RESUMO
INTRODUCTION: Hyperphosphatemia and hyperparathyroidism are common in end-stage kidney disease and are associated with poor outcomes. In addition to adequate dialysis, medications are usually required for optimum control of serum phosphate and parathyroid hormone (PTH) levels. The use of calcium-based phosphate binders (CBPBs) and active vitamin D is associated with an increase in serum calcium and worsening vascular calcification. To overcome these limitations, non-calcium-based phosphate binders (NCBPBs) and calcimimetics have been developed. However, the coverage for these new medications remains limited in several parts of the world due to the lack of patient-level outcome data and cost. The present study examined the differences in mineral outcomes between two main categories of healthcare programs that provided different coverage for medications used to control mineral and bone disorders (MBD). The Social Security/Universal Coverage (SS/UC) program covered only CBPBs and active vitamin D, whereas the Civil Servant/State Enterprise (CS/SE) program provided coverage of CBPBs, active vitamin D, NCBPBs, and calcimimetics. METHODS: This 10-year retrospective cohort study examined the differences in mineral outcomes between two healthcare programs in maintenance hemodialysis patients. The differences in serum calcium, phosphate, and PTH levels, as well as the aortic arch calcification score, were analyzed according to dialysis vintage by linear mixed-effects regression analyses. The difference in the composite outcome of severe hyperparathyroidism and parathyroidectomy was analyzed by the Cox-proportional hazard regression model. RESULTS: 714 patients were included in the analyses (full cohort). Of these patients, 563 required at least one type of medication to control MBD (MBD medication subgroup). Serum calcium, phosphate, and the proportions of patients with hypercalcemia and hyperphosphatemia were substantially higher in the SS/UC group compared with the CS/SE group after appropriate adjustments for confounders in both the full cohort and the MBD medication subgroup. These findings were confirmed in propensity-score matched analyses. Higher parathyroid hormone levels and a higher rate of the composite endpoint of severe hyperparathyroidism and parathyroidectomy were also observed in the SS/UC group. A more rapid progression of aortic arch calcification was suggested in the SS/UC group, but between-group changes were not significant. CONCLUSION: Patients under the healthcare program that did not cover the use of NCBPBs and calcimimetics showed higher serum calcium and phosphate levels and a more rapid progression of hyperparathyroidism. The difference in the progression of vascular calcification could not be confirmed in the present study.
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Calcimiméticos , Cálcio , Hiperfosfatemia , Fosfatos , Diálise Renal , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Calcimiméticos/uso terapêutico , Hiperfosfatemia/etiologia , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/sangue , Cálcio/sangue , Idoso , Fosfatos/sangue , Falência Renal Crônica/terapia , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Hormônio Paratireóideo/sangue , Vitamina D/sangue , Quelantes/uso terapêuticoRESUMO
Hyperphosphatemia is an electrolyte disorder highly prevalent in patients with chronic kidney disease undergoing hemodialysis (HD) that usually requires treatment with oral phosphate binders (PBs). Sucroferric oxyhydroxide (SO) is a calcium-free, iron-based PB indicated for the control of serum phosphorus. In the real-world setting, SO has shown clinical effectiveness with a lower pill burden and has also been associated with reduced hospital admission rates. This study aims to assess the potential economic benefits resulting from the introduction of SO to the health-care setting of the Kingdom of Saudi Arabia (KSA). An economic analysis using data from a retrospective real-world study that compared HD patients with uninterrupted SO prescriptions with patients who discontinued SO and switched to other PBs (oPBs). Annual drug costs for the estimated PB-eligible population in KSA were quantified. Costs per responder were estimated for all treatments. Hospital admissions' incidence rates were converted into annual inpatient cost savings and were deducted from drug costs to estimate the annual economic effect of SO versus oPBs. Sensitivity and breakeven analyses were also conducted. The eligible population for PB therapy in KSA was estimated at n = 14,748. Treating therapy-eligible populations exclusively with SO was estimated to generate annual inpatient cost-savings of SAR 107.4-119.4 million compared to treating the population with oPBs. The estimated economic effect signified overall annual savings ranging from SAR 82.8 to SAR 94.8 million when the population is treated with SO. Sensitivity analyses showed persistent cost savings. The estimated benefit-cost ratios showed that for every SAR 1 spent on SO, the expected return on investment was SAR 4.4-4.9. SO is an effective therapy that may result in substantial cost savings from reducing hospital admission costs that are attributable to hyperphosphatemia among HD patients.
