RESUMEN
BACKGROUND: Hemoglobin disorders such as thalassemia major have created an economic burden on the health care system. Iron chelation therapy (ICT) is the most expensive cost component in patients with thalassemia. ICT was administered to reduce the toxic effects of iron overload. This study aims to compare the costs of iron chelators as monotherapy in patients with thalassemia major in Indonesia, specifically in Cipto Faculty of Medicine, Universit. METHODS: This is a retrospective analytical observational study. Data were collected from the thalassemia registry from 2016 to 2019. Patients' age, gender, type of thalassemia, and type of iron chelation were recorded. Complications and total annual costs were evaluated. All thalassemia patients aged ≥2 years who were only receiving monotherapy ICT and had no history of therapy switching were eligible. We excluded subjects who moved out to other facilities or lost to follow-up. RESULTS: From a total of 256 subjects, 249 subjects were included. The median age is 28 years old. Both sexes were represented equally. As many as 96.8% of subjects have thalassemia beta. Deferiprone was the most common iron chelator used (86.7%). Complications were observed in the subjects based on 4-year data collection; most of them were cardiomyopathy, diabetes mellitus, delayed puberty, and malnutrition ( P =0.422; P =0.867; P =0.004; and P =0.125, respectively). Deferiprone had a lower mean annual cost of USD 3581 than deferasirox, which had a cost of USD 6004. CONCLUSIONS: Cardiomyopathy, diabetes mellitus, delayed puberty, and malnutrition were the most common complications found in the study. This study showed that deferiprone should be taken as consideration as a drug of choice to treat iron overload in thalassemia provided by Indonesian national health insurance which is less costly despite the probability of complications found after the treatment was given. Further investigations are required to evaluate contributing factors of complications in thalassemia.
Asunto(s)
Deferasirox , Deferiprona , Quelantes del Hierro , Humanos , Deferiprona/uso terapéutico , Deferiprona/efectos adversos , Masculino , Femenino , Deferasirox/efectos adversos , Deferasirox/uso terapéutico , Deferasirox/economía , Estudios Retrospectivos , Quelantes del Hierro/economía , Quelantes del Hierro/uso terapéutico , Quelantes del Hierro/efectos adversos , Adulto , Adolescente , Niño , Talasemia/economía , Talasemia/tratamiento farmacológico , Adulto Joven , Indonesia , Talasemia beta/tratamiento farmacológico , Talasemia beta/economía , Talasemia beta/complicaciones , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/economía , Sobrecarga de Hierro/etiología , Preescolar , Terapia por Quelación/economía , Terapia por Quelación/efectos adversosRESUMEN
BACKGROUND: Transfusion-dependent haemoglobinopathies require lifelong iron chelation therapy with one of the three iron chelators (deferiprone, deferasirox, or deferoxamine). Deferasirox and deferiprone are the only two oral chelators used in adult patients with transfusion-dependent haemoglobinopathies. To our knowledge, there are no randomised clinical trials comparing deferiprone, a less expensive iron chelator, with deferasirox in paediatric patients. We aimed to show the non-inferiority of deferiprone versus deferasirox. METHODS: DEEP-2 was a phase 3, multicentre, randomised trial in paediatric patients (aged 1 month to 18 years) with transfusion-dependent haemoglobinopathies. The study was done in 21 research hospitals and universities in Italy, Egypt, Greece, Albania, Cyprus, Tunisia, and the UK. Participants were receiving at least 150 mL/kg per year of red blood cells for the past 2 years at the time of enrolment, and were receiving deferoxamine (<100 mg/kg per day) or deferasirox (<40 mg/kg per day; deferasirox is not registered for use in children aged <2 years so only deferoxamine was being used in these patients). Any previous chelation treatment was permitted with a 7-day washout period. Patients were randomly assigned 1:1 to receive orally administered daily deferiprone (75-100 mg/kg per day) or daily deferasirox (20-40 mg/kg per day) administered as dispersible tablets, both with dose adjustment for 12 months, stratified by age (<10 years and ≥10 years) and balanced by country. The primary efficacy endpoint was based on predefined success criteria for changes in serum ferritin concentration (all patients) and cardiac MRI T2-star (T2*; patients aged >10 years) to show non-inferiority of deferiprone versus deferasirox in the per-protocol population, defined as all randomly assigned patients who received the study drugs and had available data for both variables at baseline and after 1 year of treatment, without major protocol violations. Non-inferiority was based on the two-sided 95% CI of the difference in the proportion of patients with treatment success between the two groups and was shown if the lower limit of the two-sided 95% CI was greater than -12·5%. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with EudraCT, 2012-000353-31, and ClinicalTrials.gov, NCT01825512. FINDINGS: 435 patients were enrolled between March 17, 2014, and June 16, 2016, 393 of whom were randomly assigned to a treatment group (194 to the deferiprone group; 199 to the deferasirox group). 352 (90%) of 390 patients had ß-thalassaemia major, 27 (7%) had sickle cell disease, five (1%) had thalassodrepanocytosis, and six (2%) had other haemoglobinopathies. Median follow-up was 379 days (IQR 294-392) for deferiprone and 381 days (350-392) for deferasirox. Non-inferiority of deferiprone versus deferasirox was established (treatment success in 69 [55·2%] of 125 patients assigned deferiprone with primary composite efficacy endpoint data available at baseline and 1 year vs 80 [54·8%] of 146 assigned deferasirox, difference 0·4%; 95% CI -11·9 to 12·6). No significant difference between the groups was shown in the occurrence of serious and drug-related adverse events. Three (2%) cases of reversible agranulocytosis occurred in the 193 patients in the safety analysis in the deferiprone group and two (1%) cases of reversible renal and urinary disorders (one case of each) occurred in the 197 patients in the deferasirox group. Compliance was similar between treatment groups: 183 (95%) of 193 patients in the deferiprone group versus 192 (97%) of 197 patients in the deferisirox group. INTERPRETATION: In paediatric patients with transfusion-dependent haemoglobinopathies, deferiprone was effective and safe in inducing control of iron overload during 12 months of treatment. Considering the need for availability of more chelation treatments in paediatric populations, deferiprone offers a valuable treatment option for this age group. FUNDING: EU Seventh Framework Programme.
