Analysis of long-term clinical and cost impact of etranacogene dezaparvovec for the treatment of hemophilia B population in the United States.

INTRODUCTION: Etranacogene dezaparvovec (EDZ), Hemgenix, is a gene therapy recently approved for people with hemophilia B (PwHB). OBJECTIVE: To estimate long-term clinical impact and cost of EDZ in the United States (US). METHODS: A decision-analytic model was developed to evaluate the long-term impact of introducing EDZ for PwHB over a 20-year time horizon. Factor IX (FIX) prophylaxis comparator was a weighted average of different FIX prophylaxis regimens based on US market share data. We compared a scenario in which EDZ is introduced in the US versus a scenario without EDZ. Clinical inputs (annualized FIX-treated bleed rate; adverse event rates) were obtained from HOPE-B phase 3 trial. EDZ durability input was sourced from an analysis predicting long-term FIX activity with EDZ. EDZ one-time price was assumed at $3.5 million. Other medical costs, including FIX prophylaxis, disease monitoring, bleed management, and adverse events were from literature. The model estimated annual and cumulative costs, treated bleeds, and joint procedures over 20 years from EDZ introduction. RESULTS: Approximately 596 PwHB were eligible for EDZ. EDZ uptake was estimated to avert 11,282 bleeds and 64 joint procedures over 20 years. Although adopting EDZ resulted in an annual excess cost over years 1-5 (mean: $53 million annually, total $265 million), annual cost savings were achieved beginning in year 6 (mean: $172 million annually; total $2.58 billion in years 6-20). The total cumulative 20-year cost savings was $2.32 billion, with cumulative cost savings beginning in year 8. CONCLUSION: Introducing EDZ to treat PwHB is expected to result in cost savings and patient benefit over 20 years. Initiating PwHB on EDZ sooner can produce greater and earlier savings and additional bleeds avoided. These results may be a conservative estimate of the full value of EDZ, as PwHB would continue to accrue savings beyond 20 years.

This analysis assessed the long-term clinical and financial impact of introducing EDZ in the United States of America for people with severe or moderately severe hemophilia B. A decision-analytic model was developed comparing a scenario with EDZ and one without EDZ over 20 years. Introducing EDZ would avert 11,292 bleeds and 64 joint procedures over 20 years and would achieve cumulative cost savings in year 8, with a total cumulative 20-year cost saving of $2.32 billion.

Cost-Effectiveness of Recombinant Factor IX Fc Prophylaxis and Recombinant Factor IX On-Demand Treatment in Patients with Haemophilia B Without Inhibitors.

INTRODUCTION: Recombinant factor IX (rFIX) and recombinant FIX Fc fusion protein (rFIXFc) are standard half-life and extended half-life FIX replacement therapies, respectively, and represent established treatment options indicated for adults and children with haemophilia B. These FIX replacement therapies can be administered as prophylaxis (to prevent bleeding) or 'on-demand' (to stop bleeding). This analysis aimed to estimate the cost-effectiveness of once-weekly prophylaxis with rFIXFc versus on-demand treatment with rFIX in patients with haemophilia B without inhibitors in the Italian healthcare setting. METHODS: A Markov model was developed to assess a hypothetical cohort of adolescent or adult male patients (≥ 12 years) with haemophilia B (FIX level of ≤ 2 IU/dL) without inhibitors. Model inputs were derived from the pivotal phase 3 clinical studies for rFIXFc and rFIX, published literature and assumptions when published data were unavailable. The model employed a lifelong time horizon with 6-monthly transitions between health states, and it estimated total costs, total quality-adjusted life years (QALYs), number of bleeds, number of surgeries and incremental cost-effectiveness ratio. RESULTS: rFIXFc prophylaxis was associated with lower total costs per patient (€5,308,625 versus €6,564,510) and greater total QALYs per patient (15.936 versus 11.943) compared with rFIX on-demand; rFIXFc prophylaxis was therefore the dominant treatment strategy. The model also demonstrated that rFIXFc prophylaxis was associated with fewer incremental bleeds (- 682.29) and surgeries (- 0.39) compared with rFIX on-demand. CONCLUSIONS: rFIXFc prophylaxis provides improved health outcomes and lower costs, and represents a cost-effective treatment option compared with rFIX on-demand for adolescent and adult male patients with haemophilia B. This comparative assessment of cost-effectiveness should help to inform both clinicians and healthcare policy makers when making treatment decisions for patients with haemophilia B.

