Cost-utility of new film-coated tablet formulation of deferasirox vs deferoxamine among major beta-thalassemia patients in Iran.

OBJECTIVES: Thalassemia is a hereditary disease, which caused economic burden in developing countries. This study evaluated the cost utility of new formulation of deferasirox (Jadenu) vs deferoxamine (Desferal) among B-Thalassemia-major patients from payer perspective in Iran. METHODS: An economic-evaluation through Markov model was performed. A systematic review was conducted in order to evaluate the clinical effectiveness of comparators. Because of chelating therapy is weight-dependent, patients were assumed to be 2 years-old at initiation in first and 18 years-old in second scenario, and model was estimated lifetime costs and utilities. Costs were calculated to the Iran healthcare system through payer perspective and measured effectiveness using quality-adjusted life years (QALYs). One-way sensitivity analysis and budget impact analysis was also employed. RESULTS: The 381 studies were retrieved from systematic searching through databases. After eliminating duplicate and irrelevant studies, 2 studies selected for evaluating the effectiveness. Jadenu was associated with an incremental cost-effectiveness ratio (ICER) of 1470.6 and 2544.7 US$ vs Desferal in first and second scenario respectively. The estimated ICER for Jadenu compared to generic deferoxamine was 2837.0 and 6924.1 US$ for first and second scenario respectively. For all scenarios Jadenu is presumed as cost-effective option based on calculated ICER which was lower than 1 gross domestic product per capita in Iran. Sensitivity analysis showed that different parameters except discount rate and indirect cost did not have impact on results. Based on budget impact analysis the estimated cost for patients using Desferal (based on the market share of brand) was 44,021,478 US$ in 3 years vs 42,452,606 US$ in replacing 33% of brand market share with Jadenu. This replacement corresponded to the cost saving of almost 1,568,872 US$ for the payers in 3 years. The calculated cost of using generic deferoxamine in all patients was 68,948,392 US$. The increase in the cost of using Jadenu for 10% of all patients in this scenario would be 934,427 US$ (1.36%) US$ at the first year. CONCLUSIONS: Based on this analysis, film-coated deferasirox appeared to be cost-effective treatment in comparison with Desferal for managing child and adult chronic iron overload in B-thalassemia major patients of Iran.

Cost-Utility Analysis of Three Iron Chelators Used in Monotherapy for the Treatment of Chronic Iron Overload in ß-Thalassaemia Major Patients: An Italian Perspective.

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.

Management of the thalassemias.

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.

Long-term persistency and costs associated with the use of iron chelation therapies in the treatment of Sickle cell disease within Medicaid programs.

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.

Cost-utility analysis of oral deferasirox versus infusional deferoxamine in transfusion-dependent ß-thalassemia patients.

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.

Lifetime cost-utility analyses of deferasirox in beta-thalassaemia patients with chronic iron overload: a UK perspective.

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.

Iron-chelating therapies in a transfusion-dependent thalassaemia population in Thailand: a cost-effectiveness study.

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.

Cost effectiveness of deferasirox compared to desferrioxamine in the treatment of iron overload in lower-risk, transfusion-dependent myelodysplastic syndrome patients.

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.

[Epidemiological and economic aspects of chelating therapy in the therapeutic center of thalassemia in Morocco]. / Aspects épidémiologiques et économiques des traitements chélateurs au centre thérapeutique de la thalassémie au Maroc.

The study aims to give a general idea about the new experience of chelating drugs among beta-thalassemia patients. It is a declarative survey. It was done in the therapy center of Morocco. Statistics were done in the Laboratory of Biological Essays in Kenitra. All economic and pharmacological data were given by Novartis. Sample size was 89. The only treatment available now in the therapy center is deferiprone. 78% of patients attending the service regularly take deferiprone as treatment while 13% of them combine deferiprone and deferoxamine. Most of the patients take treatments regularly. Chelators have reduced mortality. Patients taking deferoxamine experienced injection site reactions. Most of ADR due to deferiprone were digestive. In conclusion, the main problem with chelators in Morocco is lack of accessibility to drugs (except for some patients insured or payant).