Asunto(s)
Deferasirox/uso terapéutico , Deferiprona/uso terapéutico , Transfusión de Eritrocitos/métodos , Hemoglobinopatías/tratamiento farmacológico , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/tratamiento farmacológico , Administración Oral , Adolescente , Agranulocitosis/inducido químicamente , Agranulocitosis/epidemiología , Albania/epidemiología , Anemia de Células Falciformes/terapia , Técnicas de Imagen Cardíaca/métodos , Niño , Preescolar , Chipre/epidemiología , Deferasirox/administración & dosificación , Deferasirox/economía , Deferiprona/administración & dosificación , Deferiprona/economía , Egipto/epidemiología , Transfusión de Eritrocitos/estadística & datos numéricos , Femenino , Ferritinas/sangre , Ferritinas/efectos de los fármacos , Grecia/epidemiología , Hemoglobinopatías/terapia , Humanos , Lactante , Quelantes del Hierro/administración & dosificación , Quelantes del Hierro/economía , Sobrecarga de Hierro/sangre , Italia/epidemiología , Imagen por Resonancia Magnética , Masculino , Cooperación del Paciente , Resultado del Tratamiento , Túnez/epidemiología , Reino Unido/epidemiología , Enfermedades Urológicas/inducido químicamente , Enfermedades Urológicas/epidemiología , Talasemia beta/terapiaRESUMEN
PURPOSE: Deferiprone (DFP), deferasirox (DFX) and deferoxamine (DFO) are used in thalassaemia major (TM) patients to treat chronic iron overload. We evaluated the cost-effectiveness of DFP, compared with DFX and DFO monotherapy, from an Italian healthcare system perspective. METHODS: A Markov model was used over a time horizon of 5 years. Italian-specific cost data were combined with Italian efficacy data. Costs and quality-adjusted life years (QALYs) were calculated for each treatment, with cost-effectiveness expressed as cost per QALY. RESULTS: In all scenarios modelled, DFP was the dominant treatment strategy. Sensitivity analyses showed that DFP dominated the other treatments with a >99% likelihood of being cost-effective against DFX and DFO at a willingness to pay threshold of 20,000 per QALY. CONCLUSIONS: DFP was the dominant and most cost-effective treatment for managing chronic iron overload in TM patients. Its use can result in substantial cost savings for the Italian healthcare system.
Asunto(s)
Análisis Costo-Beneficio/métodos , Costos de la Atención en Salud , Quelantes del Hierro/economía , Talasemia beta/tratamiento farmacológico , Talasemia beta/economía , Benzoatos/administración & dosificación , Benzoatos/economía , Estudios de Cohortes , Deferasirox , Deferiprona , Deferoxamina/administración & dosificación , Deferoxamina/economía , Vías de Administración de Medicamentos , Humanos , Quelantes del Hierro/administración & dosificación , Italia/epidemiología , Piridonas/administración & dosificación , Piridonas/economía , Resultado del Tratamiento , Triazoles/administración & dosificación , Triazoles/economía , Talasemia beta/epidemiologíaRESUMEN
BACKGROUND: Deferriferrichrysin (Dfcy) is a siderophore found in foods fermented by Aspergillus oryzae and is a promising candidate for an antioxidant food additive because of its high binding constant toward iron. However, the Dfcy concentration is typically low in foods and cultures. RESULTS: We optimised culture conditions to improve Dfcy production to 2800 mg L(-1) from 22.5 mg L(-1) under typical conditions. Then, we evaluated the potential of Dfcy as a food additive by measuring its safety, stability, and antioxidant activity. Dfcy was sufficiently stable that over 90% remained after pasteurisation at 63 °C for 30 min at pH 3-11, or after sterilisation at 120 °C for 4 min at pH 4-6. Dfcy showed high antioxidant activity in an oil-in-water model, where inhibition of lipid oxidation was measured by peroxide value (PV) and thiobarbituric acid reactive substances (TBARS) assays. Dfcy decreased PV and TBARS by 83% and 75%, respectively. Antioxidant activity of Dfcy was equal to or higher than that of the synthetic chelator EDTA. CONCLUSION: Our study provides the first practical method for production of Dfcy. Dfcy can be a novel food-grade antioxidant and the first natural alternative to the synthesised iron chelator EDTA. © 2015 Society of Chemical Industry.
