RESUMO
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.
Assuntos
Deferasirox , Deferiprona , Quelantes de Ferro , Humanos , Deferiprona/uso terapêutico , Deferiprona/efeitos adversos , Masculino , Feminino , Deferasirox/efeitos adversos , Deferasirox/uso terapêutico , Deferasirox/economia , Estudos Retrospectivos , Quelantes de Ferro/economia , Quelantes de Ferro/uso terapêutico , Quelantes de Ferro/efeitos adversos , Adulto , Adolescente , Criança , Talassemia/economia , Talassemia/tratamento farmacológico , Adulto Jovem , Indonésia , Talassemia beta/tratamento farmacológico , Talassemia beta/economia , Talassemia beta/complicações , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/economia , Sobrecarga de Ferro/etiologia , Pré-Escolar , Terapia por Quelação/economia , Terapia por Quelação/efeitos adversosRESUMO
The design of clinical protocols and the selection of drugs with appropriate posology are critical parameters for therapeutic outcomes. Optimal therapeutic protocols could ideally be designed in all diseases including for millions of patients affected by excess iron deposition (EID) toxicity based on personalised medicine parameters, as well as many variations and limitations. EID is an adverse prognostic factor for all diseases and especially for millions of chronically red-blood-cell-transfused patients. Differences in iron chelation therapy posology cause disappointing results in neurodegenerative diseases at low doses, but lifesaving outcomes in thalassemia major (TM) when using higher doses. In particular, the transformation of TM from a fatal to a chronic disease has been achieved using effective doses of oral deferiprone (L1), which improved compliance and cleared excess toxic iron from the heart associated with increased mortality in TM. Furthermore, effective L1 and L1/deferoxamine combination posology resulted in the complete elimination of EID and the maintenance of normal iron store levels in TM. The selection of effective chelation protocols has been monitored by MRI T2* diagnosis for EID levels in different organs. Millions of other iron-loaded patients with sickle cell anemia, myelodysplasia and haemopoietic stem cell transplantation, or non-iron-loaded categories with EID in different organs could also benefit from such chelation therapy advances. Drawbacks of chelation therapy include drug toxicity in some patients and also the wide use of suboptimal chelation protocols, resulting in ineffective therapies. Drug metabolic effects, and interactions with other metals, drugs and dietary molecules also affected iron chelation therapy. Drug selection and the identification of effective or optimal dose protocols are essential for positive therapeutic outcomes in the use of chelating drugs in TM and other iron-loaded and non-iron-loaded conditions, as well as general iron toxicity.
Assuntos
Sobrecarga de Ferro , Talassemia beta , Humanos , Deferiprona/uso terapêutico , Desferroxamina/uso terapêutico , Piridonas/efeitos adversos , Quelantes de Ferro/efeitos adversos , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/induzido quimicamente , Terapia por Quelação/métodos , Ferro/metabolismo , Talassemia beta/tratamento farmacológico , Talassemia beta/complicações , Quimioterapia CombinadaRESUMO
Transfusion-dependent patients typically develop iron-induced cardiomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusiondependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX). We developed a multi-center follow-up study of 426 TDT patients treated with once-daily DFX for a median duration of 8 years, up to 18.5 years. At baseline, 118, 121, and 187 patients had 0, 1, or ≥2 endocrine diseases respectively. 104 additional endocrine diseases were developed during the follow-up. The overall risk of developing a new endocrine complication within 5 years was 9.7% (95% Confidence Interval [CI]: 6.3-13.1). Multiple Cox regression analysis identified three key predictors: age showed a positive log-linear effect (adjusted hazard ratio [HR] for 50% increase 1.2, 95% CI: 1.1-1.3, P=0.005), the serum concentration of thyrotropin showed a positive linear effect (adjusted HR for 1 mIU/L increase 1.3, 95% CI: 1.1-1.4, P<0.001) regardless the kind of disease incident, while the number of previous endocrine diseases showed a negative linear effect: the higher the number of diseases at baseline the lower the chance of developing further diseasess (adjusted HR for unit increase 0.5, 95% CI: 0.4-0.7, P<0.001). Age and thyrotropin had similar effect sizes across the categories of baseline diseases. The administration of levothyroxine as a covariate did not change the estimates. Although in DFX-treated TDT patients the risk of developing an endocrine complication is generally lower than the previously reported risk, there is considerable risk variation and the burden of these complications remains high. We developed a simple risk score chart enabling clinicians to estimate their patients' risk. Future research will look at increasing the amount of variation explained from our model and testing further clinical and laboratory predictors, including the assessment of direct endocrine magnetic resonance imaging.
