Cost-minimization analysis comparing eltrombopag vs romiplostim for adults with chronic immune thrombocytopenia.

BACKGROUND: Promacta (eltrombopag; EPAG) and Nplate (romiplostim; ROMI) have not been compared in head-to-head trials for treatment of chronic immune thrombocytopenia (cITP); however, indirect treatment comparisons have indicated similar efficacy and safety outcomes, and the drugs are generally accepted as therapeutic alternatives. OBJECTIVE: To determine which of the 2 therapies would result in the lowest overall cost from a US health plan perspective, under the assumption of equivalent clinical efficacy and safety. METHODS: A cost-minimization model was developed in Microsoft Excel. The model incorporated only costs that differ between the treatments, including drug acquisition, administration, and monitoring costs, over a 52-week horizon. Average dosing for EPAG and ROMI was taken from the long-term EXTEND trial and from a published metaanalysis of 14 clinical trials, respectively. ROMI is injectable and EPAG is oral, so only ROMI had administration costs. The model assumed patients used 25 mg EPAG tablets and the 250 µg vial size of ROMI. ROMI wastage was included in drug acquisition costs by rounding up average dose to the nearest whole vial. Monitoring requirements were determined from US prescribing information, with platelet monitoring assumed equal, and hepatic panel testing every 4 weeks for EPAG. The model was adjustable to commercial, Medicare, and Medicaid plan perspectives, with optional inclusion of drug wastage, monitoring, or administration costs. RESULTS: The base case used a commercial plan perspective, with average dosing of 51.5 mg/day for EPAG and 4.20 µg/kg/week for ROMI. The analysis found a cost difference per treated patient of $64,770 in favor of EPAG on an annual basis. Breakdown by unique costs for EPAG included drug-acquisition cost of $123,135 and monitoring cost of $705. Breakdown by unique costs for ROMI included drug-acquisition cost of $183,234, with wastage of $63,179 and administration cost of $5,377. Based on a hypothetical commercial plan with 1 million members and an estimated 11 patients with cITP receiving ROMI, potential annual savings for switching all patients from ROMI to EPAG is $712,473 or $0.06 per member per month. EPAG remained the less costly option for all plan types and assumptions. A sensitivity analysis found that the result was most sensitive to drug pricing and wastage inputs. CONCLUSIONS: Because of lower drug-acquisition costs (including drug wastage) and administration costs, treatment of cITP with EPAG is associated with a lower net cost per patient than ROMI. DISCLOSURES: This study was funded by Novartis Pharmaceuticals Corporation. Proudman, Lucas, and Nellesen are employees of Analysis Group, Inc., which received funding from Novartis Pharmaceuticals Corporation to conduct this study. Patwardhan was employed by Novartis Pharmaceuticals Corporation at the time of this study; Allen is an employee of Novartis. This research was presented as an e-poster at the AMCP 2020 Virtual, April 2020.

The Cost-effectiveness of Eltrombopag for the Treatment of Immune Thrombocytopenia in the United States.

