A systematic review of cost-effectiveness analyses of gene therapy for hemophilia type A and B.

BACKGROUND: In 2022-2023, the US Food and Drug Administration approved 2 novel gene therapies, valoctocogene roxaparvovec and etranacogene dezaparavovec, for hemophilia A and B, respectively. These one-time-administered gene therapies have been marketed at prices that create financial challenges for payers and patients. Understanding the magnitude and uncertainties around the long-term value of these therapies and how they can potentially relate to managed care practices is of high interest to the payer and patient community. OBJECTIVE: To conduct a systematic review of cost-effectiveness analysis (CEA) studies to assess (1) the long-term value of valoctocogene roxaparvovec and etranacogene dezaparavovec and (2) the relevance and validity of the underlying data and assumptions used in the CEA models and discuss how they relate to the challenges identified for CEAs of gene therapies. METHODS: A systematic review of cost-effectiveness studies of novel hemophilia A and B gene therapy was conducted. PubMed and Embase were searched for published studies from inception to January 12, 2024. Original research articles published in English that conducted a CEA on gene therapy treatments for hemophilia A and B, with a comparison of incremental costs and health effects, were considered. Critical appraisal of the quality of reporting and the underlying modeling assumptions were conducted to assess the relevance and validity of the results. RESULTS: Two hundred thirty-eight studies were identified, of which 4 met the inclusion criteria. Three studies were conducted from a US health care perspective and 1 from a Dutch societal perspective. Despite the high upfront costs of the gene therapies, all included studies' (3 hemophilia A and 1 hemophilia B) modeled results showed that gene therapies had lower overall costs and better health outcomes compared with factor concentrate replacement therapies and emicizumab. The results were driven by the assumption that gene therapies will have a durable effect of at least 10 years and offset the high cost of the current standard of care. The modeled health improvements varied substantially across studies, showing that the long-term value is sensitive to varying clinical and economic assumptions. CONCLUSIONS: The novel hemophilia gene therapy treatments can potentially be a cost-effective use of treatment resources if the treatment effects are durable over time. To reduce the risk for payers while still facilitating patient access, outcomes-based agreements similar to what has recently been proposed by the Centers for Medicare & Medicaid Services for sickle-cell therapies are well supported.

Optimizing the management of inherited blood disorders in a changing market: Findings from the AMCP Market Insights Program.

In this market insights program, AMCP brought together a panel of experts representing various stakeholders: national and regional health plans, integrated health care systems, employer benefits groups, clinical experts, the Centers for Disease Control and Prevention, and patient advocacy organizations. The objectives were to gain insights into the current and evolving treatments in hemophilia, sickle cell disease, and ß-thalassemia; measure the effects of recently approved therapies on clinicians, payers, and patients; recognize emerging trends within the stop-loss market; address potential issues and obstacles related to monitoring and reporting outcomes; and identify concerns associated with both existing and emerging contracting and reimbursement models. This article aims to summarize expert perspectives on health care system challenges and strategies concerning the management of inherited blood disorders and to advance managed care professionals' understanding of their role in supporting care for these patients. The experts emphasized that when shaping coverage policies, a patient-centered approach is crucial, focusing on preserving organ function to maintain eligibility for future gene therapies among individuals with inherited blood disorders. These strategies, including benefit design modifications, specialized provider networks, and centralized mechanisms like registries, are vital for evaluating effectiveness, facilitating decision-making, and managing costs and risks associated with new and emerging treatment options for inherited blood disorders.

Clinical and economic burden of immune tolerance induction in entire patients with hemophilia A: Insights from a real-world Korean setting.

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.

Health insurance coverage and switching among people with hemophilia A in the United States.

