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INTRODUCTION: The most notable challenge facing hemophilia A treatment is the development of inhibitors against factor VIII, resulting in increased clinical and socioeconomic burdens due to the need for expensive bypassing agents (BPAs). Although immune tolerance induction (ITI) is currently the primary approach for inhibiting and reducing the inhibitors, the lengthy duration of ITI necessitates the continued use of BPA to manage bleeding episodes. In this study, we aimed to obtain real-world evidence on the clinical and economic aspects and associated burdens experienced by patients with hemophilia A with inhibitors undergoing ITI in Korea. METHODS: Claims data from January 1, 2007, to December 31, 2020, were used in this study. The study cohort comprised patients with hemophilia A undergoing ITI, who were categorized into three groups: successful, failed, or continuation of ITI. We evaluated clinical and economic burdens, including monthly healthcare visits, medication costs, and total medical expenses. RESULTS: The study involved 33 cases of ITI across 32 patients. Excluding seven continuation cases where success could not be determined at the observation point, the estimated success rate of ITI was 80.8 %. The median duration of ITI for all patients was 25.7 months. While no significant disparities were noted in the ITI duration between successful and unsuccessful cases (24.51 vs. 25.66 months), substantial discrepancies were observed in the duration of BPA usage (11.10 vs. 25.66 months) and the number of prescribed BPAs (1.79 vs. 2.97). CONCLUSION: Successful ITI reduced both clinical and economic burdens, resulting in decreased monthly medication expenses and overall medical costs.
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Hemofilia A , Tolerancia Inmunológica , Humanos , Hemofilia A/economía , Hemofilia A/inmunología , Hemofilia A/tratamiento farmacológico , República de Corea , Masculino , Niño , Adulto , Adolescente , Preescolar , Factor VIII/uso terapéutico , Factor VIII/inmunología , Factor VIII/economía , Costo de Enfermedad , Adulto Joven , Femenino , Lactante , Costos de la Atención en SaludRESUMEN
INTRODUCTION: rVIII-SingleChain, a recombinant factor VIII (rFVIII), has demonstrated safety and efficacy in patients with hemophilia A in clinical trials and real-world evidence. This analysis aimed to estimate the potential budget impact of increasing the usage of rVIII-SingleChain for the prophylactic treatment of hemophilia A over 3 years in Italy. METHODS: Patients with moderate and severe hemophilia A receiving prophylaxis were included in the analysis. Epidemiological data were obtained from published literature. Mean product consumption and mean annual bleeding rate for rVIII-SingleChain, rFVIIIFc, octocog alfa and BAY 81-8973 were based on pooled real-world data from Italy, Germany and US. A budget impact model has been developed in order to compare two scenarios: a base-case scenario where current rVIII-SingleChain shares are kept constant over 3 years and an alternative scenario where rVIII-SingleChain shares increase by taking from other rFVIII products. Analysis 1 was based on the current Italian list prices and Analysis 2 considered current regional acquisition prices for both scenarios. RESULTS: Annually, adult patients treated with rVIII-SingleChain prophylaxis are expected to consume 324,589 units per patient, resulting in annual costs of 240,196 per patient. In Analysis 1, comparing the base case (constant market share of 9% rVIII-SingleChain over time) with the alternative scenario (higher rVIII-SingleChain market share and increasing from 15% in the first year to 25% in the third year), the total expenditure for prophylaxis using rFVIII products is expected to decrease by 1.4 million in Year 1, by 3.1 million in Year 2 and by 5.4 million in Year 3. In Analysis 2 based on regional prices, the results remained consistent. DISCUSSION/CONCLUSION: This analysis suggests that increasing utilization of rVIII-SingleChain in hemophilia A patients may lead to cost savings as a result of reduced consumption with uncompromised efficacy in bleed protection.
Why was the study done? Hemophilia A is a rare inherited bleeding disorder. People with severe hemophilia are more likely to bleed compared to people without hemophilia and bleeds can occur spontaneously or in response to trauma. Patients are treated with medication to reduce the chance of bleeding. However, the cost of treating patients with hemophilia can be high and place demands on the healthcare system.What did we do and find?This study looked at the cost of treating people with hemophilia in Italy and used a type of economic analysis (called budget impact modelling) to estimate the effect of increasing the use of a particular medication (rVIII-SingleChain), compared to other medications that are available. Different variations of the model were tested to compare a range of scenarios.The results of this analysis suggested that increasing the use of rVIII-SingleChain may lead to cost-savings for the Italian healthcare system, compared to using the other currently available treatments. This analysis suggests that the use of rVIII-SingleChain enables people with hemophilia A to remain protected from bleeds, whilst using less product compared to other available medications.What is the influence of this study on the wider field?This type of analysis can be useful to healthcare systems, to guide the decision-making process regarding which medications to use or when making decisions related to healthcare policy.