Asunto(s)
Antioxidantes/aislamiento & purificación , Aspergillus oryzae/química , Conservantes de Alimentos/aislamiento & purificación , Quelantes del Hierro/aislamiento & purificación , Modelos Químicos , Péptido Hidrolasas/metabolismo , Péptidos Cíclicos/aislamiento & purificación , Animales , Antioxidantes/efectos adversos , Antioxidantes/química , Antioxidantes/economía , Aspergillus oryzae/crecimiento & desarrollo , Aspergillus oryzae/metabolismo , Fermentación , Conservantes de Alimentos/efectos adversos , Conservantes de Alimentos/química , Conservantes de Alimentos/economía , Industria de Procesamiento de Alimentos/economía , Proteínas Fúngicas/metabolismo , Calor/efectos adversos , Residuos Industriales/análisis , Residuos Industriales/economía , Quelantes del Hierro/efectos adversos , Quelantes del Hierro/química , Quelantes del Hierro/economía , Japón , Pruebas de Mutagenicidad , Oryza/química , Péptidos Cíclicos/efectos adversos , Péptidos Cíclicos/química , Péptidos Cíclicos/economía , Proteínas de Vegetales Comestibles/química , Proteínas de Vegetales Comestibles/economía , Proteínas de Vegetales Comestibles/aislamiento & purificación , Proteínas de Vegetales Comestibles/metabolismo , Hidrolisados de Proteína/química , Hidrolisados de Proteína/economía , Hidrolisados de Proteína/aislamiento & purificación , Hidrolisados de Proteína/metabolismo , Saccharomyces cerevisiae/crecimiento & desarrollo , Saccharomyces cerevisiae/metabolismo , Semillas/química , Pruebas de Toxicidad Aguda , Vino/análisis , Vino/microbiologíaRESUMEN
BACKGROUND: Sub-optimal patient adherence to iron chelation therapy (ICT) may impact patient outcomes and increase cost of care. This study evaluated the economic burden of ICT non-adherence in patients with sickle cell disease (SCD) or thalassemia. METHODS: Patients with SCD or thalassemia were identified from six state Medicaid programs (1997-2013). Adherence was estimated using the medication possession ratio (MPR) of ≥0.80. All-cause and disease-specific resource utilization per-patient-per-month (PPPM) was assessed and compared between adherent and non-adherent patients using adjusted incidence rate ratios (aIRR). All-cause and disease-specific healthcare costs were computed using mean cost PPPM. Regression models adjusting for baseline characteristics were used to compare adherent and non-adherent patients. RESULTS: A total of 728 eligible patients treated with ICT in the SCD cohort, 461 (63%) adherent, and 218 in the thalassemia cohort, 137 (63%) adherent, were included in this study. In SCD patients, the adjusted rate of all-cause outpatient visits PPPM was higher in adherent patients vs non-adherent patients (aIRR [95% CI]: 1.05 [1.01-1.08], p < 0.0001). Conversely, adherent patients incurred fewer all-cause inpatients visits (0.87 [0.81-0.94], p < 0.001) and ER visits (0.86 [0.78-0.93], p < 0.001). Similar trends were observed in SCD-related resource utilization rates and in thalassemia patients. Total all-cause costs were similar between adherent and non-adherent patients, but inpatient costs (adjusted cost difference = -$1530 PPPM, p = 0.0360) were lower in adherent patients. CONCLUSION: Patients adherent to ICT had less acute care need and lower inpatient costs than non-adherent patients, although they had more outpatient visits. Improved adherence may be linked to better disease monitoring and has the potential to avoid important downstream costs associated with acute care visits and reduce the financial burden on health programs and managed care plans treating SCD and thalassemia patients.
Asunto(s)
Anemia de Células Falciformes/tratamiento farmacológico , Terapia por Quelación/economía , Quelantes del Hierro/economía , Quelantes del Hierro/uso terapéutico , Medicaid/economía , Cumplimiento de la Medicación , Talasemia/tratamiento farmacológico , Adolescente , Adulto , Comorbilidad , Femenino , Costos de la Atención en Salud , Humanos , Revisión de Utilización de Seguros , Estudios Longitudinales , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Estados UnidosRESUMEN
Iron chelation therapies (ICTs) can help eliminate iron surplus in erythrocyte transfusion-dependent (TD) patients with myelofibrosis (MF). The study assessed adjusted incidence rate ratios (aIRRs) of MF-related complications and resource utilization (RU) and adjusted mean monthly inpatient cost differences in patients with TD MF treated with versus without ICT (ICT+ vs. ICT-) using data from two healthcare claims databases. Patients with ≥ 2 MF International Classification of Diseases, 9th Revision (ICD-9) diagnosis codes ≥ 30 days apart were included. Among 571 patients with TD MF, 103 (18%) were ICT+ and 468 (82%) were ICT-. ICT+ patients had lower rates of thrombocytopenia (aIRR: 0.55; p < 0.001), pancytopenia (0.53; p < 0.001), emergency room visits (0.84 [95% confidence interval: 0.74-0.96]) and inpatient stays (0.75 [0.64-0.87]), but higher rates of outpatient visits (1.21 [1.18-1.23]). Adjusted mean complication-related inpatient cost difference per month was lower in ICT+ patients (-$1804 [$570]; p = 0.004). ICT+ patients had significantly lower rates of acute care, but higher rates of outpatient care.
Asunto(s)
Transfusión Sanguínea , Terapia por Quelación , Costos de la Atención en Salud , Recursos en Salud , Quelantes del Hierro , Mielofibrosis Primaria/complicaciones , Mielofibrosis Primaria/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Transfusión Sanguínea/economía , Terapia por Quelación/economía , Bases de Datos Factuales , Transfusión de Eritrocitos/efectos adversos , Transfusión de Eritrocitos/economía , Femenino , Recursos en Salud/economía , Humanos , Incidencia , Seguro de Salud , Quelantes del Hierro/economía , Quelantes del Hierro/uso terapéutico , Masculino , Persona de Mediana Edad , Prevalencia , Mielofibrosis Primaria/terapia , Estudios Retrospectivos , Reacción a la Transfusión , Estados Unidos/epidemiología , Adulto JovenRESUMEN
In the inherited hematologic disorder ß-thalassemia major, patients receive regular, lifelong blood transfusions, which carry excess iron that the body is unable to eliminate. Chelation therapy (deferoxamine, deferiprone, deferasirox or deferoxamine-deferiprone combination) is required to reduce iron accumulation in target organs and the associated morbidity and mortality. Each chelation regimen has a distinct safety/efficacy profile and particular costs associated with its use. This review aims to provide an overview of published cost-utility analyses of currently used chelation regimens, and to comment on the potential relevance of their findings in the USA market, where deferiprone has recently been introduced.