Assuntos
Sobrecarga de Ferro , Talassemia , Talassemia beta , Benzoatos/efeitos adversos , Terapia por Quelação/efeitos adversos , Deferasirox/efeitos adversos , Seguimentos , Humanos , Quelantes de Ferro/efeitos adversos , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/etiologia , Medição de Risco , Fatores de Risco , Talassemia/complicações , Talassemia/epidemiologia , Talassemia/terapia , Triazóis/efeitos adversos , Talassemia beta/complicaçõesAssuntos
Transfusão de Sangue , Hospitalização , Admissão do Paciente , Talassemia/epidemiologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Comorbidade , Grupos Diagnósticos Relacionados , Feminino , Cardiopatias/epidemiologia , Cardiopatias/etiologia , Cardiopatias/prevenção & controle , Humanos , Lactente , Quelantes de Ferro/efeitos adversos , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Itália/epidemiologia , Masculino , Linfadenite Mesentérica/etiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Talassemia/complicações , Talassemia/terapia , Yersiniose/etiologia , Adulto JovemRESUMO
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.
Assuntos
Antioxidantes/isolamento & purificação , Aspergillus oryzae/química , Conservantes de Alimentos/isolamento & purificação , Quelantes de Ferro/isolamento & purificação , Modelos Químicos , Peptídeo Hidrolases/metabolismo , Peptídeos Cíclicos/isolamento & purificação , Animais , Antioxidantes/efeitos adversos , Antioxidantes/química , Antioxidantes/economia , Aspergillus oryzae/crescimento & desenvolvimento , Aspergillus oryzae/metabolismo , Fermentação , Conservantes de Alimentos/efeitos adversos , Conservantes de Alimentos/química , Conservantes de Alimentos/economia , Indústria de Processamento de Alimentos/economia , Proteínas Fúngicas/metabolismo , Temperatura Alta/efeitos adversos , Resíduos Industriais/análise , Resíduos Industriais/economia , Quelantes de Ferro/efeitos adversos , Quelantes de Ferro/química , Quelantes de Ferro/economia , Japão , Testes de Mutagenicidade , Oryza/química , Peptídeos Cíclicos/efeitos adversos , Peptídeos Cíclicos/química , Peptídeos Cíclicos/economia , Proteínas de Vegetais Comestíveis/química , Proteínas de Vegetais Comestíveis/economia , Proteínas de Vegetais Comestíveis/isolamento & purificação , Proteínas de Vegetais Comestíveis/metabolismo , Hidrolisados de Proteína/química , Hidrolisados de Proteína/economia , Hidrolisados de Proteína/isolamento & purificação , Hidrolisados de Proteína/metabolismo , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/metabolismo , Sementes/química , Testes de Toxicidade Aguda , Vinho/análise , Vinho/microbiologiaRESUMO
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.
Assuntos
Quelantes de Ferro/economia , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/economia , Piridonas/economia , Piridonas/uso terapêutico , Talassemia beta/complicações , Talassemia beta/economia , Análise Custo-Benefício/economia , Deferiprona , Custos de Medicamentos , Custos de Cuidados de Saúde , Humanos , Quelantes de Ferro/efeitos adversos , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/complicações , Modelos Econômicos , Piridonas/efeitos adversos , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Reino Unido , Talassemia beta/tratamento farmacológicoRESUMO
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.
Assuntos
Anemia Falciforme/tratamento farmacológico , Terapia por Quelação , Quelantes de Ferro/uso terapêutico , Custos e Análise de Custo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Quelantes de Ferro/efeitos adversos , Quelantes de Ferro/economia , Resultado do TratamentoRESUMO
We report the first prospective study evaluating the effects of deferasirox on liver iron concentration (LIC), labile plasma iron (LPI) and pharmacokinetics (PK) along with serum ferritin values in patients with IPSS Low- and Intermediate-1 risk myelodysplastic syndromes (MDS) and evidence of iron overload. Twenty-four heavily transfused MDS patients were enrolled in a planned 52 weeks of therapy. PK studies showed dose-proportional total drug exposure. Data demonstrated that deferasirox was well tolerated and effectively reduced LIC, LPI and serum ferritin in the iron-overloaded patients with MDS who completed 24 and 52 weeks of therapy despite ongoing receipt of red blood cell transfusions.