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Factor VIII , Hemofilia A , Adulto , Humanos , Presupuestos , Factor VIII/economía , Factor VIII/uso terapéutico , Alemania , Hemofilia A/tratamiento farmacológico , Hemorragia/inducido químicamente , Italia , Costos y Análisis de CostoRESUMEN
BACKGROUND AND OBJECTIVE: A cost-minimization model was developed to compare recombinant factor VIII Fc (rFVIIIFc) and emicizumab as prophylaxis for hemophilia A without inhibitors. METHODS: The model was based on 100 patients from the healthcare payer perspective in the UK, France, Italy, Spain, and Germany (5-year time horizon). Costs included: drug acquisition; emicizumab wastage by bodyweight (manufacturer's dosing recommendations); and additional FVIII for breakthrough bleeds. Scenario analyses (UK only): reduced emicizumab dosing frequency; and emicizumab maximum wastage. RESULTS: Total incremental 5-year savings for rFVIIIFc rather than emicizumab use range from 89,320,131 to 149,990,408 in adolescents/adults (≥12 years) and 173,417,486 to 253,240,465 in children (<12 years). Emicizumab wastage accounts for 6% of its total cost in adolescents/adults and 26% in children. Reducing the emicizumab dosing frequency reduces the incremental cost savings with rFVIIIFc, but these remain substantial (adolescents/adults, >92 million; children >32 million). Maximum emicizumab wastage increases by 86% and 106%, respectively, increasing the incremental cost savings with rFVIIIFc to 125,352,125 and 105,872,727, respectively. CONCLUSION: Based on cost-minimization modeling, rFVIIIFc use for hemophilia A prophylaxis in patients without inhibitors is associated with substantial cost savings in Europe, reflecting not only higher acquisition costs of emicizumab, but also other costs including wastage related to available vial sizes.
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Anticuerpos Biespecíficos , Anticuerpos Monoclonales Humanizados , Factor VIII , Hemofilia A , Adolescente , Adulto , Anticuerpos Biespecíficos/economía , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Monoclonales Humanizados/economía , Anticuerpos Monoclonales Humanizados/uso terapéutico , Niño , Costos y Análisis de Costo , Europa (Continente) , Factor VIII/economía , Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , HumanosRESUMEN
BACKGROUND: A shift from a standard to a personalized prophylaxis has been increasingly adopted in patients with severe haemophilia A (SHA). This approach has raised the likelihood of a significant variability in the prophylactic approaches and the relative Factor VIII (FVIII) consumptions. The aim of our study was to assess the treatment variability of SHA patients without inhibitors and on prophylaxis regimen in Italy. MATERIAL AND METHODS: Data reported in the National Registry of Congenital Coagulopathies (NRCC) were analysed to assess treatment distribution within SHA patients without inhibitors, focussing on FVIII consumption in 2017, associated with prophylaxis regimen. The analysis was stratified based on age groups and Italian regions to describe the variability of FVIII consumption in Italy. RESULTS: In 2017, the Registry reported the therapeutic plans of 1068 SHA patients without inhibitors on prophylaxis. The mean (95% CI) individual consumption ranges from 123 127 IU (99 736-146 518) in the age group 0-6 years to 345 000 IU (336 000-354 000) in the age group >20 years. A significant FVIII consumption variability was identified within the adult population. Regions with less than 50 patients reported the higher variability in mean FVIII consumption per patient-year within the different age groups. Similar difference in FVIII consumption variability was reported also in the age groups comparing "low," "middle" and "high" patient volume regions. DISCUSSION: A reliable estimation of FVIII consumption for patients' treatment is necessary to manage and plan the appropriate budget and keep treatment's costs affordable. However, without the implementation of a methodology aiming to assess the overall value produced by these FVIII consumptions, the scenario will keep driven by FVIII consumptions, its costs and the budget available. An effort by haemophilic community, haemophilia treatment centres and institutions is required to develop and share this cultural shift in improving haemophilia management and assessment.
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Quimioprevención/métodos , Costos de los Medicamentos/estadística & datos numéricos , Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Medicina de Precisión/métodos , Sistema de Registros , Adolescente , Adulto , Factores de Edad , Quimioprevención/economía , Niño , Preescolar , Esquema de Medicación , Factor VIII/economía , Femenino , Hemofilia A/sangre , Hemofilia A/economía , Hemofilia A/patología , Humanos , Lactante , Recién Nacido , Italia , Masculino , Medicina de Precisión/economía , Índice de Severidad de la EnfermedadRESUMEN
At an upfront price of $2.125 million, the one-time gene therapy onasemnogene abeparvovec for spinal muscular atrophy, a rare neuromuscular disorder that is usually fatal by 2 years of age if untreated, has been called the "most expensive drug ever." This flawed characterization raises important methodological and policy issues regarding valuation of high-cost treatments. We reviewed several other high-cost therapies-with a particular focus on hemophilia A treatment-studied by the nonprofit Institute for Clinical and Economic Review (ICER). In ICER's summary report of 2 treatments for managing hemophilia A, published in this month's JMCP issue, the estimated $15-$18 million lifetime cost of factor VIII is characterized as "far too high," representing "a failure of competition [that] builds a platform for pricing of treatments that will only exacerbate these problems." Current literature indicates several factors underlying high factor VIII treatment cost (eg, historical pattern of innovation and lack of market competition) that may also drive the pricing dynamics of advanced therapies for other rare diseases. When a treatment's price is driven high (or "distorted"), an economic principle known as "theory of the second best" suggests that market price becomes a poor estimate of social opportunity cost, and adjustments should be made for such distortions. In any case, a high-cost standard of care creates an opportunity for new technology to generate cost savings, providing an inducement for market entry. Recognizing that this potentially creates a tendency to produce price distortions for new treatments, ICER has attempted to apply some ad hoc adjustments. However, challenges remain in creating a "level playing field" across different disease-modifying or potentially curative innovations (eg, one-time therapy vs ongoing or lifelong treatment with repeated doses). While additional policy work is needed to address this dilemma, it would clearly be misleading to assume that gene therapies are inherently expensive. Rigorous economic evaluation of novel therapies requires careful comparison of lifetime cost and benefits vs standard of care, including adjustments for pricing distortions. Fortunately, economic theory suggests that we could adjust to this circumstance by using the social opportunity costs of interventions based on an appropriate variable cost-effectiveness threshold that would be higher for rare severe diseases. DISCLOSURES: The research reported in this Viewpoints article was funded by Novartis Gene Therapies, Inc. Garrison and Jiao were paid by Novartis Gene Therapies, Inc., to conduct this research. Garrison has also received consulting fees from BioMarin, Inc, and UniQure. Dabbous is a full-time employee of Novartis Gene Therapies, Inc., and holds Novartis stock and stock options.