The cost-effectiveness of gene therapy for severe hemophilia B: a microsimulation study from the United States perspective.

Adeno-associated virus (AAV)-mediated gene therapy is a novel treatment promising to reduce morbidity associated with hemophilia. Although multiple clinical trials continue to evaluate efficacy and safety, limited cost-effectiveness data have been published. This study compared the potential cost-effectiveness of AAV-mediated factor IX (FIX)-Padua gene therapy for patients with severe hemophilia B in the United States vs on-demand FIX replacement and primary FIX prophylaxis, using either standard or extended half-life FIX products. A microsimulation Markov model was constructed, and transition probabilities between health states and utilities were informed by using published data. Costs were aggregated by using a microcosting approach. A time horizon from 18 years old until death, from the perspective of a third-party payer in the United States, was conducted. Gene therapy was more cost-effective than both alternatives considering a $150 000/quality-adjusted life-year threshold. The price for gene therapy was assumed to be $2 000 000 in the base case scenario; however, one of the 1-way sensitivity analyses was conducted by using observed manufacturing, administration, and 5-year follow-up costs of $87 198 for AAV-mediated gene therapy vector as derived from the manufacturing facility and clinical practice at St Jude Children's Research Hospital. One-way sensitivity analyses revealed 10 of 102 scenarios in which gene therapy was not cost-effective compared with alternative treatments. Notably, gene therapy remained cost-effective in a hypothetical scenario in which we estimated that the discounted factor concentrate price was 20% of the wholesale acquisition cost in the United States. Probabilistic sensitivity analysis estimated gene therapy to be cost-effective at 92% of simulations considering a $150 000/quality-adjusted life-year threshold. In conclusion, based on detailed simulation inputs and assumptions, gene therapy was more cost-effective than on-demand treatment and prophylaxis for patients with severe hemophilia B.

Clinical, pharmacokinetic and economic analysis of the first switch to an extended half-life factor IX (albutrepenonacog alfa, rFIX-FP) in Spain.

Extended half-life of factor IX (FIX) demonstrated clinical benefit and lower treatment burden than standard half-life FIX products in clinical trials. We analysed the impact in efficacy, pharmacokinetics (PKs) and costs of the switch from nonacog alfa (rFIX) to albutrepenonacog alfa (rFIX-FP) in the first patient with haemophilia B (HB) treated in Spain outside clinical trials. A 7-year-old boy presented with HB with poor venous access and repetition infections using rFIX, which was switched to rFIX-FP. Prophylaxis was adjusted by PKs using WAPPS-Hemo tailoring from 100 IU/kg/week of rFIX to 80 IU/kg/3 weeks of rFIX-FP. Comparing 6 months before, rFIX-FP reduced 68.5% FIX consumption/kg and 58.3% infusion frequency, but total costs/weight showed a slight increase. Ratio of half-life between rFIX and rFIX-FP was 3.4-3.7. This case report revealed that switch to rFIX-FP decreased frequency and FIX consumption, without adverse events and bleeds.

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.

Hemophilia Burden of Disease: A Systematic Review of the Cost-Utility Literature for Hemophilia.