BACKGROUND: Hemophilia A (HA) is marked by substantial economic burden, including costs of ongoing treatment, increased monitoring, bleed events, and other health care utilization associated with managing the disease and comorbidities related to the disease. Gene therapies and other anticipated breakthrough treatments hold potential to substantially offset long-term traditional factor VIII (FVIII) prophylaxis in specific populations. Fragmentation of the US insurance system, however, may impact payers' approaches to coverage of new treatments, given concerns about patients "switching" insurance and the payer's ability to offset costs over time. OBJECTIVE: To assess insurance coverage and switching across payers among people with severe HA (SHA) using real-world data. METHODS: Adult men with SHA (FVIII measuring < 1%) in the American Thrombosis and Hemostasis Network dataset between January 2013 and September 2019 were identified. Patients' primary insurance category (ie, commercial, Medicaid, Medicare) and insurance switching over time were described. Outcomes included distribution of current primary insurance coverage by category and mean years of coverage per payer for commercially insured patients, including those with 2 or more commercial payers, and for those who switched insurance categories (eg, coverage by a commercial payer and government payer). RESULTS: Among the cohort of patients with SHA (N = 3,677), 51.9% had commercial primary insurance and 29.0% had coverage by Medicaid (including state-funded programs). The mean duration of follow-up in the database was 6.3 years for patients with at least 1 year of follow-up. Among patients who had ever been commercially insured, 74.9% had the same commercial payer for the entire follow-up period. The mean time covered by the same commercial insurance was 4.8 years. Only 7.5% of patients switched insurance categories (eg, from commercial to Medicaid). Among those who switched categories, patients averaged 3.9 years of commercial coverage, 4.0 years of Medicaid coverage, and 4.8 years of Medicare coverage during the follow-up period. CONCLUSIONS: Both commercially and government-insured patients with SHA typically maintain continuous coverage for extended periods, with limited switching between payers and insurance categories over time. These findings suggest that should breakthrough treatments be approved, payers would likely be able to realize substantial cost savings associated with avoiding long-term prophylactic therapies during the several years after treatment. DISCLOSURES: This study was funded by BioMarin Pharmaceutical Inc. Hinds, Chen, and Sammon are employees of BioMarin Pharmaceutical Inc. and own stock/stock options. Solari was an employee of BioMarin Pharmaceutical Inc. at the time of the study. Pezalla is CEO of Enlightenment Bioconsult, LLC. He, Cheng, and Recht are, or were at the time of this study, employees of American Thrombosis and Hemostasis Network (ATHN), which has received ATHNdataset licensing and other fees from BioMarin Pharmaceutical Inc. Research funding to Recht's employers has come from Bayer, BioMarin Pharmaceutical Inc., CSL Behring, Genentech, Grifols, Hema Biologics, LFB, Novo Nordisk, Octapharma, Pfizer, Sanofi, Spark, Takeda, and uniQure. Recht has also worked as a consultant for Catalyst Biosciences, CSL Behring, Genentech, Hema Biologics, Kedrion, Novo Nordisk, Pfizer, Sanofi, Takeda, and uniQure; sits on the board of directors of the Foundation for Women and Girls with Blood Disorders and of Partners in Bleeding Disorders; and is an employee of the Oregon Health & Science University. Data from this study were presented as a poster at AMCP Nexus 2021; October 18-21, 2021; Denver, CO.

A comparison between on-demand usage of rFVIIa vs prophylaxis use of emicizumab in high titer inhibitory hemophilia A patients in Iran: A cost-utility analysis.

BACKGROUND: Hemophilia A (HA) is an inherited X-linked bleeding disease with costly treatment, especially for high titer inhibitory patients. Emicizumab, a new humanized bispecific antibody, has been approved for use to prevent or reduce the frequency of bleeding episodes in HA patients with inhibitors. This study evaluated the cost-utility of emicizumab prophylaxis (EP) in comparison with recombinant factor VII activated on-demand treatment in HA patients with inhibitors. METHODS: A life-time Markov model with payer and societal perspectives was developed in different age groups with different annual bleeding rates (ABR). Efficacy of treatments were extracted from HAVEN trials. Utilities were retrieved from published evidence. Costs were calculated based on Iran food and drug administration official website, national tariff book for medical services and hospital data. One-way deterministic sensitivity analysis was performed. RESULTS: EP was dominant choice in comparison with on-demand administration of recombinant factor VII activated in all age groups with ABR 20 and 25, and it remained dominant in patients with age 2 and age 12 at start point with ABR 16 and 17. The reported incremental cost-effectiveness ratio for the group with ABR 18 at the age 20, was 12,936 United States Dollars which is lower than the acceptable threshold of cost-effectiveness in Iran (1-3 gross domestic product per capita) and EP can be considered as cost-effective choice in this scenario. CONCLUSION: EP was found to be a dominant and cost-effective choice for Iranian HA patients with factor VIII inhibitors with ABR 18 and above with considerable cost saving.

Does Cost-Effectiveness Analysis Overvalue Potential Cures? Exploring Alternative Methods for Applying a "Shared Savings" Approach to Cost Offsets.