PURPOSE: Eltrombopag was evaluated as a second-line treatment for adult chronic immune thrombocytopenia (ITP) in the 2006 Phase III RAISE (Eltrombopag for Management of Chronic Immune Thrombocytopenia) randomized, placebo-controlled trial. More than 80% of patients reached satisfactory platelet counts within 2 weeks. However, the economic value of eltrombopag as a second-line treatment for ITP remains to be formally assessed. This study aimed to estimate the cost-effectiveness of treating ITP with a comparable thrombopoietin receptor agonist (eltrombopag vs romiplostim). METHODS: A Markov model was implemented over a lifetime time horizon to estimate the benefits and costs of each treatment. The model featured 3 health states based on current guidelines: (1) on treatment; (2) treatment failure/discontinuation; and (3) mortality. In line with therapeutic goals in ITP, model patients could experience 3 events: no bleeding, mild/moderate bleeding, or severe bleeding. Data on eltrombopag use were obtained from an open-label extension of previous Phase II/III trials, including RAISE. Romiplostim data were obtained from Phase III trials and an extension study. Lifetime overall survival was extrapolated by using treatment-specific mortality rates derived from severe bleeding and natural mortality rates. The costs of drugs, routine care, bleeding episodes, adverse events, and mortality were represented in the model. FINDINGS: Eltrombopag-treated patients gained 17.58 life years and 14.68 quality-adjusted life years, whereas romiplostim-treated patients gained 17.52 life years and 14.67 quality-adjusted life years. The total lifetime cost of eltrombopag treatment was estimated at $1.58 million versus $2.13 million for romiplostim. Sensitivity analyses supported base case findings. Deterministic sensitivity analysis predicted the greatest sensitivity to the rates of severe bleeding, discontinuation, and natural mortality. Probabilistic sensitivity analysis showed that eltrombopag would be an efficient use of resources at a $50,000 threshold in 52.8% of cases. In all probabilistic iterations, the total cost of eltrombopag treatment was lower than with romiplostim, primarily because of lower drug costs. IMPLICATIONS: Clinical data were applied in an economic analysis, and eltrombopag exhibited economic dominance compared with romiplostim, driven largely by the reduced costs of primary therapy. This model was limited by a lack of specific patient-level data and robust data on the duration of secondary therapy, as well as by the fact that utilization values are likely conservative estimates for routine care use.

Healthcare resource use and direct costs in severe aplastic anemia (SAA) patients before and after treatment with eltrombopag.

Purpose: This study evaluated healthcare resource utilization (HCRU), and direct costs among severe aplastic anemia (SAA) patients treated with eltrombopag (EPAG) using US claims data.Methods: This retrospective, real-world claims database study identified SAA patients aged ≥2 years treated with EPAG who initiated any SAA treatment between 1 July 2014 and 31 December 2017 (identification period) using the Truven MarketScan databases. A subset of 82 patients treated with EPAG during the identification period were evaluated for all-cause and SAA-related HCRU and direct costs as well as blood transfusion 1 month before EPAG initiation (baseline) and at Month 6 after EPAG initiation (follow-up period).Results: The average patient age was 50.8 (SD = 20.6) years old, predominantly female (n = 43, 52.4%), and had a mean CCI at baseline of 1.1 (SD = 1.7). Hospitalizations, and ER, office, and outpatient visits were significantly lower at Month 6 after EPAG initiation compared with 1 month before EPAG initiation (p < .05 for all four all-cause HCRU and SAA-related hospitalizations). An almost two-fold decrease in reliance on biweekly blood transfusions was observed: 1.0 at weeks 1-2 to 0.5 at Month 6 after EPAG initiation. Although prescription costs (mean [SD]) were significantly higher at Month 6 after EPAG initiation compared with 1 month before EPAG initiation (difference of $11,045 USD [SD = $18,801]), these increases were offset by savings in direct costs. Overall, a mean reduction in total all-cause costs of $29,391 USD [SD = $137,770] was reported at Month 6 after EPAG initiation due to substantial reductions in hospitalization ($40,060 USD [SD = $123,198]) and outpatient visits ($2,043 USD [SD = $25,264]).Conclusion: All-cause and SAA-related HCRU were reduced following EPAG treatment. Prescription costs were higher following treatment; however, these costs were generally offset by reductions in direct costs. These results provide real-world evidence around the role of EPAG in SAA treatment.

Cost per response analysis of strategies for chronic immune thrombocytopenia.