BACKGROUND: Prophylaxis with clotting factor replacement products is recommended by the Medical and Scientific Advisory Council of the National Hemophilia Foundation as the optimal therapy for the prevention of bleeding episodes in individuals with severe hemophilia A or B (< 1 IU per dL endogenous factor VIII or factor IX activity, respectively). Prophylaxis is associated with an improved health-related quality of life and has been shown to be cost-effective compared with on-demand therapy. However, the overall cost of treatment remains high, particularly among patients with a greater propensity to bleed. The overall value of hemophilia treatments and their associated benefits, measured in quality-adjusted life-years (QALYs), and dollar costs compared with other interventions can be evaluated through the use of cost-utility analyses (CUAs). Previous CUA studies in hemophilia have focused primarily on patients with more severe forms of hemophilia and on prophylaxis compared with on-demand treatment. However, to our knowledge, no studies to date have utilized QALYs as a standardized outcome measure to systematically evaluate the relative cost-effectiveness of current hemophilia treatment options. OBJECTIVE: To systematically review the CUA literature of hemophilia treatments and demonstrate the challenges in producing cost-utility evidence compared with other rare diseases. METHODS: We conducted a systematic literature review using the Tufts Medical Center Cost-Effectiveness Analysis Registry and the National Health Service Economic Evaluation Database for English-language CUAs published from 2000 through 2015 with the search terms hemophilia, haemophilia, factor VIII, or factor IX. Two trained reviewers independently reviewed every study to extract relevant data. Incremental cost-effectiveness ratios were converted to 2014 U.S. dollars using exchange rates for currency conversion and the Consumer Price Index to adjust for inflation. RESULTS: Our search yielded 52 studies, 11 of which met our inclusion criteria. The cost-effectiveness of hemophilia treatments varied widely based on variations in the study designs, including differences in time horizon, discount rates, and medical interventions. CONCLUSIONS: We found the cost-effectiveness of hemophilia treatments to be broadly comparable to that of other orphan drugs. Improved standardization of future CUA studies will be important for further evaluation of the cost-effectiveness of hemophilia treatments. DISCLOSURES: This research was funded by Biogen, which provided an unrestricted research grant to the Center for the Evaluation of Value and Risk in Health at Tufts Medical Center. Biogen and Sobi reviewed and provided feedback on the manuscript. The authors had full editorial control of the manuscript and provided final approval of all content. The authors report no conflict of interest regarding the material discussed in this article. Neumann and Chambers are employed at the Center for the Evaluation of Value and Risk in Health at Tufts Medical Center. Thorat was an employee of Center for Evaluation Value and Risk in Health, Tufts Medical Center when the analyses were carried out. Chambers has participated on advisory boards for Sanofi and Astellas Pharma.

The Jamaican Haemophilia Registry: Describing the burden of disease.

INTRODUCTION: Jamaica has an estimated 200 persons with haemophilia (PWH), who face significant constraints in access to specialized haemophilia care, including access to clotting factor concentrates. AIM: The aim of this paper is to establish the current burden of disease in PWH in Jamaica. METHODS: PWH were enrolled through the University Hospital of the West Indies, Jamaica. The impact of haemophilia was assessed using a comprehensive battery of heath outcome measures that included the following: laboratory, clinical information and validated outcome measures of joint structure and function, activity, and health-related quality of life (HRQoL) to provide a health profile of the Jamaican haemophilia population. RESULTS: In all, 45 PWH were registered (mean age: 29, range: 0.17-69 years), including 13 children (<18 years of age) and 32 adults. In this sample, 41 had haemophilia A (30 severe) and 4 had haemophilia B (3 severe); 10 patients with haemophilia A were inhibitor positive. The results indicate that adults with haemophilia in Jamaica have significant joint damage: mean Haemophilia Joint Health Score (HJHS) = 42.1 (SD = 17.3); moderate activity levels - mean Haemophilia Activities List (HAL) score = 64.8 (SD = 17.8); and low HRQoL scores - mean Haemo-QoL-A score = 62.3 (SD = 19.4). Results for children are also reported but should be interpreted with caution due to the small sample size. CONCLUSIONS: There is a very high burden of disease in PWH in Jamaica. The health profiles reported in this paper are an essential first step in advocating for a multidisciplinary Comprehensive Care Program for assessment and care of PWH in Jamaica.

Real-World Analysis of Dispensed IUs of Coagulation Factor IX and Resultant Expenditures in Hemophilia B Patients Receiving Standard Half-Life Versus Extended Half-Life Products and Those Switching from Standard Half-Life to Extended Half-Life Products.