Iron chelation therapy in myelodysplastic syndromes.

PURPOSE: To understand how to appropriately recognize and manage iron overload with iron chelation therapy (ICT) in patients with myelodysplastic syndromes (MDS), evaluation of the role of different agents available for management of iron overload, including efficacy, safety, and economic considerations for transfusion-dependent patients with MDS, is provided. SUMMARY: Patients with MDS have a high incidence of anemia, which often requires treatment. Supportive care measures such as red blood cell transfusions and erythroid colony stimulating factors are mainstays of therapy. Use of long-term transfusion therapy has limitations in patients with MDS due to the risk of developing iron overload. Strategies to manage iron overload include phlebotomy and ICT with agents such as deferoxamine and deferasirox. Data evaluating pharmacologic therapy for treatment of iron overload in patients with MDS suggest timely intervention can mitigate the morbidity associated with this clinical syndrome. CONCLUSION: Development of practical management strategies to implement and optimize ICT using deferoxamine and deferasirox will be important to provide optimal care for transfusion-dependent patients with MDS.

Deferasirox for the treatment of iron overload associated with regular blood transfusions (transfusional haemosiderosis) in patients suffering with chronic anaemia: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of deferasirox for the treatment of iron overload associated with regular blood transfusions in patients with chronic anaemia such as beta-thalassaemia major (beta-TM) and sickle cell disease (SCD). DATA SOURCES: Electronic databases were searched up to March 2007. REVIEW METHODS: Methods followed accepted procedures for conducting and reporting systematic reviews and economic evaluations. RESULTS: A total of 14 randomised controlled trials (RCTs) involving a study population of 1480 (ranging from 13 to 586) met the inclusion criteria. There was a high degree of heterogeneity between trials in terms of trial design and outcome reporting. As such it was only possible to meta-analyse serum ferritin data from six trials making comparisons between deferiprone and DFO and combination therapy and DFO. Only one of the results was statistically significant, favouring combination therapy over DFO alone for serum ferritin at 12 months. How this translates into iron loading in organs such as the heart is unclear, nor was it possible to determine the long-term benefits of chelation therapy. Eight full economic evaluations (one full paper; seven abstracts) were included in the review. The results were generally consistent and appear to demonstrate the cost-effectiveness of deferasirox compared with DFO for the treatment of iron overload in a number of different patient populations and study locations. However, a number of assumptions and, in the case of the long-term studies, extrapolation from short-term RCT data were required, which render the results highly speculative at best. Because of the paucity of long-term data we developed a simple, short-term (1 year) model to assess the costs and benefits of deferasirox, deferiprone and DFO in patients with beta-TM and SCD from an NHS perspective. A number of assumptions were required to generate results and, as such, they should be interpreted as indicative rather than factual. Our model suggests that deferasirox may be a cost-effective strategy compared with DFO, at a cost per quality-adjusted life-year (QALY) below 30,000 pounds per year, for patients with beta-TM and SCD. However, this is highly dependent upon the age of the patient and the use and benefits of balloon infusers to administer DFO. Deferasirox compared with deferiprone is likely to be cost-effective only for young children. Furthermore, if deferiprone is proven to offer the same health benefits as deferasirox, the latter will not be cost-effective for any patient compared with deferiprone. CONCLUSIONS: In the short term there is little clinical difference between any of the three chelators in terms of removing iron from the blood and liver. Deferasirox may be cost-effective compared with DFO in patients with beta-TM and SCD, but it is unlikely to be cost-effective compared with deferiprone. Elucidating the long-term benefits of chelation therapy, including issues of adverse events and adherence, should be the primary focus for future research. Future work should aim for consistency and transparency in reporting study design and results to aid decision-making when making comparisons across trials.

A time-cost augmented economic evaluation of oral deferasirox versus infusional deferoxamine [corrected] for patients with iron overload in South Korea.