OBJECTIVES: This analysis estimated the cost per response and the incremental cost per additional responder of romplostim, eltrombopag, and the "watch-and-rescue" (monitoring until rescue therapies are required) strategy in adults with chronic immune thrombocytopenia (ITP). STUDY DESIGN: The decision tree is designed to estimate the total cost per response for romiplostim, eltrombopag, and watch and rescue over a 24-week time horizon; cost-effectiveness was evaluated in terms of incremental cost per additional responder. METHODS: Model inputs including response rates, bleeding-related episode (BRE) rates, and costs were estimated from registrational trial data, an independent Bayesian indirect comparison, database analyses, and peer-reviewed publications. Costs were applied to the proportions of patients with treatment response and nonresponse (based on platelet count). The total cost per response and the incremental cost per additional responder for each treatment were calculated. Sensitivity analyses and alternative analyses were performed. RESULTS: With higher total costs and greater treatment efficacy, romiplostim and eltrombopag had a lower 24-week cost per response and a lower average number of BREs than watch and rescue. Eltrombopag was weakly dominated by romiplostim. The incremental cost-effectiveness ratio of romiplostim versus watch and rescue was $46,000 per additional responder. The model results are most sensitive to response rates of romiplostim and watch and rescue and the BRE rate for splenectomized nonresponders. Alternative analyses results were similar to the base case. CONCLUSIONS: In adults with chronic ITP, romiplostim represents an efficient way to achieve response, with lower costs per response than eltrombopag; both romiplostim and eltrombopag had lower costs per response than watch and rescue.

A decision framework for treating chronic immune thrombocytopenia with thrombopoietin receptor agonists.

Aim: Eltrombopag and romiplostim are comparable second-line therapies in chronic immune thrombocytopenia. Treatment decisions are made in different contexts. A framework was created to outline decision pathways for physicians and payers. Materials & methods: The costs of drugs, administration, routine care, bleeding, other adverse events and mortality were included in the year-long calculation of total costs from a US private payer perspective. Treatment parameters and outcome data were obtained from relevant clinical trials. Results: The total cost per year, per patient of eltrombopag was US$51,000 versus US$76,000 for romiplostim. Drug costs and costs associated with bleeding-related events were the main drivers of cost difference. Conclusion: This framework facilitates decision-making in the management of chronic immune thrombocytopenia with eltrombopag and romiplostim.

Comparative treatment-related adverse event cost burden in immune thrombocytopenic purpura.

AIMS: Real-world evidence on the safety profile and costs associated with immune thrombocytopenic purpura (ITP) treatment in adults is lacking. This study quantifies and compares adverse event (AE) crude rates and costs associated with ITP treatments as found in claims data. MATERIALS AND METHODS: A retrospective claims-based analysis was conducted using IMS Pharmetrics Plus database. Included patients were ≥18 years old, with a diagnosis of ITP (2007-2012); an ITP-related claim for anti-D, intravenous immunoglobulin (IVIG), rituximab, romiplostim, or eltrombopag; and 1-year continuous enrollment (3-years for rituximab) during follow-up. AEs and event costs were identified during active treatment, defined from the first claim of each drug to a pre-defined treatment gap or end of study period. Descriptive statistics were reported with Wilcoxon rank-sum significance tests. RESULTS: A total of 2,518 patients were identified (mean age = 50.8 (±16.3 years); 55.8% male). Of all patients, 22.8% experienced any AE. Significantly fewer anti-D patients had any AE (13.8% vs IVIG: 21.1%, rituximab: 29.4%, romiplostim: 28.1%, eltrombopag: 22.4%). Nausea/vomiting and arthralgia/musculoskeletal pain were most common across treatments, and hemolytic events did not differ significantly across treatments. Most costly AEs were urinary tract infection, aseptic meningitis, and fever ($5000+/case); headache, nasal congestion, and hemolytic event were $4,000-5,000/case. Cost per AE did not differ by treatment. LIMITATIONS AND CONCLUSIONS: Although lower than trial-based AE rates, claims for ITP treatment-related AEs are common, with higher numbers for rituximab and lower numbers for anti-D. This disparity suggests a possible differential cost burden overall that future analysis should explore.

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.

Cost-Effectiveness of Eltrombopag versus Romiplostim for the Treatment of Chronic Immune Thrombocytopenia in England and Wales.

