Comparison of Yearly Cost Related to Complications Between Deferasirox and Deferiprone Monotherapy in Thalassemia.

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.

Cost-effectiveness analysis of Manuka honey-Omega-3 combination treatments in treating oxidative stress of pediatric ß-thalassemia major.

OBJECTIVE: Oxidative stress represents a ruthless complication of ß-thalassemia that worsens the severity of that medical condition. There is no conclusive evidence on the best antioxidant used for that issue. Our earlier clinical study concluded that omega-3 and Manuka honey add-on to the conventional therapy had a potential therapeutic impact on reducing oxidative stress. However, there is no research evaluating their cost-effectiveness. This paper compares the cost-effectiveness of Omega-3 and Manuka honey supplementation to conventional therapy in treating oxidative stress among children with ß-thalassemia major. SUBJECTS AND METHODS: Cost-effectiveness evaluation of daily supplementation of Omega-3-Manuka honey and Manuka honey alone to the conventional therapy was performed. The economic evaluation was performed on data from a prospective 10-month randomized clinical trial. Fifty patients were recruited into the Omega-3-Manuka honey plus conventional therapy group, 50 patients were included in the Manuka honey alone plus conventional therapy group, and 50 patients receiving the conventional therapy alone served as a control group. Effectiveness measures from the randomized clinical trial were used to determine incremental effectiveness. Cost estimates were calculated from the healthcare payer's perspective. The analysis considered the improvement in oxidative stress biomarkers presented here as a percent change from baseline to determine the incremental effectiveness and cost for the treatment by both interventions. RESULTS: Adding Omega-3 or Manuka honey to conventional therapy was a more cost-effective add-on than conventional treatment alone. Omega-3-Manuka honey was more cost-effective than Manuka honey alone in treating oxidative stress in that condition. Oxidative stress biomarkers were significantly reduced with both experimental medications compared to the conventional therapy alone. CONCLUSIONS: The present study showed that using Manuka honey and Omega-3 as add-on treatments for oxidative stress in pediatric ß-thalassemia disease could have significant cost-saving and clinical improvement.

Drug Selection and Posology, Optimal Therapies and Risk/Benefit Assessment in Medicine: The Paradigm of Iron-Chelating Drugs.

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.

Major Thalassemia, Screening or Treatment: An Economic Evaluation Study in Iran.

BACKGROUND: Beta-thalassemia minor and thalassemia major are an autosomal recessive disease with hypochromic, microcytic anemia, and morbidities, Today, therapeutic advances have significantly improved the life expectancy of thalassemia major patients, but at the cost of financial toxicity. The present study aimed to investigate the possibility of increasing the funding for thalassemia screening programs and comparing the cost-effectiveness of screening for thalassemia in the treatment of the patients. METHODS: In this study, screening for thalassemia minor was compared with the treatment of thalassemia major patients. A decision tree model was used for analysis. A hospital database, supplemented with a review of published literature, was used to derive input parameters for the model. A lifetime study horizon was used and future costs and consequences were discounted at 3%. The approach of purchases of services was used to evaluate the screening test costs for patients with thalassemia major. Also, a bottom-up method was applied to estimate other screening and treatment costs. All the costs were calculated over one year. The number of gained quality-adjusted life years (QALYs) was calculated using the EQ-5D questionnaire in the evaluated patients. RESULTS: In this study, 26.97 births of patients with thalassemia major were prevented by screening techniques. On the other hand, total screening costs for patients with thalassemia major were estimated equal to US$ 879879, while the costs of preventing the birth of each thalassaemia major patient was US$ 32 624 by screening techniques. In comparison, the cost of managing a patient with thalassemia major is about US$ 136 532 per year. The life time QALYs for this is 11.8 QALYs. Results are presented using a societal perspective. Incremental cost per QALY gained with screening as compared with managing thalassaemia major was US$ 11 571. CONCLUSION: Screening is a long-term value for money intervention that is highly cost effective and its long-term clinical and economic benefits outweigh those of managing thalassaemia major patients.

Drug utilization study and cost analysis of adult ß-thalassemia major patient therapy at Dr. Soetomo General Hospital Surabaya.