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Hiperfosfatemia , Insuficiência Renal Crônica , Humanos , Diálise Renal/efeitos adversos , Hiperfosfatemia/diagnóstico , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Estudos Retrospectivos , Arábia Saudita , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapiaRESUMO
INTRODUCTION: For patients with chronic kidney disease (CKD), the need for phosphate binder (PB) treatment peaks at onset of dialysis. This real-world study assessed rates of PB utilization and switching in patients with dialysis-dependent CKD (DD-CKD). METHODS: We identified patients with PB utilization among those with prevalent DD-CKD using 2018-2019 Medicare Parts A/B/D data. Patients were assigned to cohorts based on primary (most frequently used) PB among calcium acetate, ferric citrate, lanthanum carbonate, sevelamer (hydrochloride and carbonate), sucroferric oxyhydroxide. We measured proportion of patients who were adherent (proportion of days covered >80%) and persistent (patients whose last 90 days of outpatient dialysis reported PB use). Net switching rates were calculated as the difference between switches to and from the primary agent. RESULTS: We identified 136,912 patients with PB use. Proportion of patients adherent ranged from 63.8% (lanthanum carbonate) to 67.7% (sevelamer) and persistent from 85.1% (calcium acetate) to 89.5% (ferric citrate). Most patients (73%) used the same PB throughout the study. Overall, 20.5% of patients experienced one switch and 2.3% two or more. Positive net switching rates were observed for ferric citrate, sucroferric oxyhydroxide, and lanthanum carbonate (2-10%) but negative for sevelamer and calcium acetate (-2% to -7%). CONCLUSION: Adherence and persistence rates were low with slight variation across PBs. Net positive switching occurred for ferric citrate, sucroferric oxyhydroxide, and lanthanum carbonate. Further studies are needed to determine the reasons for these findings and could identify opportunities for better control of phosphate levels among patients with CKD.
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Hiperfosfatemia , Insuficiência Renal Crônica , Estados Unidos , Humanos , Idoso , Sevelamer/uso terapêutico , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Diálise Renal/efeitos adversos , Medicare , Compostos Férricos/uso terapêutico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Fosfatos , Quelantes/uso terapêuticoRESUMO
CONTEXTO: A doença renal crônica (DRC) é um problema de saúde pública crescente em todo o mundo, acompanhada de comorbidades muitas vezes mais graves do que a própria perda da função renal. Dentre elas, destacam-se os distúrbios do metabolismo ósseo e mineral (DMO), que levam à doença óssea e cardiovascular. Dessa forma, o DMO-DRC, além de poder resultar em fraturas, dor, deformidades ósseas e menor velocidade de crescimento nas crianças, também é fator de risco para calcificação vascular e associa-se a miocardiopatia e hipertrofia do ventrículo esquerdo, com consequente aumento do risco para doença cardíaca isquêmica, insuficiência cardíaca e morte de causa cardiovascular. Os mecanismos comuns entre a doença óssea e cardiovascular se apoiam nas crescentes evidências de que alterações na remodelação óssea favorecem o desenvolvimento de calcificações extra ósseas, principalmente vasculares. As alterações no metabolismo mineral e ósseo são frequentes na DRC, observadas já nos estágios iniciais da DRC, quando a taxa de filtração glomerular está em
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Humanos , Insuficiência Renal Crônica/fisiopatologia , Hiperfosfatemia/tratamento farmacológico , Sevelamer/uso terapêutico , Sistema Único de Saúde , Brasil , Análise Custo-BenefícioRESUMO
AIMS: Hyperphosphatemia is common among patients with advanced chronic kidney disease (CKD) undergoing dialysis. The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SO), has a low daily pill burden and is indicated for the control of serum phosphorus in these patients. In a retrospective database study, hemodialysis patients switched to long-term SO therapy had fewer hospitalizations compared with patients switched to other PB therapies. This economic analysis aimed to quantify potential cost-savings of reduced hospitalizations associated with SO for healthcare systems in five European countries. MATERIALS AND METHODS: All-cause hospital admissions incidence data were sourced from a real-world retrospective database study comparing adult, in-center hemodialysis patients maintained on 2 years of SO therapy (mSO) versus patients who discontinued SO (dSO) within 90 days of their first prescription and switched to other PBs. A literature search was conducted to determine the cost per hospital admission for dialysis patients in the healthcare setting of each European country. A cost-model combined the incidence rate of all-cause hospital admissions and the cost per admission to estimate the country-specific inpatient costs for the mSO and dSO groups. RESULTS: Annual inpatient cost-savings per patient in the mSO group versus the dSO group were 1,201, 2,097, 2,059, 1,512, and 3,068 in France, Germany, Italy, Spain, and the UK, respectively. When annual PB drug costs per patient were considered, the net annual economic cost-savings per patient were 327, 1,585, 1,022, 1,100, and 2,204, respectively. LIMITATIONS: Hospital admissions data used in the analysis were observational in nature and derived from a US hemodialysis patient population; the effect of SO therapy on hospitalization rates for US and European hemodialysis patients may differ. The analysis did not consider indirect healthcare costs associated with hospitalizations. CONCLUSION: SO therapy may offer substantial inpatient cost-savings by reducing all-cause hospital admissions attributable to uncontrolled hyperphosphatemia.