Assuntos
Benzoatos/administração & dosagem , Quelantes de Ferro/administração & dosagem , Sobrecarga de Ferro/tratamento farmacológico , Síndromes Mielodisplásicas/terapia , Triazóis/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Benzoatos/efeitos adversos , Deferasirox , Relação Dose-Resposta a Droga , Transfusão de Eritrócitos , Feminino , Ferritinas/sangue , Humanos , Ferro/sangue , Quelantes de Ferro/efeitos adversos , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/etiologia , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/complicações , Estudos Prospectivos , Triazóis/efeitos adversosAssuntos
Benzoatos/efeitos adversos , Benzoatos/economia , Terapia por Quelação/ética , Doenças Hematológicas/tratamento farmacológico , Quelantes de Ferro/efeitos adversos , Quelantes de Ferro/economia , Triazóis/efeitos adversos , Triazóis/economia , Benzoatos/uso terapêutico , Terapia por Quelação/efeitos adversos , Deferasirox , Deferiprona , Desferroxamina/uso terapêutico , Custos de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Humanos , Quelantes de Ferro/uso terapêutico , Piridonas/uso terapêutico , Medição de Risco , Sideróforos/uso terapêutico , Triazóis/uso terapêuticoAssuntos
Benzoatos/efeitos adversos , Terapia por Quelação , Quelantes de Ferro/efeitos adversos , Triazóis/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Benzoatos/economia , Benzoatos/uso terapêutico , Análise Custo-Benefício , Deferasirox , Deferiprona , Desferroxamina/economia , Desferroxamina/uso terapêutico , Custos de Medicamentos , Indústria Farmacêutica , Humanos , Quelantes de Ferro/economia , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/terapia , Piridonas/economia , Piridonas/uso terapêutico , Reação Transfusional , Triazóis/economia , Triazóis/uso terapêutico , Revelação da VerdadeRESUMO
There are major concerns regarding the toxicity, efficacy and costs of deferasirox in transfused iron loaded patients. Marketing policies resulted in its indiscriminate use and have overtaken safety issues. Renal, hepatic and pancytopenia fatal episodes have been reported. However, despite these fatalities it would appear that there is no regular monitoring of such toxicities or of effects such as the accumulation of toxic metals. The safety of some patients can also be compromised by the low efficacy of deferasirox in the removal of excess iron, especially from the heart, which in the long term can also result in an overall increase in morbidity and mortality. Safer, less costly and more effective treatments are available by using deferoxamine, deferiprone and their combination.
Assuntos
Benzoatos/administração & dosagem , Quelantes de Ferro/administração & dosagem , Sobrecarga de Ferro/tratamento farmacológico , Triazóis/administração & dosagem , Benzoatos/efeitos adversos , Benzoatos/economia , Deferasirox , Deferiprona , Quimioterapia Combinada , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Quelantes de Ferro/efeitos adversos , Quelantes de Ferro/economia , Sobrecarga de Ferro/mortalidade , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Piridonas/uso terapêutico , Reação Transfusional , Triazóis/efeitos adversos , Triazóis/economiaRESUMO
INTRODUCTION: This study of UK patients examines clinical, health-related quality of life (HRQOL) and economic outcomes associated with iron chelation therapy (ICT). Desferrioxamine (DFO) (Desferal; Novartis, Switzerland) and Deferiprone (Ferriprox; Apotex, Canada) are ICTs used to treat iron overload. DFO requires 8-to 12-hour infusions a minimum of five times per week. Deferiprone is administered in an oral daily regimen. Although pharmacologically efficacious, clinical effectiveness of ICT within the real-world setting is yet to be fully elucidated. METHODS: A naturalistic cohort study of 60 patients (beta-thalassaemia, n=40; sickle cell disease, n=14; myelodysplastic syndromes, n=6; 63% female) receiving ICT in four UK treatment centres was conducted. Serum ferritin level data were abstracted from medical charts. Compliance, HRQOL, satisfaction and resource utilisation data were collected from interviews. Maximum ICT costs were estimated using the resource utilisation data associated with DFO. RESULTS: Mean serum ferritin levels, generally, remained elevated despite ICT. Compliance was suboptimal and HRQOL scores were lower than population norms. The total estimated mean weighted annual per-patient cost of DFO treatment was approximately pound19,000. DFO-related equipment, DFO drug, and home healthcare were estimated to account for 43%, 19% and 24% of costs, respectively. Other more minor components of total annual costs were for in-patient infusions, ICT home delivery services and monitoring costs. CONCLUSION: Generally, patients are not achieving target serum ferritin thresholds despite chronic treatment for iron overload. ICT appears to negatively impact HRQOL; compliance with ICT is poor; and, in the case of DFO, treatment costs well exceed the cost of DFO alone. These results suggest that current ICT in the real-world setting is suboptimal with respect to various clinical, HRQOL and economic outcomes.