BACKGROUND: Hemophilia B requires replacement therapy with factor IX (FIX) coagulation products to treat and prevent bleeding episodes. A recently introduced extended half-life (EHL) recombinant FIX replacement product provided the opportunity to compare the amount of dispensed factor and expenditures for EHL treatment compared with a standard half-life (SHL) product. OBJECTIVE: To determine factor international units (IUs) dispensed and expenditures associated with switching from nonacog alfa, the most commonly used SHL replacement product, to eftrenonacog alfa, an EHL FIX replacement product. METHODS: Two U.S. claims databases were analyzed. A large national specialty pharmacy dispensation claims database was used to identify the number of IUs dispensed and monthly charges for all patients with hemophilia B from April 2015 to June 2016. Truven Health MarketScan Research Databases (January 2010-July 2016) were used to identify IUs and expenditures for patients with claims data for at least 3 months before and after switching from the SHL to the EHL product. Medians for IUs and expenditures are presented to accommodate for skewness of data distribution. RESULTS: The national specialty pharmacy database analysis included 296 patients with moderate or severe hemophilia B (233 on SHL; 94 on EHL). Median monthly factor dispensed was 11% lower (2,142 IU) in the EHL versus SHL cohort over the study period, while individual monthly reductions ranged from 32% to 47% (9,838 IU to 16,514 IU). Using the wholesale acquisition cost, the median per-patient monthly factor expenditures over the 15-month study period were 94% higher ($23,005) for the EHL than for the SHL product. Individual median monthly expenditure differences ranged from 15% ($6,562) to 49% ($19,624). In the Truven database, 14 patients switched from the SHL to the EHL product. The amount of factor dispensed was variable; in the 1-year period before and after the switch from the SHL to the EHL product, mean IUs dispensed decreased by 3,005 IU, while median IUs dispensed increased by 4,775 IU. Factor replacement expenditures were higher after switching from the SHL to the EHL product in each of the 3-month periods examined before versus after the switch. CONCLUSIONS: This analysis of real-world data showed that switching from the SHL to the EHL product was associated with higher expenditures. Increased expenditures noted in the first 3 months after switching may be related to initial stocking up of the EHL product, but expenditures were sustained throughout the 1-year period of data analysis. Further analysis of these findings with larger numbers of patients should be explored. DISCLOSURES: This study was sponsored by Pfizer. Pfizer employees were involved in the study design; the collection, analysis, and interpretation of data; the review of the manuscript; and the decision to submit for publication. All authors are employees of Pfizer. No author received an honorarium or other form of payment related to the development of this manuscript. All authors participated in the study design, data interpretation, and manuscript review and revisions and granted approval for the submission of the manuscript. Alvir, McDonald, and Tortella also participated in data analysis. Data from this paper were presented in part at the European Association for Haemophilia and Allied Disorders Annual Meeting, February 1-3, 2017, Paris, France; at the International Society for Pharmacoeconomics and Outcomes Research Annual Meeting, May 20-24, 2017, Boston, MA; and at the International Society on Thrombosis and Haemostasis Congress, July 8-13, 2017, Berlin, Germany.

Modern Treatments of Haemophilia: Review of Cost-Effectiveness Analyses and Future Directions.

BACKGROUND: Cost is currently one of the most important aspects in haemophilia care. Factor concentrates absorb more than 90% of healthcare direct costs of haemophilia care, and the debate regarding the high cost of haemophilia treatments and their different use across different countries is increasing. OBJECTIVE: The objective of this study was to review cost-effectiveness analyses conducted on treatment options in haemophilia, focusing on their results and their strengths and limitations; to highlight the possible issues associated with economic evaluations of new treatment options. METHODS: Electronic searches in PubMed and EMBASE were performed to retrieve papers published between November 2015 and September 2017 to update the previous review of economic evaluations of haemophilia treatments by Drummond et al. Reference lists of included articles and reviews were examined for relevant studies, which were assessed for their quality and their empirical results. RESULTS: Twenty-six relevant economic analyses were identified; 15 (57.7%) were conducted in patients with haemophilia with inhibitors while 11 (42.3%) involved patients without inhibitors. There were methodological variations among the included studies, and differences in the treatment schemes make a comparative assessment of interventions for patients with haemophilia difficult. Only immune tolerance induction showed consistent results in its cost-saving profile compared with the treatment with bypassing agents. CONCLUSIONS: Economic evaluations of haemophilia treatments are increasing, but the identification of general cost-effectiveness trends is still difficult in these studies. We are now facing a new era in haemophilia management with a soaring need for high-quality economic evaluations, performed through proactive collaboration between clinical experts, budget holders and health economists.

Economic Burden of Illness among Persons with Hemophilia B from HUGS Vb: Examining the Association of Severity and Treatment Regimens with Costs and Annual Bleed Rates.