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Hiperfosfatemia , Pacientes Internados , Adulto , Redução de Custos , Combinação de Medicamentos , Compostos Férricos , Hospitais , Humanos , Hiperfosfatemia/tratamento farmacológico , Diálise Renal , Estudos Retrospectivos , SacaroseRESUMO
Currently, various hyperphosphatemia drugs are administered orally to hemodialysis patients in order to lower serum phosphorus levels. However, it is known that medication adherence is poor, possibly due to greater pill burden taken each time and their complicated schedules. Therefore, large amounts of unused hyperphosphatemia drugs are likely to be leftover. The increase in leftover prescribed drugs leads to the unnecessary elevation of medical care costs. To date, however, the available information on leftover hyperphosphatemia drugs in hemodialysis outpatients is limited. In this study, we performed an interview survey of medication adherence to hyperphosphatemia drugs among 60 hemodialysis outpatients and evaluated the cost of the leftover drugs. Thirty-four patients showed good adherence. On the other hand, 19 patients self-adjusted to take hyperphosphatemia drugs according to their daily diet. When assessing the serum phosphorus levels for these patients over the past year, the values often exceeded the targeted range (3.5-6.0 mg/mL). Furthermore, 35 patients kept hyperphosphatemia drugs at their home. When estimating the cost derived from leftover drugs using the bootstrap method, main distribution of drug cost was shown to be in the range of 2000 to 2500 yen. This drug cost seemed to in part reflect preparation for an emergency. A serious problem was that 14 patients had previous experience in discarding hyperphosphatemia drugs. This study suggested that more appropriate pharmaceutical care according to each patient's situation is essential in improving phosphorus control in hemodialysis outpatients and in reducing the waste of medical resources.
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Custos de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/economia , Custos de Cuidados de Saúde , Recursos em Saúde/economia , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/economia , Adesão à Medicação/estatística & dados numéricos , Pacientes Ambulatoriais/psicologia , Prescrições/economia , Prescrições/estatística & dados numéricos , Diálise Renal/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hiperfosfatemia/etiologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Uncontrolled hyperphosphatemia in chronic kidney disease (CKD) patients commonly results in vascular calcification leading to increased risk of cardiovascular disease. Phosphate binders (PBs) are used for hyperphosphatemia and can be calcium-based (CBPBs) or non-calcium-based (NCBPBs), the latter being more expensive than CBPBs. In this study, we used meta-analysis approaches to assess the cost-utility of PBs for hyperphosphatemia in CKD patients. METHODS: Relevant studies published prior to June 2019 were identified from PubMed, Scopus, the Cochrane Library, the National Health Service Economic Evaluation Database, and the Cost-Effectiveness Analysis Registry. Studies were eligible if they included CKD patients with hyperphosphatemia, compared any PBs and reported economic outcomes. Meta-analysis was applied to pool incremental net benefit (INB) across studies stratified by country income. RESULTS: A total of 25 studies encompassing 32 comparisons were eligible. Lanthanum carbonate, a NCBPB, was a more cost-effective option than CBPBs in high-income countries (HICs), with a pooled INB of $3984.4 (599.5-7369.4), especially in pre-dialysis patients and used as a second-line option with INBs of $4860.2 (641.5-9078.8), $4011.0 (533.7-7488.3), respectively. Sevelamer, also a NCBPB, was not more cost-effective as a first-line option compared to CBPBs with a pooled INB of $6045.8 (- 23,453.0 to 35,522.6) and $34,168.9 (- 638.0 to 68,975.7) in HICs and upper middle-income countries, respectively. CONCLUSIONS: Lanthanum carbonate was significantly more cost-effective than CBPBs as a second-line option for hyperphosphatemia in pre-dialysis patients in HICs. However, the use of sevelamer is not more cost-effective as a first-line option compared to CBPBs.
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Hiperfosfatemia , Insuficiência Renal Crônica , Análise Custo-Benefício , Humanos , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Fosfatos , Diálise Renal , Insuficiência Renal Crônica/complicações , Medicina EstatalRESUMO
OBJECTIVES: Lanthanum (La) retention in bone has been shown to occur in individuals who are orally administered lanthanum carbonate (LaC), a drug to treat hyperphosphatemia. The breakdown of LaC in the gastrointestinal tract into La3+ and carbonate ions results in residual quantities of La being deposited in bone. We previously reported on a non-invasive x-ray fluorescence (XRF) system that was developed to quantify bone La concentrations and applied it to a series of excised cadaver tibiae. However, given interpatient variability in bone shape and size, differential signal attenuation that occurs in bone and tissue, patient movement and overlying tissue thickness at the measurement site, quantifying bone La concentrations during in vivo measurements in live subjects needs to be investigated further along with the radiation dose associated with the measurement. APPROACH: Coherent normalization was investigated as a function of overlying tissue thickness, source-subject distance and bone radius through Monte Carlo simulation and experimental work. This was accomplished by observing the ratio of the net La K x-ray peak area to the coherently scattered peak area at 59.5 keV. In addition, the dose delivered during a 2000 s measurement was determined using radiochromic film. MAIN RESULTS: The coherent normalization of the La x-ray signal was shown to be independent of overlying tissue thickness, source-subject movement and bone radius, which indicates that this normalization procedure can correct for these factors. The equivalent skin dose and effective dose were 18.0 mSv and 3.2 µSv, respectively for a five-year-old. SIGNIFICANCE: While coherent normalization for the bone lead (Pb) and bone gadolinium (Gd) systems has been shown to be successful, we also report that this normalization procedure can correct for these interpatient variabilities in the in vivo 241Am-La K XRF system.