Asunto(s)
Transfusión Sanguínea/economía , Costos de los Medicamentos , Quelantes del Hierro/economía , Quelantes del Hierro/uso terapéutico , Talasemia beta/economía , Talasemia beta/terapia , Análisis Costo-Beneficio , Quimioterapia Combinada , Humanos , Modelos Económicos , Reacción a la Transfusión , Resultado del Tratamiento , Talasemia beta/sangre , Talasemia beta/diagnósticoRESUMEN
BACKGROUND: Patients with ß-thalassaemia major experience chronic iron overload due to regular blood transfusions. Chronic iron overload can be treated using iron-chelating therapies such as desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) monotherapy, or DFO-DFP combination therapy. OBJECTIVES: This study evaluated the relative cost effectiveness of these regimens over a 5-year timeframe from a UK National Health Service (NHS) perspective, including personal and social services. METHODS: A Markov model was constructed to evaluate the cost effectiveness of the treatment regimens over 5 years. Based on published randomized controlled trial evidence, it was assumed that all four treatment regimens had a comparable effect on serum ferritin concentration (SFC) and liver iron concentration (LIC), and that DFP was more effective for reducing cardiac morbidity and mortality. Published utility scores for route of administration were used, with subcutaneously administered DFO assumed to incur a greater quality of life (QoL) burden than the oral chelators DFP and DFX. Healthcare resource use, drug costs (2010/2011 costs), and utilities associated with adverse events were also considered, with the effect of varying all parameters assessed in sensitivity analysis. Incremental costs and quality-adjusted life-years (QALYs) were calculated for each treatment, with cost effectiveness expressed as incremental cost per QALY. Assumptions that DFP conferred no cardiac morbidity, mortality, or morbidity and mortality benefit were also explored in scenario analysis. RESULTS: DFP was the dominant strategy in all scenarios modelled, providing greater QALY gains at a lower cost. Sensitivity analysis showed that DFP dominated all other treatments unless the QoL burden associated with the route of administration was greater for DFP than for DFO, which is unlikely to be the case. DFP had >99 % likelihood of being cost effective against all comparators at a willingness-to-pay threshold of £20,000 per QALY. CONCLUSIONS: In this analysis, DFP appeared to be the most cost-effective treatment available for managing chronic iron overload in ß-thalassaemia patients. Use of DFP in these patients could therefore result in substantial cost savings.
Asunto(s)
Quelantes del Hierro/economía , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/economía , Piridonas/economía , Piridonas/uso terapéutico , Talasemia beta/complicaciones , Talasemia beta/economía , Análisis Costo-Beneficio/economía , Deferiprona , Costos de los Medicamentos , Costos de la Atención en Salud , Humanos , Quelantes del Hierro/efectos adversos , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/complicaciones , Modelos Económicos , Piridonas/efectos adversos , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Reino Unido , Talasemia beta/tratamiento farmacológicoRESUMEN
During the last 30 years, in addition to the considerable progress made in control and prevention of thalassemias(3), there have also been major advances in their symptomatic management, at least in wealthier countries where appropriate facilities are available. Remarkable improvements in survival in the severe forms of thalassemia have followed the more judicious use of blood transfusion and, in particular, the ability to manage the iron accumulation resulting from transfusion with its severe and ultimately lethal effects on endocrine and cardiac function.
Asunto(s)
Talasemia/terapia , Benzoatos/economía , Benzoatos/uso terapéutico , Transfusión Sanguínea , Deferasirox , Deferiprona , Deferoxamina/economía , Deferoxamina/uso terapéutico , Ferritinas/sangre , Humanos , Hierro/metabolismo , Quelantes del Hierro/economía , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/terapia , Hígado/metabolismo , Miocardio/metabolismo , Páncreas/metabolismo , Adenohipófisis/metabolismo , Piridonas/economía , Piridonas/uso terapéutico , Triazoles/economía , Triazoles/uso terapéuticoRESUMEN
BACKGROUND/PURPOSE: The newly available iron chelator deferasirox (Exjade, Novartis) is expected to provide better long-term clinical outcomes and improved quality of life for patients with thalassemia than its predecessor, deferoxamine (Desferal, Novartis), because of its oral tablet form. METHODS: We used the Markov model to estimate total additional lifetime costs and quality-adjusted life years (QALYs) gained with deferasirox versus deferoxamine in patients with transfusion-dependent thalassemia. Patients were assumed to be 2 years of age at initiation of chelation therapy. Clinical outcomes in terms of morbidity and mortality from associated complications and life expectancy for the study population were estimated using the databases of the Bureau of National Health Insurance and the Health and Vital Statistics of Taiwan. Treatment costs were based on analyses of health insurance claims for patients with transfusion-dependent thalassemia. Utilities in terms of quality of life were also included in the model. The incremental cost-utility ratio of deferasirox versus deferoxamine was defined by the ratio of the difference in expected lifetime costs to the difference in QALYs. One-way sensitivity analyses were performed to examine the robustness of the results to key assumptions. RESULTS: Patients treated with deferasirox are expected to experience a lower incidence of associated complications and obtain 2.3 QALYs (discounted) at an additional lifetime cost of US$36,291 per patient (US$15,596 per QALY). Sensitivity analyses showed that the unit drug cost of deferasirox had the greatest impact on the incremental cost-utility ratio. In addition, the incremental cost-utility ratio will increase by delaying the starting age (2 years of age in our study) of chelation therapy. CONCLUSION: Compared with infusional deferoxamine, oral deferasirox improved clinical outcomes and quality of life in terms of iron chelation in transfusion-dependent patients with thalassemia at a reasonable cost from a healthcare perspective.
