parathyroid hormone (PTH) in patients with secondary hyperparathyroidism (SHPT), even those with severe disease for whom parathyroidectomy can be the treatment of choice. The objective of this study was to estimate the cost-effectiveness of cinacalcet treatment in hemodialysis patients with severe SHPT in Japan. STUDY DESIGN: Cost-effectiveness analysis. SETTING & POPULATION: Patients with severe SHPT (intact PTH >500 pg/mL) who were receiving hemodialysis in Japan. MODEL, PERSPECTIVE, & TIMEFRAME: A Markov model was constructed from the health care system perspective in Japan. Patients were followed up over their lifetime. Dialysis costs were not included in the base case. INTERVENTION: Cinacalcet as an addition to conventional treatment compared to conventional treatment alone. In both arms, patients underwent parathyroidectomy if intact PTH level was >500 pg/mL for 6 months and they were eligible for surgery. OUTCOMES: Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: ICERs for cinacalcet for those who were eligible for surgery and those who were not were $352,631/QALY gained and $21,613/QALY gained, respectively. Sensitivity and scenario analyses showed that results were fairly robust to variations in model parameters and assumptions. In the probabilistic sensitivity analysis, cinacalcet was cost-effective in only 0.9% of simulations for those eligible for surgery, but in more than 99.9% of simulations for those ineligible for surgery, if society would be willing to pay $50,000 per additional QALY. LIMITATIONS: Data for the long-term effect of cinacalcet on patient-level outcomes are limited. The model predicted rates for clinical events using data for the surrogate biochemical end points. CONCLUSIONS: The use of cinacalcet to treat severe SHPT is likely to be cost-effective for only those who cannot undergo parathyroid surgery for medical or personal reasons.

Economic impact of vitamin D treatment on chronic kidney disease patients.

During recent years, increasing recognition has been given to the endocrine action that vitamin D has on the extraskeletal system, and its deep involvement in CKD. This has meant that many vitamin D compounds (both nutritional and active) have been made available, with an important cost reduction. This review looks at the evidence available regarding the usefulness of different types of vitamin D (nutritional and active) for patients with stage 3-5 CKD and those undergoing dialysis. Emphasis is given to its usefulness to control hyperparathyroidism and its impact on morbidity and mortality. We also analysed pharmacoeconomic studies that have been published which compare active vitamin D metabolites. From this review, we are able to conclude that there is still not enough scientific evidence to be able to prefer one active vitamin D over another. In the meantime, doctors should follow the recommendations given in clinical practice guidelines, always taking into account their personal experience with patients. Furthermore, they must consider the economic impact that their treatment decisions may have.

Cinacalcet: a pharmacoeconomic review of its use in secondary hyperparathyroidism in end-stage renal disease.

This article provides an overview of the clinical profile of the calcimimetic agent cinacalcet (Mimpara®, Sensipar®) in the treatment of patients with secondary hyperparathyroidism (SHPT) undergoing dialysis for end-stage renal disease (ESRD), followed by a comprehensive review of pharmacoeconomic analyses with cinacalcet in this patient population. Most patients with ESRD undergoing dialysis develop SHPT, which is associated with disturbances in bone mineral metabolism and the development of fractures, cardiovascular disease and other clinical events. Standard treatment of SHPT includes phosphate binders and active vitamin D derivatives. However, standard treatment alone seldom achieves recommended target plasma or serum levels of parathyroid hormone (PTH), calcium and phosphorous. The addition of cinacalcet to standard therapy in patients with SHPT undergoing dialysis for ESRD improves the likelihood of achieving target biochemical levels compared with standard therapy alone. On the basis of association studies, improvements in these intermediate endpoints are likely to reduce the risk of clinical events, such as fractures and cardiovascular disease. Therefore, part of the acquisition cost of cinacalcet is likely to be offset by reductions in other healthcare resource use, such as reductions in costs associated with a lower likelihood of clinical events, as well as potential reductions in dosages of standard treatment. A number of pharmacoeconomic analyses across various country settings indicate that cinacalcet plus standard therapy is cost effective relative to standard therapy alone if dialysis costs are excluded, or that early initiation of cinacalcet is cost effective compared with delaying cinacalcet treatment until PTH levels become very uncontrolled. However, across analyses with cinacalcet, results were variable and not always favourable. This wide range of results stems from differences in selection of data sources used to populate the models, regional differences in healthcare resource use and costs, as well as other factors. Future cost-effectiveness analyses with cinacalcet should incorporate data on hard clinical outcomes from the EVOLVE study once this information becomes available.