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Osso e Ossos/diagnóstico por imagem , Lantânio , Pré-Escolar , Fluorescência , Humanos , Hiperfosfatemia/tratamento farmacológico , Lantânio/análise , Método de Monte Carlo , Imagens de Fantasmas , Doses de Radiação , Espectrometria por Raios X , Raios XRESUMO
OBJECTIVE: Non-calcium containing phosphate binders (non-CPBs) are useful for the treatment of hyperphosphatemia without a concern of hypercalcemia in patients undergoing dialysis. However, due to their relatively high cost, prescribing non-CPBs is restricted in South Korea. This study was conducted to investigate prescribing patterns, especially switching between CPBs and non-CPBs, in dialysis patients in a real-world setting. MATERIALS AND METHODS: This is an observational study using the National Health Insurance Service claim data. The study population included patients who initiated dialysis between July 2012 and June 2013 and were prescribed phosphate binders at least once during the observation period (2012 - 2016) (n = 10,073). Medication costs and prescribing patterns including switching of phosphate binders were investigated. RESULTS: Compared with the first year of dialysis, the costs of phosphate binders more than doubled during the 4th year of dialysis (from US$ 28.4 to US$ 60.1), largely due to an increase in the cost of non-CPBs (from US$ 117.5 to US$ 237.8). Many patients continued to change drugs between CPBs and non-CPBs. The continuous prescription period of CPBs was shortened each time a drug was changed. A total of 551 patients (13.4%) changed their medication three times between CPBs and non-CPBs. CONCLUSION: Over time on dialysis, use of non-CPB increased and medication costs increased accordingly. Many patients continued to change drugs between CPBs and non-CPBs due to the restricted criteria of the health insurance. Further outcome research is necessary to evaluate the appropriateness of the clinical practice in which CPBs and non-CPBs are alternately used.
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Quelantes/administração & dosagem , Substituição de Medicamentos/economia , Hiperfosfatemia/tratamento farmacológico , Padrões de Prática Médica/tendências , Diálise Renal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quelantes/economia , Criança , Pré-Escolar , Custos de Medicamentos , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fosfatos/antagonistas & inibidores , República da Coreia , Adulto JovemRESUMO
INTRODUCTION: End-stage renal disease is associated with significant comorbidity and mortality. Among its implications, hyperphosphatemia constitutes a consistent and independent risk factor. The use of benchmark treatment, low-cost calcium-based binders declined due to a potential calcification effect on coronary arteries. AREAS COVERED: Given the increasing prevalence of end-stage renal disease and the high cost of hyperphosphatemia's new primary modality, the non-calcium based phosphate binders, we set-off to systematically assess the economic evaluations of non-calcium containing phosphate binders, sevelamer and lanthanum. The study was performed based on a systematic review of the economic evaluations of sevelamer and lanthanum. The cost-effectiveness profile of the two non-calcium-containing Phosphate Binders compared to calcium-based phosphate binders depends on several factors such as future dialysis costs, utility values, age, survival, and phosphorus levels. EXPERT OPINION: The comparison between the two agents is rather inconclusive; nevertheless, current review suggests that non-calcium-based phosphate binders may yield a positive cost-effectiveness ratio in patients with inadequate phosphorus management and patient with longer life-expectancy. It is crucial that the literature is endowed with more data, specifically on survival, future dialysis costs, and calcification.