OBJECTIVES: This study aims to conduct an economic evaluation of oral deferasirox (DSX) compared with infusional deferoxamine (DFO) in patients with transfusional iron overload. METHODS: Depending on the methods for measuring time-cost and convenience associated with the mode of administration, either cost-utility analysis or cost-effectiveness analysis was undertaken. The difference in compliance rate between DSX and DFO was applied. RESULTS: Although the drug cost of DSX was US$124,070 higher than that of DFO (US$96,039 vs. US$220,199), all other costs were lower in patients with DSX than in patients with DFO. In the cost-utility analysis, DSX resulted in US$3197 savings with a gain of 2.63 quality-adjusted life-years per patient. The result of the cost-effectiveness analysis also showed that DSX dominated DFO. CONCLUSIONS: With a considerable improvement in convenience and injection time rather than efficacy, DSX is considered as a dominant therapy for patients with iron overload.

The costs of drugs used to treat myelodysplastic syndromes following National Comprehensive Cancer Network Guidelines.

Guidelines for management of patients with myelodysplastic syndromes (MDS) have been generated by the National Comprehensive Cancer Network (NCCN) Myelodysplastic Syndromes Panel. Because MDS is a heterogeneous spectrum of disorders, these patients have been categorized into prognostic subgroups, predominantly using the International Prognostic Scoring System (IPSS). Several drugs have been used to treat these patients, and their selection and sequential recommended use by the panel depend on disease characteristics and responses to treatment. Recombinant erythropoietin alfa and darbepoetin alfa have been the mainstay of therapy for treating anemia associated with MDS. The FDA has recently approved several other drugs for treating MDS, including azacytidine and decitabine for all stages of disease, lenalidomide for low-risk anemic patients with del(5q) chromosomal abnormality, and deferasirox for treating iron overload. For iron chelation, deferoxamine is also used occasionally. Treatment with immunosuppressive therapy (antithymocyte globulin and cyclosporin) has been therapeutically beneficial for a subset of younger patients with MDS. Because the financial cost of these therapies are substantial and have received only limited attention, this article evaluates the costs of specific drugs and their sequential use in the lower-risk IPSS (low and intermediate-1) subgroups based on the NCCN guidelines. Results estimate an average annual cost for potentially anemia-altering drugs of $63,577 per patient, ranging from $26,000 to $95,000, depending on the specific therapies. In patients for whom the therapies fail, annual costs for iron chelation plus red blood cell transfusions are estimated to average $41,412. The economic impact of drug therapy should be weighed against the patient's potential for improvement in clinical outcomes, quality of life, and transfusion requirements.

Iron chelation therapy: clinical effectiveness, economic burden and quality of life in patients with iron overload.

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.

Cost-utility analysis of deferasirox compared to standard therapy with desferrioxamine for patients requiring iron chelation therapy in the United Kingdom.

OBJECTIVE: The primary objective of the study was to evaluate the cost-utility of deferasirox (Exjade) compared to standard therapy using desferrioxamine (Desferal) for the control of iron overload in patients receiving frequent blood transfusions. The perspective adopted was that of the National Health Service in the UK. METHODS: Phase II/III clinical trials have shown deferasirox in the recommended doses of 20-30 mg/kg per day to have similar efficacy to desferrioxamine at equivalent doses in the control of chronic iron overload. The main difference between them is in the mode of administration. Desferrioxamine is administered parenterally as a slow subcutaneous infusion typically infused 8-12 hours a day for 5-7 days a week. In comparison, deferasirox provides 24 hour chelation via a once daily oral tablet dispersed in water or juice. An excel based economic model was developed to evaluate the annual healthcare costs and quality of life, or utility, benefits associated with differences in mode of administration, using beta-thalassaemia as the reference case. A community utility study using time trade-off methods was performed to determine utility outcomes associated with iron chelation therapy (ICT) mode of administration. RESULTS: In the reference case (patient mean weight 42 kg), deferasirox 'dominated' desferrioxamine, i.e. resulted in lower net costs and higher quality adjusted life years (QALYs). Drug dose and cost is patient weight related. Incremental cost per QALY gained was pound 7775 for patients with a mean weight of 62 kg. CONCLUSIONS: The cost-utility analysis did not take drug compliance into account. However, Deferasirox is cost-effective compared to standard iron chelation therapy with desferrioxamine, due to the cost and quality of life benefits derived from a simpler and more convenient oral mode of administration.