Assuntos
Terapia por Quelação , Desferroxamina/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Piridonas/uso terapêutico , Qualidade de Vida , Adolescente , Adulto , Terapia por Quelação/efeitos adversos , Terapia por Quelação/economia , Criança , Custos e Análise de Custo , Deferiprona , Desferroxamina/efeitos adversos , Desferroxamina/economia , Feminino , Ferritinas/sangue , Humanos , Quelantes de Ferro/efeitos adversos , Quelantes de Ferro/economia , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/economia , Masculino , Piridonas/efeitos adversos , Piridonas/economia , Adulto JovemRESUMO
New developments in the area of iron and other metal metabolism and toxicity and the effects and uses of chelators have been presented at the 16th International Conference on Chelation (ICOC), Limassol, Cyprus in October 2006. Marketing practices by pharmaceutical companies, contradictory policies by regulatory authorities and ineffective policies by health authorities deprive thousands of thalassemia and other transfused patients of life saving iron chelating drugs and of efficacious chelation treatments. Thousands of patients were using deferasirox (DFRA) worldwide a few months after the European Union (EU) authorities, and about 1 year after the Food and Drugs Administration (FDA), proceeded to its accelerated approval with no sufficient evidence that the drug was efficacious, especially for clearing excess cardiac iron, and also safe. Cases of fatal, acute, irreversible renal and liver failure, fatal agranulocytosis and other toxicities have recently been reported with DFRA. The FDA has not yet approved deferiprone (L1) depriving thousands of patients of potentially life saving treatment. The high cost of DFRA at 60 euros/g, L1 at 5.5 euros/g and deferoxamine (DFO) at 8.3 euros/g, diminishes the prospects of universal chelation therapy, especially for patients in developing countries. The safety and efficacy record of L1, DFO, and their combination in particular, appear to provide universal solutions in the treatment of transfusional iron overload, and also in reducing mortality because of their ability to clear rapidly and effectively excess cardiac iron.
Assuntos
Terapia por Quelação , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Talassemia/tratamento farmacológico , Benzoatos/efeitos adversos , Benzoatos/química , Benzoatos/economia , Benzoatos/uso terapêutico , Terapia por Quelação/economia , Terapia por Quelação/ética , Deferasirox , Deferiprona , Desferroxamina/química , Desferroxamina/economia , Desferroxamina/uso terapêutico , Aprovação de Drogas , Quimioterapia Combinada , Humanos , Ferro/metabolismo , Quelantes de Ferro/efeitos adversos , Quelantes de Ferro/química , Quelantes de Ferro/economia , Piridonas/química , Piridonas/economia , Piridonas/uso terapêutico , Medição de Risco , Sideróforos/química , Sideróforos/economia , Sideróforos/uso terapêutico , Talassemia/epidemiologia , Triazóis/efeitos adversos , Triazóis/química , Triazóis/economia , Triazóis/uso terapêuticoRESUMO
Dr. Nancy Olivieri has become an icon of research integrity for her insistence on publishing adverse data about a drug she was investigating. She has been celebrated world-wide as a hero of biomedical ethics for her bravery in disclosing potential dangers to research subjects, in the face of both drug company threats and coercive pressures from her hospital and university. Like so many other 'whistle-blowers' however, she now faces both personal vilification and disturbing accusations of scientific error. The case against Olivieri is assessed and found to be baseless.