OBJECTIVES: To determine US societal burden of illness, including direct and indirect costs and annual bleed rate (ABR), for persons with hemophilia B (HB), a rare and debilitating genetic disorder, and to examine associations of hemophilia severity and treatment regimens with costs and ABR. METHODS: From 2009 to 2014, the Hemophilia Utilization Group Studies Part Vb collected prospective data from 10 US hemophilia treatment centers. Participants with HB completed initial surveys on sociodemographic characteristics, clinical characteristics, and treatment patterns. During the 2-year follow-up, participants reported bleeding episodes, work absenteeism, and caregiver time quarterly. These data were used to calculate ABR and indirect costs. Direct costs were calculated using 1-year clinical chart records and 2-year dispensing records. RESULTS: Of the 148 participants, 112 with complete medical records and one or more follow-up survey were included. Total mean annual per-person costs were $85,852 (median $20,160) for mild/moderate HB, $198,733 (median $147,891) for severe HB, and $140,240 (median $63,617) for all participants without inhibitors (P < 0.0001). Mean ABR for participants with severe HB on prophylaxis (5.5 ± 7.9 bleeds/y) was almost half that of those treated episodically. Clotting factor and indirect costs accounted for 85% and 9% of total costs, respectively. Compared with episodic treatment, prophylaxis use was associated with 2.5-fold higher clotting factor costs (P < 0.01), low but significantly more missed parental workdays (P < 0.0001) and clinician (P < 0.001) or nursing visits (P < 0.0001), less part-time employment and unemployment, and lower hospitalizations costs (P = 0.17) and ABR (P < 0.0001). CONCLUSIONS: HB is associated with high economic burden, primarily because of clotting factor costs. Nevertheless, prophylaxis treatment leads to clinical benefits and may reduce other nonfactor costs.

Hemophilia and inhibitors: current treatment options and potential new therapeutic approaches.

The immune response to infused factor concentrates remains a major source of morbidity and mortality in the treatment of patients with hemophilia A and B. This review focuses on current treatment options and novel therapies currently in clinical trials. After a brief review of immune tolerance regimens, the focus of the discussion is on preventing bleeding in patients with hemophilia and inhibitors. Recombinant factor VIIa and activated prothrombin complex concentrates are the mainstays in treating bleeds in patients with inhibitors. Both agents have been shown to reduce bleeding episodes to a similar degree when infused prophylactically; however, individual patients may respond better to one agent over the other at any given time. The international immune tolerance trial revealed that a high-dose factor VIII regimen provided significantly better bleeding protection than the low-dose regimen. Given the high cost of treatment and the potential for a high-dose immune tolerance regimen to prevent bleeding in some patients, we discuss how we treat patients to maximize the prevention of bleeds while minimizing cost. Novel approaches to treatment of these patients are in development. These include agents that mimic factor VIII or augment thrombin generation by bypassing the inhibitor, as well as agents that inhibit the natural anticoagulants.

A Budget Impact Model of Hemophilia Bypassing Agent Prophylaxis Relative to Recombinant Factor VIIa On-Demand.