OBJECTIVES: To evaluate the cost-effectiveness of eltrombopag compared with romiplostim to be used in the treatment of chronic immune thrombocytopenia in patients in England and Wales who are splenectomized or ineligible for splenectomy and are refractory to other treatments. METHODS: A Markov cohort model in which patients were administered a sequence of treatments was used to predict long-term outcomes associated with each treatment. The model was informed by data from the eltrombopag clinical trial program and the available literature. The analysis was conducted from the perspective of the UK National Health Service, and a lifetime time horizon was used. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Eltrombopag dominated romiplostim (i.e., eltrombopag was as effective as but less costly than romiplostim) in both splenectomized and nonsplenectomized patients, assuming a class effect for the two treatments. Eltrombopag also dominated romiplostim in most deterministic sensitivity analyses with the exception of when indirect efficacy estimates were incorporated into the model. In this analysis, eltrombopag no longer dominated romiplostim but remained cost-effective versus romiplostim at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. Probabilistic sensitivity analysis demonstrated that there was a 99% and 92% chance of eltrombopag being cost-effective at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year in splenectomized and nonsplenectomized patients, respectively. CONCLUSIONS: Results of this study demonstrate that eltrombopag is cost-effective when compared with romiplostim to be used in the treatment of chronic immune thrombocytopenia, representing good value for the UK National Health Service.

Efficacy, acceptability and cost effectiveness of four therapeutic agents for treatment of scabies.

The aim of this study is to evaluate four drug regimens for treatment of scabies as regard their efficacy, acceptability and cost effectiveness. Two hundred cases with ordinary scabies were randomized into four groups. First group received ivermectin 200 µg/kg body weight single oral dose, repeated after one week. The second received benzyl benzoate 20% cream. The third received permethrin 2.5%-5% lotion, whereas the fourth group received 5-10% sulfur ointment. Topical treatments were applied for five consecutive nights. Patients were followed up for two weeks for cure rate and adverse effects. At the end of the study, permethrin provided a significant efficacy of 88% and acceptability in 100% of cases, but had higher cost to treat one case (20.25 LE). Ivermectin provided efficacy and acceptability rates of 84% and 96%, respectively, and had a cheaper cost (9.5 LE). Benzyl benzoate provided 80% for both rates and was the cheapest drug. Sulfur ointment provided the least rates, and it was the most expensive. Treatment choice will depend on the age, the general condition of cases, patient compliance to topical treatment and his ability to stick to its roles, and the economic condition of the patient.

Economic assessment of eltrombopag in the treatment of thrombocytopenia.

OBJECTIVE: This study assesses the cost-effectiveness of eltrombopag in the treatment of hepatitis C virus (HCV)-related thrombocytopenia. METHODS: A Markov model was constructed on the basis of the clinical trials ENABLE 1 and ENABLE 2. Three alternatives were considered: scenario 1; treatment with eltrombopag in both the enabling phase and during antiviral therapy, as in the ENABLE trial design; scenario 2; no eltrombopag treatment and no antiviral therapy; scenario 3; no eltrombopag treatment and subsequent administration of a reduced dose of peg-IFN. RESULTS: Base case results demonstrate that scenario 1 is associated with a cost per QALY of €30,020.94 in comparison with scenario 2. The incremental cost-effectiveness ratio reaches a value of €32,752.44 per QALY when scenario 1 is compared with scenario 3. CONCLUSION: The use of eltrombopag in HCV patients with thrombocytopenia is cost-effective as it leads to a reduction in disease progression and thus a drop in the number of patients with advanced liver disease.

Review of ongoing initiatives to improve prescribing efficiency in China; angiotensin receptor blockers as a case history.