OBJECTIVES: To evaluate alternative methods to calculate and/or attribute economic surplus in the cost-effectiveness analysis of single or short-term therapies. METHODS: We performed a systematic literature review of articles describing alternative methods for cost-effectiveness analysis of potentially curative therapies whose assessment using traditional methods may suggest unaffordable valuations owing to the magnitude of estimated long-term quality-adjusted life-year (QALY) gains or cost offsets. Through internal deliberation and discussion with staff at the Health Technology Assessment bodies in England and Canada, we developed the following 3 alternative methods for further evaluation: (1) capping annual costs in the comparator arm at $150 000 per year; (2) "sharing" the economic surplus with the health sector by apportioning only 50% of cost offsets or 50% of cost offsets and QALY gains to the value of the therapy; and (3) crediting the therapy with only 12 years of the average annual cost offsets or cost offsets and QALY gains over the lifetime horizon. The impact of each alternative method was evaluated by applying it in an economic model of 3 hypothetical condition-treatment scenarios meant to reflect a diversity of chronicity and background healthcare costs. RESULTS: The alternative with greatest impact on threshold price for the fatal pediatric condition spinal muscular atrophy type 1 was the 12-year cutoff scenario. For a hypothetical one-time treatment for hemophilia A, capping cost offsets at $150 000 per year had the greatest impact. For chimeric antigen receptor T-cell treatment of non-Hodgkin's lymphoma, capping cost offsets or using 12-year threshold had little impact, whereas 50% sharing of surplus including QALY gains and cost offsets greatly reduced threshold pricing. CONCLUSIONS: Health Technology Assessment bodies and policy makers will wrestle with how to evaluate single or short-term potentially curative therapies and establish pricing and payment mechanisms to ensure sustainability. Scenario analyses using alternative methods for calculating and apportioning economic surplus can provide starkly different assessment results. These methods may stimulate important societal dialogue on fair pricing for these novel treatments.

Variability of treatment modalities and intensity in patients with severe haemophilia A on prophylaxis: Results from the Italian national registry.

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.

Real-world analysis of haemophilia patients in China: A single centre's experience.

INTRODUCTION: The management of haemophilia is critical to minimize the risk of disability and reduce the burden on China's healthcare system. AIM: This study was based on a single centre in China and was conducted to understand the evolution of real-world haemophilia care over the past 15 years. METHODS: We retrospectively analysed clinical characteristics, diagnosis, treatment and medical expenditures of 428 patients with haemophilia from January 2004 to December 2018 from the Institute of Hematology & Blood Diseases Hospital in Tianjin, China. RESULTS: The delayed diagnosis time significantly decreased from 13.3 ± 5.1 years before 2004 to 0.4 ± 0.4 year in 2014-2018 (P < .05). Among children and adults receiving prophylactic treatment, the annual factor consumption increased from 2004-2008 (168.8 IU/kg in children and 120.7 IU/kg in adults) to 2009-2013 (389.2 IU/kg in children and 316.2 IU/kg in adults) and 2014-2018 (1328.0 IU/kg in children and 878.8 IU/kg in adults, P < .001). The annual medical insurance expenditure for haemophilia had increased steadily over the past 10 years. The number of patients tested regularly for inhibitors increased from 2004 (1.9% [2/105]) to 2018 (21.5% [59/275]). The seroprevalence of hepatitis C virus (HCV) was 33.8% during the years examined, while the incidence rates of HCV among patients significantly decreased (7.3% in 2008 to 0.4% in 2018). CONCLUSION: Significant improvements in the management of haemophilia were observed from 2004 to 2018. These results highlight the joint effort of the reimbursement policy and drug regulatory management paving the way for a better future for patients with haemophilia in China.

Model of Short- and Long-Term Outcomes of Emicizumab Prophylaxis Treatment for Persons with Hemophilia A.

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.

Economic burden of hemophilia A and B: a case in Iran.

Objective: To estimate the economic burden of hemophilia A and B in the patients referred to the related referral hospital in the south of Iran in 2017.Methods: This cross-sectional study was a partial economic evaluation and a cost of illness study, carried out in 2017. All the patients with hemophilia A and B referred to the related hospital affiliated to Shiraz University of Medical Sciences in the south of Iran were included in the study (N = n = 253). A data collection form was used to collect the required data, including patients' direct and indirect costs.Results: The mean annual cost was 36028 USD. The mean costs per patient with hemophilia A and B were 37661 USD and 30775 USD, respectively, in which the greatest part were related to direct medical costs (98.32% in hemophilia A, 98.18% in hemophilia B, and 98.29% of the total costs), and the cost of clotting factor concentrates accounted for the largest share of the patients' direct medical costs. Also, considering the number of hemophilia patients in Iran, the mean annual cost of the patients in 2017 was 414480325 USD, of which 381503701 USD was for hemophilia A and 32976624 USD was for hemophilia B patients.Conclusion: Considering the significant economic burden of hemophilia and in order to reduce the costs, the following suggestions can be offered: provision of clotting factor concentrates domestically in accordance with the world standards, and providing specialized services and care to hemophilia patients in towns.