BACKGROUND: Hemophilia patients use factor-clotting concentrates (factor VIII for hemophilia A and factor IX for hemophilia B) for improved blood clotting. These products are used to prevent or stop bleeding episodes. However, some hemophilia patients develop inhibitors (i.e., the patient's immune system develops antibodies against these factor concentrates). Hence, these patients do not respond well to the factor concentrates. A majority of hemophilia patients with inhibitors are managed on-demand with the following bypassing agents: recombinant factor VIIa (rFVIIa) and activated prothrombin complex concentrate (aPCC). The recently published U.S. registries Dosing Observational Study in Hemophilia (DOSE) and Hemostasis and Thrombosis Research Society (HTRS) reported higher rFVIIa on-demand use for bleed management than previously described. OBJECTIVE: To estimate aPCC and rFVIIa prophylaxis costs relative to rFVIIa on-demand treatment cost based on rFVIIa doses reported in U.S. registries. METHODS: A literature-based cost model was developed assuming a base case on-demand annual bleed rate (ABR) of 28.7 per inhibitor patient, which was taken from a randomized phase 3 clinical trial. The doses for rFVIIa on-demand were taken from the median dose per bleed reported by the DOSE and HTRS registries. Model inputs for aPCC and rFVIIa prophylaxis (i.e., dosing and efficacy) were derived from respective randomized clinical trials. Cost analysis was from the U.S. payer perspective, and only direct drug costs were considered. The drug cost was based on the Medicare Part B 2014 average sale price (ASP). Two-way sensitivity and threshold analyses were performed by simultaneously varying on-demand ABR, prophylaxis efficacy, and unit drug cost. In addition to studying relative costs associated with on-demand and prophylaxis treatments, relative cost per bleeding episode avoided were also calculated for aPCC and rFVIIa prophylaxis treatments. The prophylaxis efficacy reported in the trials were used to determine the number of bleeding episodes avoided. RESULTS: Based on the median on-demand dose of 695 mcg per kg per bleed, reported by the DOSE registry, the annual rFVIIa on-demand cost was $34,009 per kg of body weight. The annual rFVIIa on-demand cost was $22,020 per kg of body weight when the median dose of 450 mcg per kg per bleed reported by the HTRS registry was considered. The annual cost rose to $38,461 per kg of body weight when the rFVIIa on-demand dose of 786 mcg per kg per bleed among patients infusing an initial dose ≥ 250 mcg per kg was considered. The aPCC (85 units per kg per every other day) and rFVIIa (90 mcg per kg per every day) annual prophylaxis costs were $26,536 and $60,700, respectively. Also, aPCC and rFVIIa prophyaxis treatments were estimated to prevent a total of 20.8 and 12.9 annual bleeding episodes, respectively. When compared with the on-demand dose of 695 mcg per kg per bleed (DOSE registry), the annual aPCC and rFVIIa prophylaxis costs were 21.9% lower and 78.4% higher, respectively. Additionally, aPCC prophylaxis saved $360 per kg for each bleeding episode avoided. rFVIIa prophylaxis cost $2,066 per kg for each bleeding episode avoided. Compared with the on-demand dose of 450 mcg per kg per bleed (HTRS registry), aPCC and rFVIIa prophylaxis costs were 20.5% and 174.9% higher, respectively. In this case, aPCC and rFVIIa prophylaxis treatment costs were $217 per kg and $2,995 per kg, respectively, for each bleeding episode avoided. aPCC and rFVIIa prophylaxis costs were 31.0% lower and 57.8% higher, respectively, when compared with the rFVIIa on-demand dose of 786 mcg per kg per bleed, among patients infusing an initial dose ≥ 250 mcg per kg (HTRS registry). In this case, aPCC prophylaxis saved $573 per kg for each bleeding episode avoided, while rFVIIa prophylaxis costs $1,724 per kg for each bleeding episode avoided. Results of the 2-way sensitivity analyses were robust in the majority of the scenarios considered. CONCLUSIONS: aPCC prophylaxis may be cost saving for managing hemophilia patients with inhibitors who bleed frequently and infuse significant quantities of rFVIIa on-demand.

[Economic impact of hemophilia type A and B in Mexico]. / Impacto económico de la hemofilia tipo A y B en México.

BACKGROUND: The treatment of hemophilia generates a disproportionally large economic impact relative to its prevalence. OBJECTIVE: To determine the economic impact of hemophilia A and B in Mexico in 2011 from the perspective of public health institutions. METHODS: Hemophilia was epidemiologically characterized in Mexico during the year of interest, direct costs (diagnosis, monitoring or follow-up, care of bleeding events, and consumption of hemostatic factors), as well as absenteeism associated with illness (indirect costs) were estimated. Records, surveys and official data were supplemented by expert opinion to assess costs. RESULTS: The investment in hemostatic factors is the primary source of cost: 68.6 and 74.3% of total investment in hemophilia A and B, respectively. Sensitivity analysis showed that the most decisive variable is the cost of acquisition of hemostatic factors, including bypass agents. The second most important source of cost is the attention to bleeding events, being significantly higher in patients receiving on-demand treatment compared with those receiving prophylaxis. CONCLUSION: In Mexico, hemophilia is a condition whose treatment requires a large amount of financial resources associated with the cost of hemostatic factors and care of hemorrhage, the latter being lower in patients on prophylaxis relative to on-demand.

Health care resource utilization and cost of care for haemophilia A and B patients in Iran.