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Análisis Costo-Beneficio , Terapia Genética/economía , Terapia Genética/métodos , Costos de los Medicamentos/estadística & datos numéricos , Factor VIII/administración & dosificación , Factor VIII/economía , HumanosRESUMEN
BACKGROUND: Hemophilia A (HA) can result in bleeding events because of low or absent clotting factor VIII (FVIII). Prophylactic treatment for severe HA includes replacement FVIII infusions and emicizumab, a bispecific factor IXa- and factor X-directed antibody. OBJECTIVE: To develop an economic model to predict the short- and long-term clinical and economic outcomes of prophylaxis with emicizumab versus short-acting recombinant FVIII among persons with HA in the United States. METHODS: A Markov model was developed to compare clinical outcomes and costs of emicizumab versus FVIII prophylaxis among persons with severe HA from U.S. payer and societal perspectives. Patients started prophylaxis at age 1 year in the base case. Mutually exclusive health states considered were "no arthropathy," "arthropathy," "surgery," and "death." Serious adverse events, breakthrough bleeds, and inhibitor development were simulated throughout the modeled time horizon. In addition to the prophylaxis drug costs, patients could incur other direct costs related to breakthrough bleeds treatment, serious adverse events, development of inhibitors, arthropathy, and orthopedic surgery. Indirect costs associated with productivity loss (i.e., missed work or disabilities) were applied for adults. Model inputs were obtained from the HAVEN 3 trial, published literature, and expert opinion. The model used a lifetime horizon, and results for 1 year and 5 years were also reported. Deterministic sensitivity analyses and scenario analyses were conducted to assess robustness of the model. RESULTS: Over a lifetime horizon, the cumulative number of all treated bleeds and joint bleeds avoided on emicizumab versus FVIII prophylaxis were 278.2 and 151.7, respectively. Correspondingly, arthropathy (mean age at onset: 12.9 vs. 5.4 years) and FVIII inhibitor development (mean age at development: 13.9 vs. 1.1 years) were delayed. Total direct and indirect costs were lower for emicizumab versus FVIII prophylaxis for all modeled time horizons ($97,159 vs. $331,610 at 1 year; $603,146 vs. $1,459,496 at 5 years; and $15,238,072 vs. $22,820,281 over a lifetime horizon). The sensitivity analyses indicated that clinical outcomes were sensitive to efficacy inputs, while economic outcomes were driven by the discount rate, dosing schedules, and treatments after inhibitor development. Results for moderate to severe patients were consistent with findings in the severe HA population. CONCLUSIONS: The model suggests that emicizumab prophylaxis confers additional clinical benefits, resulting in a lower number of bleeding events and delayed onset of arthropathy and inhibitor development across all time assessment horizons. Compared with short-acting recombinant FVIII, emicizumab prophylaxis leads to superior patient outcomes and cost savings from U.S. payer and societal perspectives. DISCLOSURES: Funding for this study was provided by Genentech. Raimundo and Patel are employees of Genentech and own stock or stock options. Zhou, Han, Ji, Fang, Zhong, and Betts are employees of Analysis Group, which received consultancy fees from Genentech for conducting this study. Mahajerin received consultancy fees from Genentech for work on this study. Portions of this research were presented as a poster at the 2018 American Society of Hematology Conference; December 1-4, 2018; San Diego, CA.
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Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Factor VIII/administración & dosificación , Hemofilia A/tratamiento farmacológico , Modelos Económicos , Adolescente , Anticuerpos Biespecíficos/economía , Anticuerpos Monoclonales Humanizados/economía , Niño , Preescolar , Coagulantes/administración & dosificación , Coagulantes/economía , Factor VIII/economía , Hemofilia A/economía , Humanos , Lactante , Artropatías/epidemiología , Masculino , Cadenas de Markov , Factores de Tiempo , Estados UnidosRESUMEN
BACKGROUND: Hemophilia is known as one of the most common coagulation disorders whose treatment costs are particularly high in developing countries, and about 90% of them are related to factor VIII (FVIII) and direct medical costs (DMCs). Thus, the present study aimed to analyze cost-utility of two FVIII diet therapies prepared using blood plasma and recombinant technique. METHODS: This study was an economic evaluation fulfilled through a cost-utility approach. To this end, a total number of 120 patients were randomly selected using Krejcie & Morgan's Table and then received blood plasma and recombinant FVIII. The decision tree structure was also utilized to estimate economic and clinical outcomes. Moreover, costs were reviewed from societal perspective. Quality-adjusted life year (QALY) was subsequently determined as the measure of effectiveness (MOE). Besides, one-way (univariate) sensitivity analysis was performed to quantify uncertainty effects of the study parameters. The information was ultimately analyzed using the TreeAge Pro 2011 and the Microsoft Office Excel 2010 software. RESULTS: The results revealed that the recombinant diet therapy had higher costs and effectiveness compared with blood-plasma-derived FVIII, so that the mean costs of these two diet therapies were equal to 37,624 and 20,349 purchasing power parity (PPP) $ with utility scores of 0.78 and 0.62; respectively. Since the incremental cost-effectiveness ratio (ICER) for the recombinant medications was over three times of the threshold level, it was considered as overwhelming because of its high cost in spite of its better effectiveness. Moreover, the results of one-way (univariate) sensitivity analysis demonstrated the highest sensitivity to the utility in patients who had been injected with blood-plasma-derived FVIII and had been successfully treated. CONCLUSION: The study results revealed that FVIII prepared using blood plasma for hemophilia A patients had higher cost-effectiveness compared with that made using recombinant technique. Graphical abstract.