INTRODUCTION: Pharmaceutical expenditure is rising by 16% per annum in China and is now 46% of total expenditure. Initiatives to moderate growth include drug pricing regulations and encouraging international non-proprietary name prescribing. However, there is no monitoring of physician prescribing quality and perverse incentives. OBJECTIVES: Assess changes in angiotensin receptor blocker (ARB) utilization and expenditure as more generics become available; compare findings to Europe. METHODOLOGY: Observational retrospective study of ARB utilization and expenditure between 2006 and 2012 in the largest hospital in Chongqing district. RESULTS: Variable and low use of generics versus originators with a maximum of 31% among single ARBs. Similar for fixed dose combinations. Prices typically reduced over time, greatest for generic telmisartan (-54%), mirroring price reductions in some European countries. However, no preferential increase in prescribing of lower cost generics. Accumulated savings of 33 million CNY for this large provider if they adopted European practices. CONCLUSION: Considerable opportunities to improve prescribing efficiency in China.

Cost effectiveness of romiplostim for the treatment of chronic immune thrombocytopenia in Ireland.

BACKGROUND: Romiplostim, a thrombopoietin receptor agonist (TPOra), is a second-line medical treatment option for adults with chronic immune thrombocytopenia (ITP). Clinical trials have shown that romiplostim increases platelet counts, while reducing the risk of bleeding and, in turn, the need for costly rescue medications. AIMS: The objective of this study was to assess the cost effectiveness of romiplostim in the treatment of adult ITP in Ireland, in comparison with eltrombopag and the medical standard of care (SoC). METHODS: A lifetime treatment-sequence cost-utility Markov model with embedded decision tree was developed from an Irish healthcare perspective to compare romiplostim with eltrombopag and SoC. The model was driven by platelet response (platelet count ≥50 × 10(9)/L), which determined effectiveness and progression along the treatment pathway, need for rescue therapy (e.g. intravenous immunoglobulin [IVIg] and steroids) and risk of bleeding. Probability of response, mean treatment duration, average time to initial response and utilities were derived from clinical trials and other published evidence. Treatment sequences and healthcare utilization practice were validated by Irish clinical experts. Costs were assessed in for 2011 and included drug acquisition costs and costs associated with monitoring patients and management of bleeding, as available from published Irish reimbursement lists and other relevant sources. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Romiplostim treatment resulted in an average of 20.2 fewer administrations of rescue medication (IVIg or intravenous steroids) over a patient lifetime than eltrombopag, and 29.3 fewer rescue medication administrations than SoC. Romiplostim was dominant, with cost savings of 13,258 and 22,673 and gains of 0.76 and 1.17 quality-adjusted life-years (QALYs), compared with eltrombopag and SoC, respectively. Romiplostim remained cost effective throughout a variety of potential scenarios, including short-term TPOra treatment duration (1 year). One-way sensitivity analysis showed that the model was most sensitive to variation in the cost of IVIg and use of romiplostim and IVIg. Probabilistic sensitivity analysis showed that romiplostim was likely to be cost effective in over 90 % of cases compared with eltrombopag, and 96 % compared with SoC at a willingness-to-pay threshold of 30,000 per QALY. CONCLUSIONS: Use of romiplostim in the ITP treatment pathway, compared with eltrombopag or SoC, is likely to be cost effective in Ireland. Romiplostim improves clinical outcomes by increasing platelet counts, reducing bleeding events and the use of IVIg and steroids, resulting in both cost savings and additional QALYs when compared with current treatment practices.

[Economic evaluation of Thrombopoietin Receptor Agonists in the treatment of chronic primary immune thrombocytopenia]. / Evaluación económica del tratamiento de la trombocitopenia inmune primaria crónica refractaria con agonistas del receptor de la trombopoyetina.