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Hiperfosfatemia/tratamento farmacológico , Lantânio/administração & dosagem , Sevelamer/administração & dosagem , Quelantes/administração & dosagem , Quelantes/economia , Análise Custo-Benefício , Humanos , Hiperfosfatemia/economia , Falência Renal Crônica/economia , Falência Renal Crônica/terapia , Lantânio/economia , Expectativa de Vida , Diálise Renal/economia , Sevelamer/economiaRESUMO
BACKGROUND: Phosphate binders are used to treat hyperphosphatemia among patients with chronic kidney disease (CKD). OBJECTIVES: To conduct an economic evaluation comparing calcium-free binders sevelamer and lanthanum with calcium-based binders for patients with CKD. METHODS: Effectiveness data were obtained from a recent meta-analysis of randomized trials. Effectiveness was measured as life-years gained and translated to quality-adjusted life-years (QALYs) using utility weights from the literature. A Markov model consisting of non-dialysis-dependent (NDD)-CKD, dialysis-dependent (DD)-CKD, and death was developed to estimate the incremental costs and effects of sevelamer and lanthanum versus those of calcium-based binders. A lifetime horizon was used and both costs and effects were discounted at 1.5%. All costs are presented in 2015 Canadian dollars from the Canadian public payer perspective. Results of probabilistic sensitivity analysis were presented using cost-effectiveness acceptability curves. Sensitivity analyses were conducted for risk pooling methods, omission of dialysis costs, and persistence of drug effects on mortality. RESULTS: Sevelamer resulted in an incremental cost-effectiveness ratio of $106,522/QALY for NDD-CKD and $133,847/QALY for DD-CKD cohorts. Excluding dialysis costs, sevelamer was cost-effective in the NDD-CKD cohort ($5,847/QALY) and the DD-CKD cohort ($11,178/QALY). Lanthanum was dominated regardless of whether dialysis costs were included. CONCLUSIONS: Existing evidence does not clearly support the cost-effectiveness of non-calcium-containing phosphate binders (sevelamer and lanthanum) relative to calcium-containing phosphate binders in DD-CKD patients. Our study suggests that sevelamer may be cost-effective before dialysis onset. Because of the remaining uncertainty in several clinically relevant outcomes over time in DD-CKD and NDD-CKD patients, further research is encouraged.
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Carbonato de Cálcio/economia , Análise Custo-Benefício/métodos , Hiperfosfatemia/economia , Lantânio/economia , Insuficiência Renal Crônica/economia , Sevelamer/economia , Adulto , Idoso , Carbonato de Cálcio/administração & dosagem , Quelantes/administração & dosagem , Quelantes/economia , Feminino , Humanos , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/epidemiologia , Lantânio/administração & dosagem , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto/economia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Sevelamer/administração & dosagemRESUMO
Medicare costs for phosphate binders for US dialysis patients and patients with chronic kidney disease enrolled in Medicare Part D exceeded $1.5 billion in 2015. Previous data have shown that Part D costs for mineral and bone disorder medications increased faster than costs for all Part D medications for dialysis patients. Despite extensive use of phosphate binders and escalating costs, conclusive evidence is lacking that they improve important clinical end points in dialysis patients or non-dialysis-dependent patients with chronic kidney disease. Using dialysis patient data from the US Renal Data System and laboratory information from the Centers for Medicare & Medicaid Services (CMS) CROWNWeb data, we update information on trends in phosphate-binder use, calcium and phosphorus values, and costs for Medicare-covered dialysis patients. We discuss these results in the context of evidence from clinical trials, meta-analyses, and observational studies evaluating phosphate-binder efficacy, safety, comparative effectiveness, and cost-effectiveness. Based on our analysis, we note a need for US Food and Drug Administration guidance regarding clinical evaluation of new phosphate binders, and we suggest that it would be in CMS' best interest to fund a clinical trial to assess whether lower versus higher phosphate concentrations improve hard clinical outcomes, and if so, whether particular phosphate binders are superior to placebo or other binders in improving these outcomes.
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Hiperfosfatemia/tratamento farmacológico , Falência Renal Crônica , Lantânio , Diálise Renal , Sevelamer , Cálcio/sangue , Quelantes/economia , Quelantes/uso terapêutico , Controle de Medicamentos e Entorpecentes/métodos , Controle de Medicamentos e Entorpecentes/organização & administração , Custos de Cuidados de Saúde , Humanos , Hiperfosfatemia/etiologia , Falência Renal Crônica/sangue , Falência Renal Crônica/economia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Lantânio/economia , Lantânio/uso terapêutico , Medicare Part D , Avaliação das Necessidades , Fósforo/sangue , Diálise Renal/economia , Diálise Renal/métodos , Diálise Renal/estatística & dados numéricos , Sevelamer/economia , Sevelamer/uso terapêutico , Estados Unidos/epidemiologiaRESUMO
As kidney disease progresses, phosphorus retention also increases, and phosphate binders are used to treat hyperphosphatemia. Clinicians prescribe phosphate binders thinking that reducing total body burden of phosphorus may decrease risks of mineral and bone disorder, fractures, cardiovascular disease, progression of kidney disease, and mortality. Recent meta-analyses suggest that sevelamer use results in lower mortality than use of calcium-containing phosphate binders. However, studies included in meta-analyses show significant heterogeneity, and exclusion or inclusion of specific studies alters results. Since no long-term studies have been conducted to determine whether treatment with any phosphate binder is better than placebo on any hard clinical endpoint (including mortality), it is unclear whether possible benefit with sevelamer represents net benefit of sevelamer, net harm with calcium-containing phosphate binders, or both. Although one meta-analysis suggested that calcium acetate may be more efficacious gram for gram than calcium carbonate as a binder, calcium acetate did not reduce hypercalcemia, and gastrointestinal intolerance was higher. Data are insufficient to determine whether calcium acetate provides lower risk of vascular calcification than calcium carbonate. Fears of lanthanum accumulation in the central nervous system or bone with long-term treatment do not appear to be warranted. Newer iron-containing phosphate binders have potential benefits, such as lower pill burden (sucroferric oxyhydroxide) and improved iron parameters (ferric citrate). The biggest challenge to phosphate binder efficacy is non-adherence. This article reviews the current knowledge regarding safety, effectiveness, and adherence with currently marketed phosphate binders and those in development.