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Factor VIII/economía , Factor VIII/uso terapéutico , Hemofilia A/dietoterapia , Hemofilia A/economía , Plasma , Análisis Costo-Beneficio , Factor VIII/genética , Humanos , Años de Vida Ajustados por Calidad de Vida , Proteínas Recombinantes/economía , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Recombinant factor VIII (rFVIII) products have been developed with improved pharmacokinetics, offering some patients the potential to extend dosing intervals, thereby reducing their dosing frequency while minimizing the occurrence of bleeding events. No clinical trials have been conducted to compare the bleeding rates and use of these long-acting products. OBJECTIVES: To (a) assess real-world use of prophylaxis regimens in patients using 1 of 3 different long-acting products-rVIII-SingleChain, rFVIIIFc, or PEG-rFVIII; and (b) compare bleeding rates, dosing frequency, and factor consumption in 3 cohorts of patients. For rVIII-SingleChain patients, these measures were also compared with the prior products these patients used. METHODS: De-identified patient chart data were collected from 11 hemophilia treatment centers in the United States. Patients were included if they had been treated with rVIII-SingleChain, rFVIIIFc, or PEG-rFVIII prophylaxis for ≥ 8 weeks at the time of data collection. Matching for age and disease severity was attempted between the 3 patient groups. Data were also collected for patients who switched from their prior FVIII product to prophylaxis with rVIII-SingleChain. RESULTS: Data were obtained for 120 male patients. The majority of patients were dosing 2 times per week or less frequently (rVIII-SingleChain 65.0%, rFVIIIFc 70.0%, and PEG-rFVIII 72.5%). Annualized bleeding rates were comparable among the 3 cohorts, with median (mean) values of 2.0 (2.6) with rVIII-SingleChain and rFVIIIFc, and 3.0 (3.7) with PEG-rFVIII. The overall median (mean) FVIII consumption in IU per kg per week (IU/kg/week) was 91.9 (91.1) with rVIII-SingleChain, 108.5 (103.6) with rFVIIIFc, and 97.6 (111.0) with PEG-rFVIII, resulting in expected mean annual consumption of 322,140 IU, 361,816 IU, and 373,100 IU, respectively, for a 70 kg patient aged ≥12 years. The mean consumption was significantly different among the 3 products for all patients (P = 0.0164) and for those dosed 2 times per week (P < 0.0001). Among patients infusing 2 times per week, median (mean) consumption with rVIII-SingleChain was 83.8 (81.2) IU/kg/week, compared with 109.6 (104.4) IU/kg/week for rFVIIIFc and 92.1 (91.5) IU/kg/week for PEG-rFVIII. Additionally, switching from prophylaxis with prior FVIII products to rVIII-SingleChain increased the proportion of patients dosing ≤ 2 times per week (20% to 65%), decreased mean consumption (103.3 to 91.9 IU/kg/week; P = 0.0164), and maintained the mean annualized bleeding rates (2.9 to 2.6; P = 0.5665). CONCLUSIONS: Results for rVIII-SingleChain confirm the findings from its pivotal trial. Analyses of annualized bleeding rates demonstrate comparable clinical outcomes of rVIII-SingleChain to the other 2 long-acting products assessed. In patients aged ≥ 12 years, rVIII-SingleChain prophylaxis may result in an 11.0% and 13.7% lower mean factor consumption than rFVIIIFc and PEG-rFVIII, respectively, representing a potential cost-saving opportunity of 34% in both cases-at the current wholesale acquisition cost of the corresponding products. In addition, in patients using rVIII-SingleChain prophylactically, consumption was reduced compared with their prior products, while bleeding control was well maintained. DISCLOSURES: This study was funded by CSL Behring. Analyses were conducted by Adivo Associates. Maro is an employee of Adivo Associates. Desai and Yan are employees of CSL Behring. Simpson has received consulting honoraria for participation in advisory boards for CSL Behring, Genentech, Octapharma, and Bioverativ and speakers bureau for Bayer and Novo Nordisk. Data were presented in part at the Hemostasis and Thrombosis Research Society; May 9-11, 2019; New Orleans, LA, and at the International Society on Thrombosis and Haemostasis; July 6-10, 2019; Melbourne, Australia.
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Factor VIII/administración & dosificación , Hemofilia A/tratamiento farmacológico , Hemorragia/prevención & control , Adolescente , Niño , Ahorro de Costo , Esquema de Medicación , Costos de los Medicamentos , Factor VIII/economía , Factor VIII/farmacocinética , Semivida , Hemofilia A/complicaciones , Hemofilia A/economía , Hemorragia/epidemiología , Hemorragia/etiología , Humanos , Masculino , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/economía , Proteínas Recombinantes/farmacocinética , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
Introduction: Hemophilia is a very expensive disease. Ameliorations in the management of hemophilia cause increased patient survival, more complex disease management, and augmented treatment costs. A literature search related to the cost of hemophilia was analyzed.Areas covered: Clotting factor concentrates, which are the keystone of management, are costly. In fact, the yearly expenditure in the USA is 250,000 USD per adult patient. Indirect expenses also play a part in the economic load, and include lost productive capacity, uncompensated caretaker tariffs, and hemophilia-related physical handicap. Factor concentrates are responsible for more than 90% of the direct health-care expenditures of hemophilia. In an evaluation of the cost of management with high-dose prophylaxis in previously untreated patients from childbirth to puberty, including immune tolerance induction (ITI), the average annual treatment cost (Euros per kilogram) was 4391 EUR (approximately 4865 USD), and the average ITI cost was 383,448 EUR (approximately 424,860 USD). The expected ITI recovery period in the aforementioned evaluation was 1.8 years. To reduce costs, strategies such as disease management programs and drug pricing programs have also been implemented.Expert opinion: Knowing the current cost of hemophilia is essential to ensure that patients are treated as efficiently as possible.