OBJECTIVES: The main therapy of ß-thalassemia major are blood transfusion and iron chelation drugs. However, those therapies also have some adverse effects and problems such as iron overload, transfusion reactions, nutritional deficiencies, and patient compliance problems. Those arising problems also have an impact on therapy cost. Hence, this study was designed to analyze drug utilization study and cost of therapy in ß-thalassemia major adult patients at Dr. Soetomo General Hospital Surabaya. METHODS: This research was conducted in descriptive observational-retrospective design using secondary data obtained from patient's medical records and billing registrations from January 1-December 31, 2019. RESULTS: There were 18 patients out of 233 patients that were analyzed. Deferasirox was the most administered drug with doses between 500 mg/day-1,500 mg/day while deferiprone was ranged between 1,500 and 4,500 mg/day. Patients also received transfusion reaction drugs with dexamethasone injection 5 mg/ml which was administered the most. The most administered supplement was folic acid 1 mg. Patients had an increase in serum ferritin due to low compliance. Deferasirox had the most adherence number of patients with decrease of serum ferritin. The two highest costs of direct medical components were top-up medicines and consumable medical supplies. Overall, the hospital gained profit from national health insurance claims. CONCLUSIONS: The most administered chelating agent was deferasirox. Deferasirox also had the most adherence number of patients with decreased number of serum ferritin. However, deferasirox also yielded the highest cost. Yet, overall, the hospital gained profit from national health insurance claims.

Population Pharmacokinetics and Exposure-Response Relationship of Luspatercept, an Erythroid Maturation Agent, in Anemic Patients With ß-Thalassemia.

ß-Thalassemia is an inherited blood disorder resulting from defects in hemoglobin production, leading to premature death of red blood cells (RBCs) or their precursors. Patients with transfusion-dependent ß-thalassemia often need lifelong regular RBC transfusions to maintain adequate hemoglobin levels. Frequent transfusions may lead to iron overload and organ damage. Thus, there is a large unmet need for alternative therapies. Luspatercept, a first-in-class erythroid maturation agent, is the first approved therapy in the United States for the treatment of anemia in adult patients with ß-thalassemia who require regular RBC transfusions. The population pharmacokinetics and exposure-response relationship of luspatercept were evaluated in 285 patients with ß-thalassemia. Luspatercept displayed linear and time-invariant pharmacokinetics when administered subcutaneously once every 3 weeks. Body weight was the only clinically relevant covariate of luspatercept clearance, favoring weight-based dosing. Magnitude and frequency of hemoglobin increase, if not influenced by RBC transfusions, was positively correlated with luspatercept area under the serum concentration-time curve (AUC), 0.2-1.25 mg/kg, whereas a significant reduction in RBC units transfused was observed in frequently transfused patients. The probability of achieving ≥33% or ≥50% reduction in RBC transfusion burden was similar across the time-averaged AUC (0.6-1.25 mg/kg), with the 1 mg/kg starting dose sufficient for most early responders (71%-80%). Increasing luspatercept AUC (0.2-1.25 mg/kg) did not increase incidence or severity of treatment-emergent adverse events. These results provide a positive benefit-risk profile for the recommended luspatercept doses (1-1.25 mg/kg) in treating adult patients with ß-thalassemia who require regular RBC transfusions.

Incorporating a clinical oncology pharmacist into an ambulatory care pharmacy in pediatric hematology-oncology and transplant clinic: Assessment and significance.

BACKGROUND: Beta thalassemia patients, post-bone marrow transplant, and leukemia patients require long term therapy with an intense care follow-up especially for pediatric hematology-oncology origin. Emergence of side effects and noncompliance to therapy lead to reduced efficacy of medicines resulting in relapse of diseases. There is an increasing fact to support the incorporation of a pharmacist into clinical team due to their distinctive skills. Clinical oncology pharmacist with experience and specialized training in hematological cancers and bone marrow transplantation (BMT) patient care has in-depth knowledge and skills of chemotherapy regimens including drug information, monitoring parameters of cancer treatment, dose adjustment, drug-drug interactions, adverse effects, and patient counseling skills. AIM AND OBJECTIVES: The main objective of our study was to assess the significance of incorporation of clinical oncology pharmacist in ambulatory care in pediatric hematology-oncology and transplant clinic. MATERIAL AND METHOD: This study was conducted at National Institute of Blood Diseases and Bone Marrow Transplantation hospital with duration of five months from 17 March 2019 to 16 July 2019. In this study the clinical oncology pharmacist was made available at ambulatory clinic of hematology-oncology and transplantation. The activities performed by a clinical oncology pharmacist were observed by resident BMT clinical pharmacist during the visits of patients and their families in a clinic. The BMT pharmacist is a clinical oncology pharmacist with experience and specialized training in hematological cancers and BMT patient care. Only pediatrics patients with beta thalassemia major and those who were on chemotherapy treatment and post-transplant patient were included in this study. RESULTS: During the five months' tenure, there were 1820 pediatric patients' visits in total. The clinical oncology pharmacist performed 980 direct patient interviews and documented 1665 pharmacist interventions. The majority of the documented clinical oncology pharmacist interventions were review of medication histories (n: 404, 24%) and "deferiprone" dose adjustments (n:400, 24%). Genomic profiling interventions were also among the commonly reported activities by the clinical oncology pharmacist. For beta thalassemia patients undergoing hydroxyurea therapy, the genomic profiling was performed to assess whether the hydroxyurea treatment is clinically effective or not (n:396, 23%). CONCLUSION: The involvement of clinical oncology pharmacist into a specialized outpatient clinic of hematology-oncology and transplant clinic plays an integral role in minimizing the adverse effect and reduction in readmission into the hospital. This is new expansion of pharmacist's role especially in underdeveloped country, considering the relevant clinical participation of clinical oncology pharmacist into specialized clinic revealing through optimized therapy and future prospect of clinical oncology pharmacist in pediatric hematology.