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Quelantes/uso terapêutico , Hiperfosfatemia/tratamento farmacológico , Lantânio/uso terapêutico , Fosfatos/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Compostos de Cálcio/efeitos adversos , Compostos de Cálcio/metabolismo , Compostos de Cálcio/uso terapêutico , Quelantes/efeitos adversos , Quelantes/economia , Quelantes/farmacologia , Custos de Medicamentos , Compostos Férricos/efeitos adversos , Compostos Férricos/metabolismo , Compostos Férricos/uso terapêutico , Humanos , Hiperfosfatemia/etiologia , Lantânio/metabolismo , Lantânio/farmacologia , Metanálise como Assunto , Fosfatos/sangue , Insuficiência Renal Crônica/complicações , Sevelamer/uso terapêuticoRESUMO
OBJECTIVE: The objective of this article was to assess the safety and efficacy of long-term administration of PA21. DESIGN AND METHODS: Phase III, open-label, long-term study in 15 sites in Japan. SUBJECTS: Japanese hemodialysis patients (N = 161) with hyperphosphatemia aged ≥20 years undergoing stable maintenance hemodialysis 3 times weekly, for ≥12 weeks. INTERVENTION: After a 2-week observation period with their previous hyperphosphatemia therapy, patients began the 52-week treatment with PA21, which was administered orally at an initial dose of 250 mg, 3 times daily, immediately before every meal (dosing range between 750 and 3,000 mg/day). MAIN OUTCOME MEASURE: Safety was evaluated based on the development of adverse events and adverse drug reactions (ADRs). Efficacy was evaluated according to serum phosphorus concentration, corrected serum calcium concentration, and serum intact-parathyroid hormone concentration. RESULTS: The mean serum phosphorus concentration decreased from 5.46 ± 1.06 mg/dL at baseline to 5.00 ± 1.17 mg/dL at end of treatment. The serum phosphorus concentration was maintained within the target range (3.5-6.0 mg/dL) throughout the 52 weeks of the study period with a mean of 3.3 tablets per day of PA21. Most ADRs were mild, transient, and developed early during treatment, and the incidence was not shown to increase with long-term treatment. The most frequently reported ADR was diarrhea (22.4%). CONCLUSION: Treatment with PA21 was effective in lowering and maintaining target serum phosphorus concentrations in Japanese hemodialysis patients with hyperphosphatemia over 52 weeks. PA21 was generally well tolerated in the long term.
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Compostos Férricos/uso terapêutico , Hiperfosfatemia/sangue , Hiperfosfatemia/tratamento farmacológico , Diálise Renal , Sacarose/uso terapêutico , Idoso , Povo Asiático , Combinação de Medicamentos , Feminino , Humanos , Japão , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fósforo/sangue , Resultado do TratamentoRESUMO
Ferric citrate (FC) has demonstrated efficacy as a phosphate binder and reduces the requirements for erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron in dialysis patients. We developed a net budgetary impact model to evaluate FC vs. other phosphate binders from the vantage of a large dialysis provider. We used a Markov microsimulation model to simulate mutually referential longitudinal effects between serum phosphate and phosphate binder dose; categories of these defined health states. Health states probabilistically determined treatment attendance and utilization of ESA and IV iron. We derived model inputs from a retrospective analysis of incident phosphate binder users from a large dialysis organization (January 2011-June 2013) and incorporated treatment effects of FC from a phase III trial. The model was run over a 1-year time horizon. We considered fixed costs of providing dialysis; costs of administering ESA and IV iron; and payment rates for dialysis, ESAs, and IV iron. In the base-case model, FC had a net budgetary impact (savings) of +US$213,223/year per 100 patients treated vs. standard of care. One-way sensitivity analyses showed a net budgetary impact of up to +US$316,296/year per 100 patients treated when higher hemoglobin levels observed with FC translated into a 30% additional ESA dose reduction, and up to +US$223,281/year per 100 patients treated when effects on missed treatment rates were varied. Two-way sensitivity analyses in which acquisition costs for ESA and IV iron were varied showed a net budgetary impact of +US$104,840 to +US$213,223/year per 100 patients treated. FC as a first-line phosphate binder would likely yield substantive savings vs. standard of care under current reimbursement.