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Factor VIII/economía , Costos de la Atención en Salud , Hemofilia A/economía , Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Humanos , Estados UnidosRESUMEN
BACKGROUND: The recombinant factor VIII (rFVIII)-IgG1 Fc fusion protein (rFVIII-Fc) was the first available extended half-life rFVIII, shown to prolong dosing intervals of individualised prophylaxis in patients with severe haemophilia A, maintaining low bleeding rates and unchanged or lower FVIII dose versus standard half-life (SHL) rFVIII. Few data are available about real-world experience with rFVIII-Fc, including criteria for patient switching from SHL products, follow up and prophylaxis optimisation. MATERIALS AND METHODS: A single-centre retrospective study was designed to review patients switched to rFVIII-Fc, based on individual needs, after pharmacokinetic (PK) assessment, according to routine clinical practice. In patients with adequate post-switch follow up, data about rFVIII-Fc prophylaxis were compared with those from the last 18-months SHL rFVIII prophylaxis. RESULTS: Of 25 candidates, 18 patients (15 severe, 3 moderate; aged 9-62 years; 3 with inhibitor history) started rFVIII-Fc regimens, with comparable FVIII weekly dose and reduced infusion frequency (mean -30%) in all 17 patients previously on SHL rFVIII prophylaxis thrice weekly or every other day. Over a mean 18-month follow up in 13 patients, compared with SHL products, further reduced infusion frequency (mean -40%; p<0.001; interval ≥4 days in 9 patients), improved treatment satisfaction (Hemo-sat questionnaires), significantly lower FVIII weekly dose and annual consumption (mean -12%; p=0.019), comparable bleeding rates and FVIII trough levels, and improved management of breakthrough bleeding were observed. von Willebrand Factor Antigen (VWF:Ag) correlated to PK variables and both had relationships with rFVIII-Fc weekly dose, increasing statistical significance over the follow-up period. No inhibitors or drug-related adverse events were recorded. DISCUSSION: In this real-world series of patients, a switch to rFVIII-Fc, based on careful assessment of clinical needs, PK testing and treatment monitoring, was able to optimise individual convenience, efficacy and costs of prophylaxis.
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Factor VIII , Hemofilia A , Hemorragia , Fragmentos Fc de Inmunoglobulinas , Proteínas Recombinantes de Fusión , Adolescente , Adulto , Niño , Costos y Análisis de Costo , Factor VIII/administración & dosificación , Factor VIII/economía , Factor VIII/farmacocinética , Estudios de Seguimiento , Hemofilia A/sangre , Hemofilia A/tratamiento farmacológico , Hemofilia A/economía , Hemorragia/sangre , Hemorragia/economía , Hemorragia/prevención & control , Humanos , Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Fragmentos Fc de Inmunoglobulinas/economía , Masculino , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/economía , Proteínas Recombinantes de Fusión/farmacocinética , Estudios RetrospectivosRESUMEN
AIM: To assess effect of low dose prophylaxis in hemophilics in terms of bleeding, joint function, QoL and cost-effectiveness. METHODS: Analytic study done during one year among 70 adult hemophilics. In observation period (12 weeks), on-demand factor and during prophylaxis (12 weeks), low dose factor was given (Factor VIII 10 IU/KgBW biweekly for haemophilia A and Factor IX 20 IU/KgBW weekly for haemophilia B). Clinical joint assessment was done by Gilbert score and improvement by WFH definitions. RESULTS: Bleed reduced by 68.99% in moderate hemophilics (40 v/s 129) and 64.86% in severe hemophilics (26 v/s74) (p<0.05). During observation in moderate hemophilics, joint, soft tissue and mucosal bleeds occurred in frequency of 120, 1 and 8. This was reduced to 39 joint bleeds, 1 soft tissue bleed and no mucosal bleed during prophylaxis. In severe hemophilics, 70 joint, 2 soft tissue bleeds and 2 mucosal bleeds occurred during observation which reduced to 26 joint bleeds without soft tissue/mucosal bleed in prophylaxis. Bleeding episodes decreased by 65.79% in joints, 66.67% in soft tissues, 100% mucosal bleeds. After prophylaxis one joints (0.61 %) showed good improvement in joint function, thirty (18.18 %) joints showed moderate improvement and ninety two joints (55.76 %) showed mild improvement in joint function. Hospitalization reduced by 60.34% (163 v/s 411) and absenteeism by 53.73% (279 v/s 603). Factors consumption reduced by 12.33 % during prophylaxis period. CONCLUSION: The low dose prophylaxis strategy significantly decreased the subsequent episodes of total bleeds including joint bleeds and improved the joint function as well as quality of life.