Asunto(s)
Benzoatos/uso terapéutico , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/tratamiento farmacológico , Talasemia/complicaciones , Triazoles/uso terapéutico , Benzoatos/economía , Preescolar , Deferasirox , Deferoxamina/uso terapéutico , Costos de la Atención en Salud , Humanos , Quelantes del Hierro/economía , Cadenas de Markov , Años de Vida Ajustados por Calidad de Vida , Reacción a la Transfusión , Triazoles/economíaRESUMEN
BACKGROUND: Hematopoieticic stem cell transplantation is the only therapeutic option that can cure thalassemia disease. Reduced intensity hematopoietic stem cell transplantation (RI-HSCT) has demonstrated a high cure rate with minimal complications compared to other options. Because RI-HSCT is very costly, economic justification for its value is needed. This study aimed to estimate the cost-utility of RI-HSCT compared with blood transfusions combined with iron chelating therapy (BT-ICT) for adolescent and young adult with severe thalassemia in Thailand. METHODS: A Markov model was used to estimate the relevant costs and health outcomes over the patients' lifetimes using a societal perspective. All future costs and outcomes were discounted at a rate of 3% per annum. The efficacy of RI-HSCT was based a clinical trial including a total of 18 thalassemia patients. Utility values were derived directly from all patients using EQ-5D and SF-6D. Primary outcomes of interest were lifetime costs, quality adjusted life-years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) in US ($) per QALY gained. One-way and probabilistic sensitivity analyses (PSA) were conducted to investigate the effect of parameter uncertainty. RESULTS: In base case analysis, the RI-HSCT group had a better clinical outcomes and higher lifetime costs. The incremental cost per QALY gained was US $3,236 per QALY. The acceptability curve showed that the probability of RI-HSCT being cost-effective was 71% at the willingness to pay of 1 time of Thai Gross domestic product per capita (GDP per capita), approximately US $4,210 per QALY gained. The most sensitive parameter was utility of severe thalassemia patients without cardiac complication patients. CONCLUSION: At a societal willingness to pay of 1 GDP per capita, RI-HSCT was a cost-effective treatment for adolescent and young adult with severe thalassemia in Thailand compared to BT-ICT.
Asunto(s)
Transfusión Sanguínea/economía , Transfusión Sanguínea/métodos , Trasplante de Células Madre Hematopoyéticas/economía , Quelantes del Hierro/uso terapéutico , Talasemia/terapia , Adolescente , Niño , Análisis Costo-Beneficio , Femenino , Humanos , Quelantes del Hierro/economía , Masculino , Cadenas de Markov , Modelos Económicos , Índice de Severidad de la Enfermedad , TailandiaRESUMEN
BACKGROUND: This study explored the blood transfusion patterns, SCD complications, utilization of iron chelation therapies (ICT), healthcare resource use, and costs in pediatric, transitioning (18 years old) and adult patients with SCD. PROCEDURE: Data from Florida (1998-2009), New Jersey (1996-2009), Missouri (1997-2010), Kansas (2001-2009), and Iowa (1998-2010) state Medicaid were used. Patients with ≥2 SCD diagnoses and ≥1 transfusion event were included. Rates of transfusion events, SCD complications, and proportion of eligible patients receiving ICT were calculated. ICT eligibility was defined as receiving ≥10 transfusions over lifetime. SCD complications included pain, pulmonary event, infection event, renal, cardiovascular, stroke, leg ulcers, and avascular necrosis. Regressions were used to assess risk factors for transfusion and identify the main drivers of costs. RESULTS: The sample included 3,208 patients. The transfusion rate increased from 1-year-old to a peak at 16 years old, then dropped until age 26 and remained stable thereafter. In contrast the frequency of diagnoses for SCD complications increased markedly after age 16. Post-transition patients (≥18 years old) were significantly associated with fewer transfusions (odds ratio: 0.80, P = 0.002). Among eligible patients for ICT, there was no statistically significant difference in total cost between the ICT and no ICT groups (adjusted cost difference, $136, P = 0.114). CONCLUSIONS: Patients transitioning to adult care received less transfusions and hydroxyurea, less ICT when eligible for chelation therapy, had higher healthcare costs and suffered from more frequent SCD related complications than pediatric patients. These findings highlight the changes in treatment patterns corresponding to transition to adult care.
Asunto(s)
Anemia de Células Falciformes , Transfusión Sanguínea , Costos de la Atención en Salud , Quelantes del Hierro/uso terapéutico , Adolescente , Adulto , Factores de Edad , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/economía , Anemia de Células Falciformes/epidemiología , Terapia por Quelación , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Hidroxiurea/uso terapéutico , Lactante , Recién Nacido , Quelantes del Hierro/economía , Estudios Longitudinales , Masculino , Medicaid , Persona de Mediana Edad , Estudios Retrospectivos , Accidente Cerebrovascular/etiología , Resultado del Tratamiento , Estados Unidos/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: This retrospective study evaluated iron chelating therapy (ICT) discontinuation and costs in Sickle cell disease (SCD) Medicaid recipients using healthcare claims from 2006-2010. METHODS: Patients with ≥1 SCD diagnosis claim, ≥2 claims for deferoxamine (DFO) or deferosirox (DFX), and continuous enrollment ≥6 months prior to and 18 months following ICT initiation were included. Outcomes included treatment discontinuation, persistence (i.e., refill gaps ≥6 weeks), and total healthcare costs. RESULTS: The average age among 404 SCD patients meeting study inclusion criteria was 18.7 (±11.0) years, with 45.8% being males and 66.7% being Blacks. Switches or combinations from DFO at index occurred in 124 (74.7%) patients compared to 10 (4.2%) with DFX at index. The Cox regression model that assessed long-term medication persistence indicated a 1.30-times higher likelihood of treatment discontinuation with DFO compared to DFX (95% CI: 1.06-1.61). Some 19.7% of patient remained on DFX relative to 4.8% on DFO. Both inpatient and total costs were similar in DFX and DFO treatment groups. Following 1 year of treatment, 37.4% remained on DFX compared to 15.7% on DFO. Meaningful differences in treatment discontinuation between the two treatment groups did not occur until 220+ days during the study period. At 18-months, treatment discontinuation rates were high in both groups; 95% for DFO and 80% for DFX. CONCLUSION: This study of SCD Medicaid patients found more therapeutic switches from DFO to DFX and a higher medication persistency rate with DFX than DFO. The conclusions are limited by the study's retrospective nature, which depends on multivariate statistics to account for patient heterogeneity and risk factors.