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Compostos Férricos/economia , Compostos Férricos/uso terapêutico , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/economia , Cadeias de Markov , Fosfatos/sangue , Relação Dose-Resposta a Droga , Compostos Férricos/administração & dosagem , Hematínicos/administração & dosagem , Hematínicos/economia , Hematínicos/uso terapêutico , Humanos , Hiperfosfatemia/sangue , Estudos RetrospectivosRESUMO
PURPOSE: To conduct a cost-effectiveness analysis study of sevelamer versus calcium-based binders (CBBs) in treating hyperphosphatemia among patients with end-stage renal disease (ESRD) in China. METHODS: A decision-analytic model of a lifetime horizon was used for base case analysis from the payers' perspective. The transition probabilities between different health states were derived from survival analysis. The overall survival of CBBs was derived from the Dialysis Clinical Outcomes Revisited study for up to 44 months and a Weibull regression model was used to extrapolate the overall survival to a lifetime horizon. A hazard ratio (0.54; 95% CI, 0.32-0.93) of the overall survival for sevelamer versus CBBs was used to calculate the survival of the sevelamer group. Clinical and cost data were derived from literature and health care system in the local setting. Incremental life year and quality-adjusted life year (QALY) were the primary outcomes. One-way and probabilistic sensitivity analyses were conducted to assess the uncertainty of the model assumptions and parameters. The results were reported in 2015 Chinese Renminbi. FINDINGS: The incremental cost per life year and per QALY gained of sevelamer versus CBBs was ¥44,475 and ¥57,910, respectively. The incremental cost per QALY gained was below the World Health Organization's recommended cost-effectiveness threshold (¥151,070), which is 3 times the gross domestic product per capita of 2015 in China. The incremental cost-effectiveness ratio was most sensitive to the hazard ratio of overall survival with sevelamer versus CBBs in the 1-way sensitivity analysis. The cost-effectiveness acceptability curve indicated that sevelamer had a 89.6% likelihood of cost-effectiveness at the ¥151,070 threshold. IMPLICATIONS: Sevelamer is likely to be a cost-effective option in treating hyperphosphatemia among patients with ESRD compared with CBBs in the local context of China.
Assuntos
Cálcio/uso terapêutico , Hiperfosfatemia/tratamento farmacológico , Falência Renal Crônica/terapia , Sevelamer/uso terapêutico , Quelantes/uso terapêutico , China , Análise Custo-Benefício , Humanos , Masculino , Anos de Vida Ajustados por Qualidade de Vida , Análise de SobrevidaRESUMO
Hyperphosphatemia management is integral to the management of patients with chronic kidney disease. This mineral abnormality is associated with greater costs, but so is its management, especially with the use novel phosphate binders. The economic evaluation of these pharmaceutical agents is increasingly needed to provide evidence for value of money spent and inform resource allocation. Recently, Nguyen et al. explored the economical attractiveness of Sevelamer relative to Calcium Carbonate among patients with chronic kidney disease not yet on dialysis and concluded that the former was cost-effective. The current commentary discusses the results of this analysis and sheds light on the methodological challenges of economic evaluations in this field.
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Quelantes/economia , Quelantes/uso terapêutico , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/economia , Carbonato de Cálcio/economia , Carbonato de Cálcio/uso terapêutico , Análise Custo-Benefício , Humanos , Hiperfosfatemia/etiologia , Insuficiência Renal Crônica/complicações , Sevelamer/economia , Sevelamer/uso terapêuticoRESUMO
BACKGROUND: Sevelamer is an alternative to calcium carbonate for the treatment of hyperphosphatemia among non-dialysis dependent patients with chronic kidney disease (CKD). Although some studies show that it may reduce mortality and delay the onset of dialysis when compared to calcium carbonate, it is also significantly more expensive. Prior studies looking at the incremental cost-effectiveness of sevelamer versus calcium carbonate in pre-dialysis patients are based on data from a single clinical trial. The goal of our study is to use a wider range of clinical data to achieve a more contemporary and robust cost-effectiveness analysis. METHODS: We used a Markov model to estimate the lifetime costs and quality-adjusted life years (QALYs) gained for treatment with sevelamer versus calcium carbonate. The model simulated transitions among three health states (CKD not requiring dialysis, end-stage renal disease, and death). Data on transition probabilities and utilities were obtained from the published literature. Costs were calculated from a third party payer perspective and included medication, hospitalization, and dialysis. Sensitivity analyses were also run to encompass a wide range of assumptions about the dose, costs, and effectiveness of sevelamer. RESULTS: Over a lifetime, the average cost per patient treated with sevelamer is S$180,724. The estimated cost for patients treated with calcium carbonate is S$152,988. A patient treated with sevelamer gains, on average, 6.34 QALYs relative to no treatment, whereas a patient taking calcium carbonate gains 5.81 QALYs. Therefore, sevelamer produces an incremental cost-effectiveness ratio (ICER) of S$51,756 per QALY gained relative to calcium carbonate. CONCLUSION: Based on established benchmarks for cost-effectiveness, sevelamer is cost effective relative to calcium carbonate for the treatment of hyperphosphatemia among patients with chronic kidney disease initially not on dialysis.