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Coagulantes , Hemartrosis , Hemofilia A , Adulto , Coagulantes/economía , Coagulantes/uso terapéutico , Análisis Costo-Beneficio , Factor IX/economía , Factor IX/uso terapéutico , Factor VIII/economía , Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hemofilia A/etiología , Hemofilia A/prevención & control , Humanos , Calidad de Vida , Resultado del TratamientoRESUMEN
BACKGROUND: Extended half-life (EHL) factor VIII (FVIII) and IX (FIX) products are intended to decrease the burden of prophylaxis for patients with haemophilia A or B. Whether these newer concentrates have led to meaningful clinical practice change remains vague. AIM: To characterize the longitudinal use of standard (SHL) and EHL factor concentrates at haemophilia treatment centres (HTCs), using the ATHNdataset, a US database of 138 ATHN-affiliated HTCs. METHODS: Factor concentrate use among moderate and severe haemophilia A and B patients without inhibitors was analysed at three time points over 18 months. RESULTS: Use of EHL concentrates rose from 10% of patients to 22% during this study. EHL FVIII prophylaxis is prescribed to the minority of patients, 28%; EHL FIX now predominates for prophylaxis, 52%. Rates of prescribed EHL products varied significantly by age group and HTC region. Median prescribed prophylaxis for SHL compared to EHL products was FVIII 6240 and 5200 and FIX 6968 and FIX 3900 IU/kg/y, respectively. On-demand EHL use has grown but has minimal contribution to overall usage (2%). CONCLUSION: Haemophilia treatment centre region and patient age impact the rate of adoption of EHL products; however, EHL prescribing continues to rise nationally, particularly for EHL FIX. Careful attention to annual cost of prophylaxis is imperative as the decrease in median EHL prophylaxis consumption is not offset by the higher unit cost of these products. It is unclear how further growth in use of EHLs will be impacted by emerging non-factor replacement and gene therapies.
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Costos y Análisis de Costo , Factor IX/economía , Factor IX/uso terapéutico , Factor VIII/economía , Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hemofilia B/tratamiento farmacológico , Adolescente , Adulto , Factores de Edad , Niño , Prescripciones de Medicamentos/economía , Prescripciones de Medicamentos/estadística & datos numéricos , Factor IX/farmacocinética , Factor VIII/farmacocinética , Femenino , Geografía , Semivida , Hemofilia A/metabolismo , Hemofilia B/metabolismo , Humanos , Estudios Longitudinales , Masculino , Estados Unidos , Adulto JovenRESUMEN
Objective: To assess real-world costs for patients with hemophilia A treated with bypassing agents versus factor VIII (FVIII) replacement. Methods: Claims data from a large US health insurer during 1 January 2006-30 September 2014 were used for analysis. Treated patients with hemophilia A were identified based on ≥1 medical claim with a diagnosis code for hemophilia A (ICD-9-CM 286.0) and ≥1 medical or pharmacy claim for bypassing therapy and/or FVIII replacement during 1 January 2007-31 August 2014. The bypassing therapy cohort comprised patients with ≥1 claim for bypassing therapy; all others were assigned to the factor replacement therapy cohort. Post-index hemophilia-related costs were computed as combined health plan plus patient paid amounts for medical claims with hemophilia A diagnosis code or hemophilia therapy procedure code (bypassing therapy, FVIII replacement therapy, desmopressin, antifibrinolytic therapy), as well as pharmacy claims for hemophilia therapy. Results: The study sample represented 580 patients: 50 (8.6%) in the bypassing therapy cohort (mean age: 38.5 years; mean post-index period: 2.1 years) and 530 (91.4%) in the factor replacement therapy cohort (mean age: 29.3 years; mean post-index period: 2.7 years). Compared with the factor replacement therapy cohort, mean per-patient-per-month hemophilia-related total costs were 4.8-fold higher in the bypassing therapy cohort ($57,232 vs. $11,899), comprising 4.4-fold higher medical costs ($45,911 vs. $10,352) and 7.3-fold higher outpatient pharmacy costs ($11,321 vs. $1547). Conclusions: Patients with hemophilia A treated with bypassing agents between 2007 and 2014 incurred substantially higher monthly hemophilia-related medical and pharmacy costs than patients treated only with FVIII replacement.
Asunto(s)
Costos de la Atención en Salud/estadística & datos numéricos , Fármacos Hematológicos , Hemofilia A , Adulto , Factor VIII/economía , Factor VIII/uso terapéutico , Fármacos Hematológicos/economía , Fármacos Hematológicos/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hemofilia A/economía , Hemofilia A/epidemiología , HumanosRESUMEN
Introduction: rFVIIIFC was the first extended half-life product to complete the phase 3 development program and be registered. It was developed to reduce the high treatment burden imposed by prophylaxis. It is now one of four extended half-life products available for a variety of indications in hemophilia A. This article focus on the efficacy use of rFVIIIFC in the prevention of bleeds in hemophilia A. Areas covered: This article provides an update on efficacy data from three clinical studies describing the use of rFVIIIFC in the treatment and prevention of bleeds in hemophilia A. The update includes the efficacy use of rFVIII in all age groups, in the perisurgical setting, in immune tolerance induction, and in improving the quality of life of patients. The role of rFVIIIFC prophylaxis in the face of rapidly evolving non-replacement therapy and gene therapy is summarized. Expert commentary: The role of rFVIIIFC in hemophilia A prophylaxis is uncertain in the light of development of newer prophylaxis agents with better route of administration, improved pharmacokinetic and superior efficacy profiles. While rFVIIIFC was primarily developed for prophylaxis in hemophilia A, this role may change in the face of competitive extended half-life products and non-replacement therapies.