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.

Noninvasive assessment and risk factors of liver fibrosis in patients with thalassemia major using shear wave elastography.

OBJECTIVES: This study aimed to estimate the prevalence of liver fibrosis and assess the risk factors for developing significant liver fibrosis in patients with Thalassemia Major (TM). METHODS: All patients with TM over the age of 10 years were included in the study. RESULTS: A total of 94 eligible patients underwent 2-D SWE. The median age was 26.7 years. The median of the average 5-year serum ferritin (5yrSF) and liver iron concentration (LIC) assessed by MRI T2* were 1326 µg/L and 6.7 mg/g dw, respectively. Hepatitis C and hepatitis B core antibodies were positive in 38% and 1% of the patients respectively. The proportion of patients with significant fibrosis was 60%. Male gender increased the risk of significant fibrosis (Odds ratio of 0.4; p = .0373). Additionally, the 5yrSF (p = .00661), the LIC (p = .0225) and the lowest LIC of the previous 5 years (p = .0211) were significant. In the multivariable logistic regression model, only 5yrSF (p = .0035) and gender (p = .00984) remained significant. CONCLUSIONS: The risk of liver fibrosis is associated with iron overload and gender in patients with TM.

Assessment of Serum Folic Acid and Homocysteine in Thalassemia Major Patients Before and After Folic Acid Supplement Cessation.

BACKGROUND: Thalassemic patients have ineffective erythropoiesis. In recent treatment protocols, there are little data on folic acid supplementation for patients with thalassemia because it is supposed that regular blood transfusions prevent bone marrow hyperfunctioning. OBJECTIVE: Investigators aimed to assess serum folic acid and homocysteine (Hcy) in thalassemia major patients before and after folic acid supplement cessation. PATIENTS AND METHODS: This study was a before-after controlled clinical trial conducted in 17th Shahrivar Hospital, Rasht, North of Iran, during May to October 2016. The patients enrolled in this study had thalassemia major on regular blood transfusion and older than 2 years of age. They had at least a 6-month history of folic acid supplement consumption before enrollment in the study (1 mg/daily). Complete blood count, serum folic acid, and serum Hcy were measured before discontinuation of folic acid supplement. Then, patients did not receive folic acid for a month and after 1 month of folic acid cessation, the measurements were repeated. All data were entered in SPSS version 20.0 and analyzed. RESULTS: Among the 40 patients in this study, 25 (62.5%) were female. The mean age of the participants was 21.39±11.17 years old. The mean of body mass index was 21.38±3.32 kg/m. Most of the participants had used folic acid supplement >5 years (29, 72.5%). The serum Hcy level was significantly increased (5.24±2.35 vs. 5.93±2.56; P=0.008) and serum folic acid level was decreased significantly (14.74±4.20 vs. 8.80±4.16; P<0.0001) from baseline. CONCLUSIONS: Cessation of folic acid supplementations in beta thalassemia major patients can lead to a significant decrease in serum folic acid and increase in Hcy levels. According to our findings and efficacy of folic acid in patients with beta thalassemia major, it is recommended to use the supplementation in all patients.

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.

MRI guided iron assessment and oral chelator use improve iron status in thalassemia major patients.

Oral iron chelators and magnetic resonance imaging (MRI) assessment of heart and liver iron burden have become widely available since the mid 2000s, allowing for improved patient compliance with chelation and noninvasive monitoring of iron levels for titration of therapy. We evaluated the impact of these changes in our center for patients with thalassemia major and transfusional iron overload. This single center, retrospective observational study covered the period from 2005 through 2012. Liver iron content (LIC) was estimated both by a T2* method and by R2 (Ferriscan® ) technique. Cardiac iron was assessed as cT2*. Forty-two patients (55% male) with transfused thalassemia and at least two MRIs were included (median age at first MRI, 17.5 y). Over a mean follow-up period of 5.2 ± 1.9 y, 190 MRIs were performed (median 4.5 per patient). Comparing baseline to last MRI, 63% of patients remained within target ranges for cT2* and LIC, and 13% improved from high values to the target range. Both the median LIC and cT2* (cR2* = 1000/cT2*) status improved over time: LIC 7.3 to 4.5 mg/g dry weight, P = 0.0004; cR2* 33.4 to 28.3 Hz, P = 0.01. Individual responses varied widely. Two patients died of heart failure during the study period. Annual MRI iron assessments and availability of oral chelators both facilitate changes in chelation dose and strategies to optimize care.