Assuntos
Carbonato de Cálcio/economia , Análise Custo-Benefício/métodos , Hiperfosfatemia/economia , Diálise Renal/economia , Insuficiência Renal Crônica/economia , Sevelamer/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiácidos/economia , Antiácidos/uso terapêutico , Carbonato de Cálcio/uso terapêutico , Quelantes/economia , Quelantes/uso terapêutico , Feminino , Humanos , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/epidemiologia , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Sevelamer/uso terapêutico , Singapura/epidemiologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Hyperphosphataemia is common and harmful in patients receiving dialysis. Treatment options include noncalcium-based phosphate binders such as sevelamer carbonate (SC) and sucroferric oxyhydroxide (PA21). OBJECTIVE: The aim of this study was to determine the health economic impact of PA21-based strategies compared with SC-based strategies, from the perspective of the Scottish National Health Service (NHS). METHODS: A Markov model was constructed based on data from a randomised clinical trial comparing PA21 and SC. Model input parameters were derived from published literature, national statistics and unpublished sources. Costs (price year 2012) and effects were discounted at 3.5 %. Analysis with a lifelong time horizon yielded the incremental cost-effectiveness ratio (ICER), expressed as cost or savings per quality-adjusted life-year (QALY) gained or forgone. Deterministic and probabilistic sensitivity analysis was performed to explore uncertainties around assumptions and model input parameters. RESULTS: In the base-case analysis, phosphorus reductions for PA21 and SC were 1.93 and 1.95 mg/dL. Average undiscounted survival was estimated to be 7.61 years per patient in both strategies. PA21 patients accrued less QALYs (2.826) than SC patients (2.835), partially due to differential occurrence of side effects. Total costs were £ 13,119 and £ 14,728 for PA21 and SC, respectively (difference per patient of £ 1609). By using PA21 versus SC, one would save £ 174,999 (or £ 123,463 when including dialysis and transplantation costs) for one QALY forgone. A scenario modelling the nonsignificant reduction in mortality (relative risk 0.714) observed in the trial yielded an ICER for PA21 of £ 22,621 per QALY gained. In probabilistic sensitivity analysis of the base-case, PA21 was dominant in 11 %, and at least cost-effective in 53 %, of iterations, using a threshold of £ 20,000 per QALY gained. CONCLUSIONS: The use of PA21 versus SC in hyperphosphataemic patients being intolerant of calcium-based phosphate binders may be cost saving and yields only very limited disadvantages in terms of quality-adjusted survival. PA21 appears to be cost-effective from the perspective of the Scottish NHS.
Assuntos
Compostos Férricos/economia , Hiperfosfatemia/economia , Modelos Econômicos , Programas Nacionais de Saúde/economia , Diálise Renal , Sevelamer/economia , Sacarose/economia , Análise Custo-Benefício , Combinação de Medicamentos , Compostos Férricos/administração & dosagem , Compostos Férricos/uso terapêutico , Humanos , Hiperfosfatemia/tratamento farmacológico , Cadeias de Markov , Anos de Vida Ajustados por Qualidade de Vida , Escócia , Sevelamer/administração & dosagem , Sevelamer/uso terapêutico , Sacarose/administração & dosagem , Sacarose/uso terapêuticoRESUMO
BACKGROUND: The recent multicenter, randomized, open-label INDEPENDENT study demonstrated that sevelamer improves survival in new to hemodialysis (HD) patients compared with calcium carbonate. The objective of this study was to determine the cost-effectiveness of sevelamer versus calcium carbonate for patients new to HD, using patient-level data from the INDEPENDENT study. STUDY DESIGN: Cost-effectiveness analysis. SETTING AND POPULATION: Adult patients new to HD in Italy. MODEL, PERSPECTIVE, TIMEFRAME: A patient-level cost-effectiveness analysis was conducted from the perspective of the Servizio Sanitario Nazionale, Italy's national health service. The analysis was conducted for a 3-year time horizon. The cost of dialysis was excluded from the base case analysis. INTERVENTION: Sevelamer was compared to calcium carbonate. OUTCOMES: Total life years (LYs), total costs, and the incremental cost per LY gained were calculated. Bootstrapping was used to estimate confidence intervals around LYs, costs, and cost-effectiveness and to calculate the cost-effectiveness acceptability curve. RESULTS: Sevelamer was associated with a gain of 0.26 in LYs compared to calcium carbonate, over the 3-year time horizon. Total drug costs were 3,282 higher for sevelamer versus calcium carbonate, while total hospitalization costs were 2,020 lower for sevelamer versus calcium carbonate. The total incremental cost of sevelamer versus calcium carbonate was 1,262, resulting in a cost per LY gained of 4,897. The bootstrap analysis demonstrated that sevelamer was cost effective compared with calcium carbonate in 99.4 % of 10,000 bootstrap replicates, assuming a willingness-to-pay threshold of 20,000 per LY gained. LIMITATIONS: Data on hospitalizations was taken from a post hoc retrospective chart review of the patients included in the INDEPENDENT study. Patient quality of life or health utility was not included in the analysis. CONCLUSIONS: Sevelamer is a cost-effective alternative to calcium carbonate for the first-line treatment of hyperphosphatemia in new to HD patients in Italy.