BACKGROUND: Despite the fact that the total therapeutic expenditure of haemophilia is paid by the national health system in Iran, a limited number of research has been performed to evaluate the economic burden of haemophilia. It is even more important when considering the fact that "prophylaxis" has never been used as the main treatment protocol in haemophiliacs in the country, causing high arthropathy rates. The aim of this study is to evaluate the cost drivers in the treatment of haemophilia A and B patients in Iran. METHODS: The national registry database of Ministry of Health (MoH) was queried to identify total number of individuals characteristics diagnosed with Factor VIII and IX deficiency. The service package defined by the department for special diseases was used as the reference for the type and frequency of health care utilization in haemophiliacs in Iran. The direct medical costs including prescription, medical intervention, inpatient, outpatient and diagnostics services and arthroplasty were considered. The prices were extracted from Iranian medical tariff book 2014-15. Medication cost was obtained from the Iranian Food and Drug Organization. RESULTS: Among 8,337 patients registered with bleeding disorders, 3,948 and 848 were identified with haemophilia A and B respectively, of whom 856 (18%) patients had inhibitor at any time in the past. In the two groups, 2,328 (59%) and 452 (53%) patients suffered from severe, 686 (17%) and 186 (22%) from moderate and 902 (23%) and 185 (22%) from mild type of haemophilia. The average annual health care cost for every patient was USD 15,130, mostly allocated to medication USD 10,180 (67%), followed by therapeutic services USD 4,775 (32%) while diagnostic services stood third USD 177 (1%). CONCLUSIONS: There is an urgent need for developing clinical practice guidelines for treatment protocols, procedures and supportive care in haemophilia management in Iran.

The long and short of it: using the new factor products.

Hemophilia A (HA) and B (HB) are classified as mild (>5%-40%) moderate (1%-5%) and severe (<1%) disease based on plasma factor activity. Severity of bleeding is commensurate with baseline factor levels in general; however, heterogeneity of bleeding in patients is well described. Recurrent bleeding with painful and disabling musculoskeletal complications is the largest source of morbidity for persons with hemophilia (PWH) but treatment advances through the years has led to improved outcomes. In the early 20(th) century, only whole blood and fresh frozen plasma (FFP) was available to treat bleeding episodes. In 1959, cryoprecipitate was discovered and became an option for treatment of HA in 1965. In the 1970s plasma fractionation led to the first standard half-life (SHL) concentrates. These products ushered in the use prophylactic therapy to prevent bleeding episodes. However, viral contamination slowed the use of prophylaxis until the 1980s when viral attenuation steps increased the safety of plasma concentrates. In the 1990s recombinant concentrates were developed and prophylactic therapy is increasing widely yet not yet universally used. However even with frequent SHL concentrate infusions outcomes are not optimal as PWH spend the majority of time with factor levels below the normal range and are at increased risk for bleeding. In 2014, the first extended half-life (EHL) products were approved for use and have begun to change the landscape of hemophilia care. Challenges of EHL implementation include patient selection, product selection, dose and schedule of infusions, monitoring for safety, efficacy and outcomes, and managing economic aspects of care.

Costs and utilization of treatment in patients with hemophilia.

BACKGROUND: Although hemophilia has a potentially high economic impact, there are no published estimates of healthcare costs for this disease in Portugal. The aim of this study was to evaluate costs of treatment and hospital utilization among patients with hemophilia A and B, with and without inhibitors, over a 3-year period in a Portuguese Comprehensive Care Hemophilia Centre. This is the first study on the financial impact of healthcare costs in patients with hemophilia in Portugal. METHODS: This retrospective, observational study identified patients diagnosed with hemophilia A and B using medical and pharmacy electronic medical records and data from Centro Hospitalar São João, between January 2011 and December 2013. Patients with inhibitors were all high responders (>5 Bethesda Units [BU]). Severity was classified as mild, moderate or severe based on clotting factor levels. Two main outcomes were measured: (1) cost associated with hospital pharmacy claims (clotting factor) and (2) number of hospital visits/hospitalization. RESULTS: A cohort of 103 patients were identified: 72 (69.9 %) with hemophilia A and 31 (30.1 %) with hemophilia B. Among these, five individuals were classified as patients with inhibitors (four with hemophilia A and one with hemophilia B). From the cohort of hemophilia A patients, 36 individuals (35.0 %) were identified as having severe disease; 20 (19.4 %) moderate; and 16 (15.5 %) mild. In the cohort of hemophilia B patients, 14 (13.6 %) were identified as having severe disease; 14 (13.6 %) moderate; and three (2.9 %) mild. The total mean aggregate cost per year (including clotting factor and hospital utilization) for patients with severe hemophilia B was €112,469, compared with €793 for mild hemophilia A. Clotting factor concentrate amounted for 90 % of total cost in severe cases and hospital utilization was also higher in these cases. CONCLUSIONS: Hemophilia treatment is expensive, particularly for patients with severe disease and especially if they develop inhibitors to replacement clotting factors. In our study, severe hemophilia is associated with greater annual total costs in both types of hemophilia (A = €77,587 and B = € 112,469). Patients with inhibitors have costs 3.3 times higher than patients without inhibitors. Age was not associated with significantly greater total costs (clotting factor and hospital visits/hospitalizations).