Asunto(s)
Anemia de Células Falciformes/tratamiento farmacológico , Benzoatos/economía , Deferoxamina/economía , Quelantes del Hierro/economía , Medicaid/estadística & datos numéricos , Triazoles/economía , Adolescente , Adulto , Factores de Edad , Anemia de Células Falciformes/economía , Anemia de Células Falciformes/epidemiología , Benzoatos/uso terapéutico , Transfusión Sanguínea , Niño , Deferasirox , Deferoxamina/uso terapéutico , Utilización de Medicamentos , Femenino , Gastos en Salud , Humanos , Revisión de Utilización de Seguros/estadística & datos numéricos , Quelantes del Hierro/uso terapéutico , Estimación de Kaplan-Meier , Masculino , Cumplimiento de la Medicación/estadística & datos numéricos , Prioridad del Paciente/estadística & datos numéricos , Modelos de Riesgos Proporcionales , Grupos Raciales/estadística & datos numéricos , Estudios Retrospectivos , Factores Sexuales , Triazoles/uso terapéutico , Estados UnidosRESUMEN
BACKGROUND: Deferasirox (DFX) is a novel iron chelator that has been shown to have similar efficacy and safety compared with deferoxamine (DFO) in patients with ß-thalassemia. The aim of this study was to determine the cost utility of DFX versus DFO in ß-thalassemia major patients from Iran's society perspective. STUDY DESIGN AND METHODS: A Markov model has been developed to determine lifetime cost and quality-adjusted life-years (QALYs) of patients. To estimate the annual cost of each method, a cross-sectional study was conducted among two groups of patients who received DFO and DFX (n = 100 and n = 45, respectively). Also a time trade-off method was used to estimate the utility of two strategies. Finally a one-way and probabilistic sensitivity analysis was conducted to examine the strength of the results. RESULTS: Our base-case analysis showed that estimated total lifetime costs per patient for DFX and DFO were 47,029 international dollar ($Int) and $Int143,522, respectively, while the estimated total discounted QALYs per person were 12.28 and 7.76, respectively. Calculated incremental cost-effectiveness ratio showed that DSX is a dominant therapy and its estimated lifetime net monetary benefit was $Int273,528. CONCLUSION: We conclude that the use of DFX instead of DFO represents a cost-effective use of resources for treatment of iron overload in patients with ß-thalassemia from Iran's society perspective.
Asunto(s)
Benzoatos/uso terapéutico , Deferoxamina/uso terapéutico , Costos de los Medicamentos/estadística & datos numéricos , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/tratamiento farmacológico , Reacción a la Transfusión , Triazoles/uso terapéutico , Talasemia beta/terapia , Administración Oral , Adulto , Benzoatos/economía , Análisis Costo-Beneficio , Estudios Transversales , Deferasirox , Deferoxamina/economía , Femenino , Humanos , Infusiones Intravenosas , Irán , Quelantes del Hierro/economía , Sobrecarga de Hierro/economía , Sobrecarga de Hierro/etiología , Masculino , Cadenas de Markov , Modelos Económicos , Años de Vida Ajustados por Calidad de Vida , Resultado del Tratamiento , Triazoles/economía , Talasemia beta/complicaciones , Talasemia beta/economíaRESUMEN
BACKGROUND AND OBJECTIVES: Regular blood transfusions for beta-thalassaemia patients lead to the accumulation of iron deposits in the body. In order to remove such deposits, iron chelation therapy is required. Subcutaneously administered deferoxamine has been the gold standard chelation therapy for over 40 years. Deferasirox is a newer chelation therapy that is taken orally once daily. The objective of this study was to estimate the long-term costs and quality-adjusted life-years (QALYs) associated with deferoxamine and deferasirox in a cohort of transfusion-dependent beta-thalassaemia patients from a UK health service perspective. METHODS: A 50-year annual cycle state transition model comprised three core health states: alive without cardiac complications, alive with cardiac complications, and dead, as well as representing other chronic complications of iron overload: diabetes, hypogonadism, hypoparathyroidism and hypothyroidism. The model was calibrated to identify sets of convergent input parameter values that predicted observed overall survival by mean lifetime compliance with chelation therapy. A pivotal non-inferiority trial informed the main estimates of the effectiveness of deferasirox, which were applied to the calibrated model. Using cost values for the year 2011, costs and utilities were summed over patients' lifetimes to estimate lifetime costs and QALY gains. RESULTS: Mean lifetime treatment costs for patients receiving deferoxamine were £70,000 higher than deferasirox. Drug acquisition costs were £100,000 higher for deferasirox, but administration costs associated with deferoxamine were £170,000 higher. Higher compliance associated with oral deferasirox administration led to fewer complications. Combined with the quality-of-life effects of an oral mode of administration, an average gain of 4.85 QALYs for deferasirox was estimated. In the base case, deferasirox dominates deferoxamine, i.e., costs less and patients gain more QALYs. The key parameter is the proportion of deferoxamine patients using balloon infusers. Sensitivity analyses showed that even when the proportion of patients using balloon infusers is decreased from 79 to 25 %, the incremental cost per QALY gained remains well under £20,000. CONCLUSION: Higher drug acquisition costs for deferasirox are offset by the avoidance of infusion-related equipment costs. Combined with health benefits derived from an oral mode of administration and improved compliance, deferasirox has a high probability of being a cost-effective intervention compared with deferoxamine.