Ethical issues and risk/benefit assessment of iron chelation therapy: advances with deferiprone/deferoxamine combinations and concerns about the safety, efficacy and costs of deferasirox.

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.

Clinical and economic burden of infused iron chelation therapy in the United States.

BACKGROUND: Patients requiring chronic blood transfusions are at risk for iron overload, which, if not treated by iron chelation therapy (ICT), can create serious organ damage and reduce life expectancy. Current ICT requires burdensome 8- to 12-hour infusions five to seven times per week. STUDY DESIGN AND METHODS: A naturalistic study of the burden of infused ICT was conducted in four US centers. Data from the initial and most recent years of ICT were collected from medical charts of consenting thalassemia (n = 40) and sickle cell disease (n = 9) patients. Quality of life (QoL), treatment satisfaction, and ICT-related resource utilization data were also collected from a patient interview. RESULTS: Mean serum ferritin levels during the initial (2519 +/- 1382 ng/mL) and most recent (2741 +/- 2532 ng/mL) years remained unacceptably high and increased over time (306 +/- 2200 ng/mL; mean of 20+/- years of therapy). Within 30 days before interview, 55 percent of patients suffered at least one ICT-related adverse event; 76 percent missed at least one dose. QoL, measured by the SF-36, and treatment satisfaction appear compromised in this cohort. Although total annual costs of ICT were estimated at USD $30,000 to $35,000, drug accounted for only 50 to 60 percent of this amount. CONCLUSIONS: Infused ICT may not provide adequate effectiveness in the real world. High ferritin levels seem to be associated with ICT noncompliance, likely in relation to the bothersome mode of administration and side effects. The total cost of ICT appears to well exceed that of drug alone.

Current status of iron overload and chelation with deferasirox.

A large number of complications in thalassemia major are due mainly to iron overload. Deferoxamine in iron-overloaded patients has established that chelation therapy, when given at an adequate dose, reduces iron-related complications. Parenteral administration and the daily nuisance of an infusion pump hinder the optimal compliance. Deferiprone is moderately effective oral iron chelator. Arthralgia and cytopenias constitute the main side effects. Deferasirox is a new orally effective iron chelator which has been shown to be non-inferior to deferoxamine in clinical trials. Further clinical trials especially in Indian children will tell if it stands the test of time.

Erythrocytapheresis can reduce iron overload and prevent the need for chelation therapy in chronically transfused pediatric patients.

PURPOSE: This research was undertaken to determine the advantages, complications, costs, and efficacy of erythrocytapheresis in young pediatric patients who receive chronic erythrocyte transfusion therapy. PATIENTS AND METHODS: We retrospectively analyzed data for 10 children who received erythrocytapheresis for an average of 16 months. Erythrocytapheresis was compared to simple transfusion therapy with respect to annual blood unit exposure, occurrence of alloimmunization, and costs. Serum ferritin levels were compared before and after the period of erythrocytapheresis. RESULTS: Erythrocytapheresis was well tolerated, even in children as young as 5 years or as small as 20 kg. It required a greater annual unit exposure than simple transfusions, but did not increase alloimmunization. Ferritin levels decreased significantly in children receiving concurrent deferoxamine, and decreased or stabilized in those not on chelation therapy. Children started on erythrocytapheresis soon after stroke have not developed iron overload. Although the costs of erythrocytapheresis exceed that of simple transfusion, the substantial costs of deferoxamine therapy should be considered; one child on erythrocytapheresis has been able to discontinue chelation therapy following normalization of his ferritin level. CONCLUSION: Erythrocytapheresis is a safe and effective method for young patients receiving chronic erythrocyte transfusions. Erythrocytapheresis can reduce total iron burden and may obviate the need for expensive chelation therapy.