Hemophilia in the managed care setting.

Hemophilia A and B are chronic inherited bleeding disorders that together rank as one of the most expensive chronic diseases in the United States. Factor replacement products, which are the mainstay of treatment, are among the most expensive therapies, with a total annual cost of more than $250,000 per adult patient in the United States. Indirect costs also contribute to the economic burden and include lost productivity, caregivers' unpaid costs, and hemophiliarelated disability. Advances in hemophilia care have resulted in longer survival and a growing patient population, greater complexity in management of the disorder, and rising treatment costs. The establishment of federally recognized Hemophilia Treatment Centers has decreased costs and improved patient outcomes and quality of life by promoting outpatient, preventive, and homebased care. Successful collaboration among providers and managed care programs can improve outcomes and decrease costs for the delivery of hemophilia services.

Survey of coagulation factor concentrates tender and procurement procedures in 38 European Countries.

INTRODUCTION: Procurement of coagulation factor concentrates (CFCs) for the treatment of haemophilia is a vital process that determines the quantity and quality of factor replacement therapy. AIM: The aim of this study was to examine the different tender and procurement systems used in Europe for the procurement of CFCs and the outcomes produced by the various systems. METHODS: The survey questionnaire consisted of 30 items and explored various aspects of the procurement process including the prices of CFCs. In 2014, the survey was sent out by the European Haemophilia Consortium (EHC) to 45 national haemophilia patient organizations affiliated to the EHC in all European countries as well as to a designated clinician familiar with the procurement process. RESULTS: The survey was completed by 38 European countries. Nineteen countries use a tender process, 17 an alternative procurement process and 2 use a combination of methods. A wide variety of agencies and individuals are involved in the process. Factors associated with optimum outcome and lower prices include a tender process with a specific legal framework and a tender board including haemophilia clinicians and patient organization representatives. Safety was reported as the most important selection criterion but given the safety profile of almost all currently licensed products, price was the main criterion used in many countries. CONCLUSION: The involvement of both clinicians and patient organizations greatly improves the outcome of a tender or procurement process, as does the presence of a legal framework that governs the process.

EQOFIX: a combined economic and quality-of-life study of hemophilia B treatments in France.

BACKGROUND: EQOFIX is a medicoeconomic study that analyzed the health-related quality of life (HRQoL) and costs of care of the moderate and severe forms of hemophilia B, treated on demand or by prophylaxis with either plasma-derived Factor IX (pdFIX) or recombinant FIX (rFIX). STUDY DESIGN AND METHODS: The primary objectives were evaluations of the impact of hemophilia B on HRQoL and of the costs associated with its management. The secondary objectives were evaluations of the clinical efficacy and costs of care of pdFIX and rFIX. In this observational study we included and followed for 1 year severe and moderate hemophilia B patients without inhibitor. HRQoL was evaluated through generic and disease-specific questionnaires. Information on the health resources consumed was collected every 3 months. RESULTS: The EQOFIX cohort was composed of 155 patients, including 51 children and 104 adults, with 114 having severe disease and 41 having moderate disease. The regimens were prophylactic for 61 and on demand for 94. Altogether, 78 were treated with rFIX and 77 with pdFIX. There was no difference in the QoL between the pdFIX and rFIX treatments. The extra cost of prophylaxis was €22,605 per bleeding event prevented. The consumption of FIX was 1.4-fold higher for the patients treated with rFIX than for the patients treated with pdFIX. CONCLUSION: Our findings in a cohort composed of 25% of the French population of moderate and severe hemophilia B patients show, with similar clinical and HRQoL results, that treatment with rFIX is more expensive than treatment with pdFIX.