Asunto(s)
Benzoatos/uso terapéutico , Deferoxamina/uso terapéutico , Quelantes del Hierro/uso terapéutico , Triazoles/uso terapéutico , Talasemia beta/tratamiento farmacológico , Administración Oral , Benzoatos/administración & dosificación , Benzoatos/economía , Transfusión Sanguínea/economía , Transfusión Sanguínea/métodos , Estudios de Cohortes , Análisis Costo-Beneficio , Deferasirox , Deferoxamina/administración & dosificación , Deferoxamina/economía , Costos de los Medicamentos , Humanos , Inyecciones Subcutáneas , Quelantes del Hierro/administración & dosificación , Quelantes del Hierro/economía , Sobrecarga de Hierro/complicaciones , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/economía , Cumplimiento de la Medicación , Modelos Económicos , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Tasa de Supervivencia , Triazoles/administración & dosificación , Triazoles/economía , Reino Unido , Talasemia beta/complicaciones , Talasemia beta/economíaRESUMEN
Blood transfusions may prevent and treat serious complications related to sickle-cell disease (SCD) when performed according to specific guidelines. However, blood transfusion requirements in SCD inevitably lead to increased body iron burden. An adequate chelation treatment may prevent complications and reduce morbidity and mortality. This review evaluates the effectiveness, safety and costs of chelation treatment. The included trials were examined according to the recommendations of the American College of Cardiology (ACC) and the American Heart Association (AHA). Overall, 14 trials and a total of 502 patients with SCD were included in this review. Deferoxamine alone (s.c. or i.v.), deferiprone alone or versus deferoxamine, deferasirox versus deferoxamine and combined treatment with deferoxamine plus deferiprone were included and evaluated in the analysis. Only two randomized clinical trials have been reported. The results of this analysis suggest that use of chelation treatment in SCD to date has been based on little efficacy and safety evidence, although it is widely recommended and practised. The cost/benefit ratio has not been fully explored. Further research with larger randomized clinical trials needs to be performed.
Asunto(s)
Anemia de Células Falciformes/tratamiento farmacológico , Terapia por Quelación , Quelantes del Hierro/uso terapéutico , Costos y Análisis de Costo , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Quelantes del Hierro/efectos adversos , Quelantes del Hierro/economía , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVE: ß-Thalassaemia is a major public health problem in Thailand. Use of appropriate iron-chelating agents could prevent thalassaemia-related complications, which are costly to the healthcare system. This study aimed to evaluate the cost effectiveness of deferoxamine (DFO), deferiprone (DFP) and deferasirox (DFX) in Thai transfusion-dependent ß-thalassaemia patients from the societal perspective. METHODS: A Markov model was used to project the life-time costs and outcomes represented as quality-adjusted life-years (QALYs). Data on the clinical efficacy and safety of all therapeutic options were obtained from a systematic review and clinical trials. Transition probabilities were derived from published studies. Costs were obtained from the Thai Drug and Medical Supply Information Center, Thai national reimbursement rate information and other Thai literature sources. A discount rate of 3% was used. Incremental cost-effectiveness ratios (ICERs) were presented as year 2009 values. A base-case analysis was performed for thalassaemia patients requiring regular blood transfusion therapy, while a separate analysis was performed for patients requiring low (i.e. symptom-dependent, less frequent) blood transfusion therapy. A series of sensitivity analysis and cost-effectiveness acceptability curves were constructed. RESULTS: Compared with DFO, using DFP was dominant with lifetime cost savings of $US91 117. Comparing DFX with DFO, the incremental cost was $US522 863 and incremental QALY was 5.77 with an ICER of $US90 648 per QALY. When compared with DFP, the ICER of DFX was $US106 445 per QALY. A cost-effectiveness analysis curve showed the probability of DFX being cost effective was 0% when compared with either DFO or DFP, based on the cost-effectiveness cut-off value of $US2902 per QALY. When compared with DFP, DFX was cost effective only if the DFX cost was as low as $US1.68 per 250 mg tablet. The results of the analysis in patients requiring low blood transfusion therapy were not different from those of the base-case analysis. CONCLUSIONS: Our findings suggest that using DFP is cost saving when compared with conventional therapy, while using DFX is not cost effective compared with either DFO or DFP in Thai patients with transfusion-dependent ß-thalassaemia. Policy-makers and clinicians may consider using such information in their decision-making process in Thailand.
Asunto(s)
Transfusión Sanguínea/economía , Análisis Costo-Beneficio/métodos , Costos de la Atención en Salud/estadística & datos numéricos , Quelantes del Hierro/economía , Talasemia beta/economía , Benzoatos/economía , Benzoatos/uso terapéutico , Deferasirox , Deferiprona , Deferoxamina/economía , Deferoxamina/uso terapéutico , Humanos , Quelantes del Hierro/uso terapéutico , Cadenas de Markov , Modelos Económicos , Piridonas/economía , Piridonas/uso terapéutico , Años de Vida Ajustados por Calidad de Vida , Tailandia , Triazoles/economía , Triazoles/uso terapéutico , Talasemia beta/tratamiento farmacológico , Talasemia beta/terapiaRESUMEN
Rice bran, a byproduct of the rice milling process, contains most of the phytochemicals. This study aimed at determining the concentrations of lipophilic, solvent-extractable (free), and cell wall-bound (bound) phytochemicals and their antioxidant capacities from brans of white, light brown, brown, purple, and red colors, and broccoli and blueberry for comparison. The concentrations of lipophilic antioxidants of vitamin E (tocopherol and tocotrienols) and γ-oryzanols were 319.67 to 443.73 and 3861.93 to 5911.12 µg/g bran dry weight (DW), respectively, and were not associated with bran color. The total phenolic, total flavonoid, and antioxidant capacities of ORAC (oxygen radical absorbance capacity), DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging, and iron-chelating in the free fraction were correlated with the intensity of bran color, while variations of these in the bound fraction were less than those in the free fraction among brans. Compounds in the bound fraction had higher antioxidant capacity of ORAC than DPPH, relative to those in the free fraction. The bound fraction of light-color brans contributed as much to its total ORAC as the free fraction. Total proanthocyanidin concentration was the highest in red rice bran, while total anthocyanin was highest in purple brans. The predominant anthocyanin was cyanidin-3-glucoside. Red and purple brans had several fold higher total phenolics and flavonoids as well as ORAC and DPPH, from both free and bound fractions, than freeze-dried blueberry and broccoli. These results indicate that rice brans are natural sources of hydrophilic and lipophilic phytochemicals for use in quality control of various food systems as well as for nutraceutical and functional food application.