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Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Animales , Factor VIII/administración & dosificación , Factor VIII/economía , Factor VIII/farmacología , Hemofilia A/prevención & control , Hemostasis/efectos de los fármacos , Humanos , Tolerancia Inmunológica/efectos de los fármacos , Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Fragmentos Fc de Inmunoglobulinas/economía , Fragmentos Fc de Inmunoglobulinas/farmacología , Calidad de Vida , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/economía , Proteínas Recombinantes de Fusión/farmacología , Resultado del TratamientoRESUMEN
PURPOSE: To identify international units (IUs) dispensed and consequent expenditures for standard half-life (SHL) versus extended half-life (EHL) recombinant factor VIII (rFVIII) replacement products in hemophilia A patients in a real-world setting. DESIGN: Two U.S. claims databases were analyzed. METHODOLOGY: Number of IUs dispensed and quarterly expenditures for rFVIII products were collected from the Optum Clinformatics Data Mart and Truven Health MarketScan Databases. Truven claims were also analyzed for factor IUs dispensed and expenditures for patients with data for ≥3 months before and after switching to an EHL product. RESULTS: The Optum and Truven databases, respectively, included 276 (SHL, n=243; EHL, n=33) and 500 (SHL, n=409; EHL, n=91) hemophilia A patients. Median quarterly factor IUs dispensed in Optum were 10% higher with EHL versus SHL products over nine quarters, and 45% higher with EHL versus SHL products in Truven over 10 quarters. Median quarterly expenditures in the EHL cohort were 51% (individual quarterly medians range, 1%-101%) higher than in the SHL cohort in Optum and 122% higher (individual quarterly medians range, 1%-189%) in Truven. Twenty-nine Truven patients switched to an EHL product; median factor IUs dispensed varied quarterly. The lowest SHL and highest EHL values occurred in the quarter immediately before switching and the first quarter post-switch, respectively. Overall median quarterly expenditures were higher post-switch; this was consistent over seven quarters. CONCLUSION: We found higher expenditures over two years for hemophilia A patients using EHL versus SHL products. Switching to an EHL rFVIII product was associated with variable factor IUs dispensed and consistently higher expenditures.
Asunto(s)
Factor VIII/administración & dosificación , Factor VIII/economía , Gastos en Salud , Hemofilia A/tratamiento farmacológico , Costos y Análisis de Costo , Estudios Transversales , Bases de Datos Factuales , Sustitución de Medicamentos/economía , Semivida , Humanos , Revisión de Utilización de Seguros , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: Congenital haemophilia A (HA) is a rare, inherited, life-long bleeding disorder characterised by prolonged or spontaneous bleeding due to the lack of clotting factor VIII (FVIII) in the body. Treatment for HA involves FVIII replacement therapy and poses great economic burden to National Health Systems and to society. Availability of novel products as extended half-life clotting factor products might change treatment approches and their economic evaluation is essential for an informed treatment choice. Accordingly the objective of the present work is to analyse the economic impact of using efmoroctocog alfa (recombinant factor VIII-Fc fusion protein, rFVIIIFc) for the treatment of children and adults with severe congenital haemophilia A (HA). METHODS: A budget impact analysis was performed to estimate the economic impact of the introduction of rFVIIIFc in the market-mix of products for the treatment of HA. The analysis condidered a 3-year time horizon and the Italian National Health System (INHS) perspective. The model estimated drug costs associated with the treatment of HA in the current scenario - representing the marketplace forecast for the time period of interest assuming that rFVIIFc is not introduced - and a new scenario, assuming that rFVIIIFc is available in the market. The size of the target population was calculated using epidemiological national data. Univariate one-way sensitivity analyses and scenario analyses were performed. RESULTS: Overall 3-year costs of treating the HA population in the current scenario were 555,277,691 Euro for the INHS. With the introduction of rFVIIIFc, the costs were reduced to 541,897,466 Euro suggesting potential savings to the INHS of 13,380,255 Euro. Results were consistent at variation of most of the model's parameters; only in case of lower dosage of conventional products and higher dosage of rFVIIIFc, costs for the INHS increased, in both cases, of about 20 million Euro. CONCLUSIONS: The use of rFVIIIFc for the treatment of HA has been recently approved by the Italian Medicines Agency (AIFA) and this is the first study estimating the financial impact of this new therapeutic alternative in the Italian context. The analysis suggests that rFVIIIFc use does not result in higher expenditure for the INHS.
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Coagulantes/uso terapéutico , Factor VIII/uso terapéutico , Hemofilia A/terapia , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Adulto , Presupuestos , Niño , Coagulantes/economía , Análisis Costo-Beneficio , Factor VIII/economía , Semivida , Hemofilia A/economía , Hemorragia/tratamiento farmacológico , Hemorragia/economía , Humanos , Fragmentos Fc de Inmunoglobulinas/economía , Italia , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteínas Recombinantes de Fusión/economíaRESUMEN
BACKGROUND: Inhibitor development to factor VIII (FVIII) hemophilia therapy results in increased complications and substantial economic costs. The SIPPET study, the first randomized controlled trial to compare the immunogenicity of plasma-derived FVIII (pdFVIII)/von Willebrand factor (VWF) and recombinant-DNA-derived FVIII (rFVIII), demonstrated higher inhibitor rates in previously untreated patients (PUPs) treated with rFVIII than in PUPs treated with pdFVIII/VWF. OBJECTIVE: To quantify the economic impact of treating PUPs with pdFVIII/VWF vs rFVIII. METHODS: An Excel-based clinical and economic model was developed from a US healthcare payer perspective and run over a 5-year period. The analysis utilized a cohort approach to model patient treatment and outcomes over a monthly cycle to quantify differences in costs of FVIII, bypassing agents, and hospitalizations for serious bleeds. Rates of high-titer inhibitor development were obtained from the SIPPET study. Patients developing high-titer inhibitors were treated with immune tolerance induction (ITI). Patients who developed low-titer inhibitors and those who did not develop inhibitors continued their usual FVIII treatment. Patients who were successfully treated with ITI returned to FVIII treatment, while unsuccessfully treated patients received bypassing agents. Total costs per treated patient were estimated and a one-way sensitivity analysis was conducted to quantify the impact of parameter uncertainty on the model outcomes. RESULTS: Total cumulative costs per patient over 5 years were $834,621 for pdFVIII/VWF patients and $1,237,163 for rFVIII patients, representing a total saving of $402,542 per patient over the 5-year period, for an average annual saving of $80,508 per patient. CONCLUSIONS: Based on data from the SIPPET study, this analysis found that initiating FVIII treatment in severe hemophilia A PUPs with pdFVIII/VWF has the potential to offer substantial cost savings to healthcare payers, amounting to a one-third reduction in costs.