Cost-utility analysis of factor VIII diet therapies prepared using blood plasma vs. recombinant technique for patients with hemophilia A.

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.

Comparing Factor Use and Bleed Rates in U.S. Hemophilia A Patients Receiving Prophylaxis with 3 Different Long-Acting Recombinant Factor VIII Products.

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.

The cost of hemophilia treatment: the importance of minimizing it without detriment to its quality.

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.

Cost-Effectiveness and Budget Impact of Emicizumab Prophylaxis in Haemophilia A Patients with Inhibitors.

Recent evidence demonstrated that weekly prophylaxis with subcutaneous bispecific antibody (emicizumab) has shown higher efficacy in adolescent and adults patients affected by haemophilia A (HA) with inhibitor, compared with patients treated on demand or on prophylaxis with bypassing agents (BPAs). However, no economic evaluations assessing the value and sustainability of emicizumab prophylaxis have been performed in Europe. This study assessed the cost-effectiveness of emicizumab prophylaxis compared with BPA prophylaxis and its possible budget impact from the Italian National Health Service (NHS) perspective. A Markov model and a budget impact model were developed to estimate the cost-effectiveness and budget impact of emicizumab prophylaxis in HA patients with inhibitors. The model was populated using treatment efficacy from clinical trials and key clinical, cost and epidemiological data retrieved through an extensive literature review. Compared with BPAs prophylaxis, emicizumab prophylaxis was found to be more effective (0.94 quality adjusted life-years) and cost saving (-€19.4/-€24.4 million per patient lifetime) in a cohort of 4-year-old patients with HA and inhibitors who failed immune tolerance induction. In the probabilistic sensitivity analysis, emicizumab prophylaxis had always 100% probability of being cost-effective at any threshold. Further, the use of emicizumab prophylaxis was associated to an overall budget reduction of €45.4 million in the next 3 years. In conclusion, the clinically effective emicizumab prophylaxis can be considered a cost-saving treatment for HA with inhibitor patients. Furthermore, emicizumab treatment is also associated to a significant reduction of the health care budget, making this new treatment a sustainable and convenient health care option for Italian NHS.

Optimising prophylaxis outcomes and costs in haemophilia patients switching to recombinant FVIII-Fc: a single-centre real-world experience.

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.

Positive emotions despite substantial burden: The alchemy of haemophilia caregiving.

INTRODUCTION: Qualitative interviews when developing the haemophilia caregiver impact measure© (HCI) documented the importance of capturing the positive aspects of caregiving, not just the negative. AIM: The present study thus investigates the construct underlying the positive emotions HCI subscale and tests models proposing a more comprehensive way of thinking about this construct. METHODS: Secondary analysis was implemented on longitudinal web-based survey data (n = 323) from haemophilia A or haemophilia B caregivers. Person-reported outcomes (PROs) included the HCI, the PROMIS-10 and Ryff psychological well-being subscales. Predictors included caregiver demographics; patient haemophilia characteristics; exercise; adherence; and quality-of-life (QOL) appraisal processes as measured by the brief appraisal inventory (BAI) which yields composite scores assessing awareness of challenges, fulfillment and growth, stay positive, social comparison and interpersonal problem-solving. Second-order factor analysis, structural equation modelling and residual modelling were implemented. RESULTS: A structural equation model fit the data well that contained bifactor representation of well-being with a general factor comprised of environmental mastery, positive relations with others, physical functioning and emotional functioning. Positive emotions was modelled as a component of well-being, with a unique component ('Alchemy') characterized by its associations with stay positive, and awareness of challenges appraisals, and difficulty paying bills. Alchemy had positive linear relationships with the first two, and a positive quadratic relationship with difficulty paying bills. CONCLUSIONS: Adopting positive-focused ways of thinking about one's life limitations may transform the negatives of haemophilia caregiving into something positive. Such cognitive habits reflect an awareness and acceptance of the limitations imposed by haemophilia caregiving.