An economic comparison of surgical and medical therapy in patients with secondary hyperparathyroidism--the German perspective.

BACKGROUND: Treatment options for secondary hyperparathyroidism were significantly amended with the introduction of cinacalcet and paricalcitol. Limitations of resources in public health systems demand detailed analyses of accruing costs. The aim of this study was to compare the costs of these new treatment modalities to surgery. METHODS: Patients who underwent initial parathyroidectomy (n = 91) and patients treated with cinacalcet or paricalcitol (n = 100) at an ambulatory dialysis center between 01/2003 and 12/2006 were analyzed. The revenues of both therapies for the funding agencies were calculated by a cost-cost analysis. The real arising costs of the supplier were analyzed and compared to the revenues. RESULTS: Treatment costs for cinacalcet (60 mg/day/year) were 5828.40€ and 4485.20€ for paricalcitol (15 µg/week/year). Revenues for inpatient surgical treatment according to the German DRG system were 3755.38€/case. Additionally, costs for postoperative ambulatory therapies were 545.05€ for the first year and 384.97€ for the following. CONCLUSION: Due to linearly increases, expenses of medical treatment with cinacalcet for more than 9 months or paricalcitol for more than 12 months exceeded the costs of surgical therapy. The indication of these new medical therapies should be restricted to patients as an interim solution ahead of surgery or in patients considered unfit for surgery.

Economic evaluation of cinacalcet in the treatment of secondary hyperparathyroidism in Italy.

BACKGROUND: Imbalanced levels of parathyroid hormone (PTH), serum calcium (Ca) and phosphorous (P) are associated with an increased risk of cardiovascular (CV) death and fracture in dialysis patients with secondary hyperparathyroidism (SHPT). The calcimimetic agent cinacalcet can attenuate the mineral and hormonal imbalances characteristic of SHPT and may improve outcomes in such patients. Here we describe a cost-utility analysis of cinacalcet for SHPT in dialysis patients in Italy. METHODS: We developed a probabilistic Markov model to simulate the effect of cinacalcet on Ca, P and PTH levels in dialysis patients with SHPT, based on data from a European, multicentre, open-label study. The model then correlated these levels with mortality and morbidity (CV events, fractures and parathyroidectomies) using data from the literature, and incorporated Italian data for dialysis, drugs and management of events according to the national cost structure. The simulation horizon was patient lifetime; simulated treatment alternatives were standard treatment (mainly vitamin D sterols and phosphate binders) and cinacalcet + standard treatment. A 3.5% discount rate was applied to life expectancy (LE), quality-adjusted life-expectancy (QALE), costs and times below the upper ranges (time in range [TiR]) recommended by the National Kidney Foundation - Kidney Disease Outcomes Quality initiative for PTH, Ca, P and Ca × P. Utilities were derived from the published literature and took into account dialysis and the impairment of quality of life due to the occurrence of CV events and fractures. Costs were evaluated in year 2009 values from the perspective of the Italian National Healthcare System. RESULTS: Baseline results were calculated with 10,000 iterations. Compared with standard treatment alone, addition of cinacalcet was associated with a mean (SD) increase in TiR of 5.26 (6.59), 3.63 (6.87), 1.70 (6.66) and 2.68 (5.55) discounted patient-years for PTH, Ca and P, respectively, and combined PTH, Ca, P and Ca × P. Cinacalcet increased LE by 1.20 (3.75) life-years (LYs) and QALE by 0.89 (2.59) QALYs. When including the cost for dialysis, the incremental cost-effectiveness ratio (ICER) was €50,012 per LY and €67,361 per QALY, while, if dialysis costs were not included, the ICER was €23,473 per LY and €31,616 per QALY. CONCLUSIONS: The results suggest that cinacalcet treatment could be considered cost effective for treatment of SHPT in the Italian healthcare setting, but further investigations are needed to confirm these findings.