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Factor VIII/economía , Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Factor de von Willebrand/economía , Factor de von Willebrand/uso terapéutico , Costos y Análisis de Costo , Combinación de Medicamentos , Factor VIII/efectos adversos , Servicios de Salud/economía , Servicios de Salud/estadística & datos numéricos , Hemorragia/inducido químicamente , Hemorragia/economía , Humanos , Lactante , Masculino , Modelos Econométricos , Admisión del Paciente/economía , Admisión del Paciente/estadística & datos numéricos , Estados Unidos , Factor de von Willebrand/efectos adversosRESUMEN
AIM: For previously untreated patients (PUPs) with severe haemophilia A in Finland for the past 2 decades, the standard practice has been to start early primary prophylaxis. We evaluated the long-term clinical outcomes and costs of treatment with high-dose prophylaxis in PUPs from birth to adolescence, including immune tolerance induction (ITI). METHODS: From the medical records of all PUPs born between June 1994 and May 2013 in Finland, we retrospectively extracted data on clinical outcomes and healthcare use. Using linear mixed models, we analysed longitudinal clinical outcome data. To analyse skewed cost data, including zero costs, we applied hurdle regression. RESULTS: All 62 patients received early regular prophylaxis; totally, they have had treatment for nearly 700 patient-years. The median age of starting home treatment was 1.1 years. The mean (SD) annual treatment costs ( per kg) were 4391 (3852). For ages 1-3, ITI comprised over half of the costs; in other groups, prophylactic FVIII treatment dominated. With these high costs, however, clinical outcomes were desirable; median (IQR) ABR was low at 0.19 (0.07-0.46) and so was AJBR at 0.06 (0-0.24). Thirteen (21%) patients developed a clinically significant inhibitor, 10 (16%) with a high titre. All ITIs were successful. The mean costs for ITI were 383 448 (259 085). The expected ITI payback period was 1.81 (95% CI 0.62-12.12) years. CONCLUSIONS: Early high-dose prophylaxis leads to excellent long-term clinical outcomes, and early childhood ITI therapy seems to turn cost-neutral generally already in 2 years.
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Hemofilia A/tratamiento farmacológico , Hemofilia A/economía , Adolescente , Niño , Preescolar , Documentación , Factor VIII/economía , Factor VIII/inmunología , Factor VIII/uso terapéutico , Femenino , Finlandia , Costos de la Atención en Salud/estadística & datos numéricos , Hemofilia A/inmunología , Humanos , Tolerancia Inmunológica , Lactante , Recién Nacido , Masculino , Resultado del TratamientoAsunto(s)
Inhibidores de Factor de Coagulación Sanguínea/sangre , Factor VIII/administración & dosificación , Factor VIII/economía , Hemofilia A , Modelos Biológicos , Modelos Económicos , Costos y Análisis de Costo , Factor VIII/efectos adversos , Femenino , Hemofilia A/sangre , Hemofilia A/tratamiento farmacológico , Hemofilia A/economía , Humanos , MasculinoRESUMEN
OBJECTIVE: To explore the influence of medical insurance policy and charity assistance projects on the uptake and discontinuation of regular prophylaxis treatment in Chinese severe haemophilia A children. METHODOLOGY: This retrospective study was conducted on children with severe haemophilia A, who received FVIII prophylaxis treatment at 12 haemophilia centres in China from 1 November 2007 to 31 May 2013. RESULTS: The average duration of prophylaxis treatment received by haemophilia children significantly increased from 16.7 weeks in 2008 to 32.8 weeks in 2012 (P < .001). The main reason for prophylaxis acceptance included dissatisfaction with previous "on-demand" regimens, availability of improved local medical insurance policies and patient/family awareness of haemophilia. The main reason for subsequent discontinuation of prophylaxis was economic instability. The upper limit of insurance was up to RMB 150 000/y (~USD: 22 000/y) for 80.1% of the insured patients and would be sufficient to cover the continuous low-dose prophylaxis regimen. However, for many patients the burden of out-of-pocket copayment cost represented a risk for poor adherence to regular prophylaxis. In about two third of the patients, the annual out-of-pocket copayment cost amounted to >50% of their average annual disposable income. Many patients therefore required assistance from the charity assistance projects, but nonadherence remained prevalent. CONCLUSION: Medical insurance policy and charity assistance projects helped haemophilia children to accept and continue prophylaxis regimens. It was the proportion of the out-of-pocket copayment cost rather than the upper limit of insurance reimbursement that restricted long-term regular low-dose prophylaxis in China.