PURPOSE: To develop a tool to assist the decision-making for selection of Thrombopoyetin Receptor Agonists of adult patients with chronic immune primary thrombocytopenia (PTI). METHODS: Stochastic cost-effectiveness analysis with a 6-Health- States Markov model: stable, bleeding type 2, 3 or 4, post-type 4 bleeding and death. Each simulation analyzes a randomly generated scenario that describes patients characteristics, results measured in quality adjusted life years (QALYs) and costs (in ?2011). Distributions were obtained from the Spanish data of the European health survey of 2009, the INE estimate of population for 2011 and the 6-months clinical studies for Eltrombopag and Romiplostim. Utility values were obtained from the literature and the costs from Spanish official rates lists. A set of 10.000 random scenarios were generated and the patients evolution of each scenario was simulated during a time horizon of five years (in 2-weeks cycles). National Health System Perspective was used and the annual discount rate was set at 3%. RESULTS: Eltrombopag showed more effectiveness in 9.983 scenarios and there was no difference in 17. In 7.048 scenarios the alternative Eltombopag was dominant. It was cost-effective in another 19 (threshold 30,000 ??/AVAC). CONCLUSIONS: Eltrombopag was the most cost-effective alternative in 70,67% of the simulated scenarios and its use could produce lower costs to the NHS.

Objetivo: Desarrollar una herramienta de apoyo a la decisión en la selección de agonistas del receptor de trombopoyetina en el tratamiento de pacientes adultos con trombocitopenia inmune primaria crónica (PTI) refractaria. Métodos: Análisis coste-efectividad estocástico con un modelo de Markov de seis estados: estable, sangrado tipo 2, 3 ó 4, post-sangrado 4 y muerte. Cada simulación analiza un escenario aleatoriamente generado que describe las características del paciente, los resultados medidos en años de vida ajustados a calidad (AVACs) y los costes (en ?2011). Se obtuvieron distribuciones a partir de los datos para España de la Encuesta Europea de Salud de 2009, de la estimación de población para 2011 del INE, de los estudios a 6 meses de Eltrombopag y Romiplostim, de las utilidades obtenidas de la bibliografía y de las tarifas oficiales en España para procesos y actividad. Se generaron 10.000 escenarios aleatorios y se simuló la evolución de los pacientes de cada escenario durante un horizonte temporal de cinco años (ciclos de dos semanas). Perspectiva del Sistema Nacional de Salud (SNS). Tasa de descuento anual del 3% para costes y efectos. Resultados: En 9.983 escenarios Eltrombopag mostró mayor efectividad y en 17 no hubo diferencias. Eltombopag fue la alternativa dominante en 7.048 escenarios y la más coste efectiva en otros 19 (umbral 30.000 ?/AVAC). Conclusiones: Eltrombopag es la alternativa más coste-efectiva en el 70,67% de los escenarios simulados, por lo que su uso podría producir menores costes al SNS.

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.

A pharmaco-economic evaluation of deferasirox for treating patients with iron overload caused by transfusion-dependent thalassemia in Taiwan.

BACKGROUND/PURPOSE: The newly available iron chelator deferasirox (Exjade, Novartis) is expected to provide better long-term clinical outcomes and improved quality of life for patients with thalassemia than its predecessor, deferoxamine (Desferal, Novartis), because of its oral tablet form. METHODS: We used the Markov model to estimate total additional lifetime costs and quality-adjusted life years (QALYs) gained with deferasirox versus deferoxamine in patients with transfusion-dependent thalassemia. Patients were assumed to be 2 years of age at initiation of chelation therapy. Clinical outcomes in terms of morbidity and mortality from associated complications and life expectancy for the study population were estimated using the databases of the Bureau of National Health Insurance and the Health and Vital Statistics of Taiwan. Treatment costs were based on analyses of health insurance claims for patients with transfusion-dependent thalassemia. Utilities in terms of quality of life were also included in the model. The incremental cost-utility ratio of deferasirox versus deferoxamine was defined by the ratio of the difference in expected lifetime costs to the difference in QALYs. One-way sensitivity analyses were performed to examine the robustness of the results to key assumptions. RESULTS: Patients treated with deferasirox are expected to experience a lower incidence of associated complications and obtain 2.3 QALYs (discounted) at an additional lifetime cost of US$36,291 per patient (US$15,596 per QALY). Sensitivity analyses showed that the unit drug cost of deferasirox had the greatest impact on the incremental cost-utility ratio. In addition, the incremental cost-utility ratio will increase by delaying the starting age (2 years of age in our study) of chelation therapy. CONCLUSION: Compared with infusional deferoxamine, oral deferasirox improved clinical outcomes and quality of life in terms of iron chelation in transfusion-dependent patients with thalassemia at a reasonable cost from a healthcare perspective.