Asunto(s)
Antioxidantes/análisis , Fibras de la Dieta/análisis , Flavonoides/análisis , Oryza/química , Fenoles/análisis , Semillas/química , Antocianinas/análisis , Antocianinas/química , Antocianinas/economía , Antioxidantes/química , Antioxidantes/economía , Pared Celular/química , Flavonoides/química , Flavonoides/economía , Aditivos Alimentarios/análisis , Aditivos Alimentarios/química , Aditivos Alimentarios/economía , Industria de Procesamiento de Alimentos/economía , Depuradores de Radicales Libres/análisis , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/economía , Interacciones Hidrofóbicas e Hidrofílicas , Residuos Industriales/análisis , Residuos Industriales/economía , Quelantes del Hierro/análisis , Quelantes del Hierro/química , Quelantes del Hierro/economía , Fenoles/química , Fenoles/economía , Fenilpropionatos/análisis , Fenilpropionatos/química , Fenilpropionatos/economía , Pigmentación , Polifenoles , Proantocianidinas/análisis , Proantocianidinas/química , Proantocianidinas/economía , Solubilidad , Especificidad de la Especie , Vitamina E/análisis , Vitamina E/química , Vitamina E/economíaRESUMEN
Consideration of iron-chelation (IC) in transfusion-dependent patients is recommended in most clinical-practice guidelines on myelodysplastic syndromes (MDS). The financial impact of IC on health-care systems is predicted through economic modeling, but an analysis based on actual prevalence is lacking. Here, we have investigated the potential drug-costs and need for IC in a cohort of 189 United Kingdom-based MDS patients diagnosed from 2000 to 2010. Patients with low or intermediate-1 IPSS scores were identified as eligible for IC if ≥24 red cell units (RCU) had been transfused over 12 consecutive months or the transfusion-intensity averaged ≥2 RCU per month. Drug-costs were calculated from the time patients qualified for IC until death or last follow-up. In 159 patients with low/intermediate-1 MDS, survival was superior with a low IPSS score (P = 0.014), age <70 years (P = 0.043), transfusion-independence at diagnosis (P = 0.0056) and transfusion-intensity of <2 RCU per month (P = 0.009). Reflecting the time elapsed since diagnosis, longer survival was observed with a cumulative red cell load of ≥75 U (P = 0.046). By logistic-regression analysis, transfusion-intensity independently predicted survival (P = 0.0035) in low and intermediate-1 risk MDS patients. Forty-one patients fulfilled criteria for consideration of IC. Of these, 6 patients died within 1 month; 35 patients survived for a median of 16 months (range 1-61). Had patients commenced IC, the anticipated drug-costs alone would have been ~$526,880-$2,064,800 over 10 years. The lack of association between cumulative transfusion-load and survival calls for a prospective evaluation of the cost-utility of IC in patients surviving long-term, to enable evidence-based recommendations in MDS management.
Asunto(s)
Terapia por Quelación/economía , Costos de los Medicamentos , Transfusión de Eritrocitos , Quelantes del Hierro/economía , Síndromes Mielodisplásicos/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anemia/epidemiología , Anemia/etiología , Anemia/terapia , Estudios de Cohortes , Análisis Costo-Beneficio , Transfusión de Eritrocitos/efectos adversos , Transfusión de Eritrocitos/estadística & datos numéricos , Hemosiderosis/epidemiología , Hemosiderosis/prevención & control , Humanos , Quelantes del Hierro/uso terapéutico , Persona de Mediana Edad , Síndromes Mielodisplásicos/economía , Síndromes Mielodisplásicos/fisiopatología , Prevalencia , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Reino Unido/epidemiologíaRESUMEN
OBJECTIVE: The study evaluated the cost effectiveness of deferasirox (Exjade * ) compared to non-proprietary desferrioxamine (DFO) for the control of transfusional iron overload in lower risk myelodysplastic syndromes (MDS) patients. A UK National Health Service perspective was adopted. METHODS: Recent clinical evidence has demonstrated the efficacy and safety of deferasirox in transfusion-dependent MDS patients with elevated serum ferritin levels. An economic model was used to extrapolate the clinical benefits of iron chelation therapy (ICT) in a cohort of lower risk MDS patients. Costs for drug acquisition, drug administration and monitoring, and quality of life (utility) outcomes associated with mode of drug administration were derived from a variety of sources. The incremental cost per QALY gained for deferasirox was estimated. Costs and outcomes were discounted at 3.5% in line with UK standards. RESULTS: The base-case cost effectiveness of deferasirox versus DFO was estimated to be £20,822 per QALY gained, the key driver being the additional quality of life benefits associated with a simpler mode of administration for deferasirox. A mean survival benefit for both forms of ICT of 4.5 years was estimated. The results were sensitive to drug dose, days of DFO administration, and patient weight. CONCLUSIONS: In the UK, a cost per QALY below £20,000-30,000 is considered cost effective. Hence, the results from this economic analysis suggest deferasirox is cost effective in lower risk, transfusion-dependent, MDS patients. Limitations with the analysis include a lack of comparative randomised controlled trial evidence, in particular to differentiate survival and clinical outcomes for deferasirox and DFO.