Cost-utility analysis of deferiprone for the treatment of ß-thalassaemia patients with chronic iron overload: a UK perspective.

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.

Comparative assessment of deferiprone and deferasirox in thalassemia major patients in the first two decades-single centre experience.

Iron overload is mainly responsible for the morbidity and mortality in patients with beta thalassemia major (TM). Our aim was to compare treatment outcomes with oral iron chelators, deferiprone (DFP), and deferasirox (DFX) in the first two decades on therapy. Seventy patients with TM (mean age ± SD, 7.9 ± 4.2; range 1.5-17 years) attending the pediatric day care unit for regular transfusional support were enrolled in this cross-sectional cohort study. The patients were treated either with DFP at the dose of 75-100 mg/kg/d in three divided doses after food or DFX at the dose of 25-40 mg/kg/d as single dose before food. Mean serum ferritin (±SD) was lower in patients below 10 years (n = 44) at 1283 (±600) ng/mL when compared with patients ≥10 years (n = 19) at 1546 (±589) ng/mL. There was no significant difference in mean serum ferritin (±SD) level in patients receiving DFP (1360 ± 589) versus DFX (1260 ± 641) in this cohort, P > 0.05. 67% of the patients had Vitamin D deficiency (<50 umol/L). Our results show comparable efficacy of DFP and DFX with regards to iron chelation as estimated by serial serum ferritin levels; however, MRI T2* values were higher in the DFP-treated patients compared to DFX treatment.

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.

A new tool for the assessment of satisfaction with iron chelation therapy (ICT-Sat) for patients with ß-thalassemia major.

BACKGROUND: High satisfaction with iron chelation is a major determinant for adherence to ICT in beta-thalassaemia major (ß-TM) patients. In this study, a new tool to assess different domains of satisfaction for available forms of ICT was developed and validated. The impact of patients' satisfaction with ICT has been tested. METHODS: Items were generated via focus groups and a preliminary version with 24 items (ICT-Sat) with an additional item for treatment preference and a knowledge questionnaire (KQ) was developed. 170 ß-TM patients from three Thalassaemia centers in Egypt, aged 2-32 years received three questionnaires to fill in; the new ICT-Sat, a KQ, and a previously validated tool for satisfaction with ICT (SICT) and retested 4-6 weeks later to ensure re-test reliability. Type of chelation, drug related adverse events, compliance with ICT, and serum ferritin level (SF) during the year prior to the study as well as available cardiac T2*data were recorded. RESULTS: One hundred and fifty two ß-TM patients completed all questionnaires; median age was 12 years. The final 15 remaining ICT-Sat items, yielding to four domain scores, explained 70.6% of the total variance. The "perceived effectiveness" and "fear and worries" domains of the ICT-Sat correlated significantly with the domains "perceived effectiveness" and "acceptance" of the SICT. Patients treated with oral ICT were more satisfied with perceived effectiveness, and their side effects. CONCLUSIONS: A new clinically based ICT-Sat tool was developed and revealed good psychometric characteristics. Adherence to ICT was better correlated with "perceived effectiveness" and SF level.

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.

Pharmacoeconomic considerations in treating iron overload in patients with ß-thalassaemia, sickle cell disease and myelodysplastic syndromes in the US: a literature review.

Patients with ß-thalassaemia, sickle cell disease (SCD) and myelodysplastic syndromes (MDS) require chronic blood transfusions, which can lead to iron overload and substantial morbidity and mortality. To reduce the excess iron and its deleterious effects, available iron chelation therapy (ICT) in the US includes oral deferasirox or infusional deferoxamine (DFO). The aim of this study was to review and synthesize the available pharmacoeconomic evidence on ICT in patients with ß-thalassaemia, SCD and MDS in the US. We systematically identified and reviewed pharmacoeconomic studies of ICT in patients with ß-thalassaemia, SCD and MDS that either were published in MEDLINE-indexed, English-language journals from 1999 to 2009, or appeared in medical society websites and scientific meeting abstracts. We assessed available cost-of-illness, cost-of-treatment, cost-consequence, cost-effectiveness, utility and patient-satisfaction studies. The majority of the 20 identified studies assessed cost of treatment, mainly focusing on acquisition and administration costs of ICTs. Gaps in the published literature include current data on direct medical costs for patients with MDS, direct medical costs associated with complications of iron overload, direct non-medical costs, indirect costs and patient utilities. Different underlying model assumptions, methodologies and comparators were found in the cost-effectiveness studies, which yielded a broad range of incremental cost-effectiveness ratios for different ICTs. Comprehensive cost-of-illness studies are needed to address data gaps in the published literature regarding the economic burden of iron overload. Comparative-effectiveness studies that evaluate clinical, economic and patient-reported outcomes would help the medical community to better understand the value of different ICTs.