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.

Improving drug adherence using fixed combinations caused beneficial treatment outcomes and decreased health-care costs in patients with hypertension.

We enrolled 196 patients with hypertension who were already being treated with free-drug combinations of angiotensin-II receptor blocker (ARB) and amlodipine. The free-drug combinations of ARB and amlodipine were replaced with the same dose of the fixed-dose combinations. The average home blood pressure (BP) in all patients receiving fixed-dose combinations was significantly lower than those receiving free-drug combinations (131 ± 10/75 ± 8 vs. 136 ± 11/77 ± 9 mm Hg, P < .01) accompanied with increasing drug adherence. After lowering BP by fixed-dose combinations, the costs for medications decreased by 31% over the 3 months.

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.

Eltrombopag for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of eltrombopag (GlaxoSmithKline) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with chronic immune or idiopathic thrombocytopenic purpura (ITP), as part of the their Single Technology Appraisal (STA) process. The Aberdeen Technology Assessment Review (TAR) Group, commissioned to act as the evidence review group (ERG), critically reviewed and supplemented the submitted evidence. This paper describes the company submission, the ERG review and NICE's subsequent decisions. The ERG critically appraised the clinical and cost-effectiveness evidence submitted by the manufacturer, independently searched for relevant literature, conducted a critical appraisal of the submitted economic models and explored the impact of altering some of the key model assumptions as well as combining relevant sensitivity analyses. Three trials were used to inform the safety and efficacy aspects of this submission; however, one high-quality randomized controlled trial (RAISE study) was the principal source of evidence and was used to inform the economic model. Eltrombopag had greater odds of achieving the primary outcome of a platelet count between 50 × 10^9/L and 400 × 10^9/L during the 6-month treatment period than placebo (odds ratio [OR] 8.2, 99% CI 3.6, 18.7). In the eltrombopag group, 50/83 (60%) of non-splenectomized patients and 18/49 (37%) of splenectomized patients achieved this outcome. The median duration of response was 10.9 weeks for eltrombopag (splenectomized 6 and non-splenectomized 13.4) compared with 0 for placebo. Eltrombopag patients required less rescue medication and had lower odds of bleeding events for both the splenectomized and the non-splenectomized patients. For a watch-and-rescue strategy of care, the comparator was placebo and the ERG found that substantial reductions in the cost of eltrombopag are needed before the incremental cost per QALY is less than £30,000. There was significant uncertainty, with the incremental cost-effectiveness ratio (ICER) reported varying from £33,561 to £103,500 per QALY (splenectomized) and £39,657 to £150,245 per QALY (non-splenectomized). All costs are presented in £, year 2008 values, as this was the costing year for the manufacturer's model. Other than bleeding, no adverse events were modelled. In relation to the long-term treatment model, the ERG questioned the robustness of the use of non-randomized non-comparative data. The base-case results restricting the time horizon to 2 years and prescribing eltrombopag as second-line treatment post-rituximab were found to be favourable towards eltrombopag. As rituximab is not a licensed treatment for ITP, the ERG were concerned that its inclusion may not be reflective of clinical practice. None of the treatment sequences resulted in an ICER approaching the recommended threshold of £30,000 per QALY gained. Eltrombopag appears to be a safe treatment for ITP (although long-term follow-up studies are awaited) and has short-term efficacy. However, NICE found based on the evidence submitted and reviewed that there was no robust evidence on the long-term efficacy or cost effectiveness of eltrombopag and a lack of direct evidence for eltrombopag tested against other relevant comparators.