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.

Health-related quality of life and healthcare costs of symptoms and cardiovascular disease events in patients with atrial fibrillation: a longitudinal analysis of 27 countries from the EURObservational Research Programme on Atrial Fibrillation general long-term registry.

AIMS: We examine the effects of symptoms and cardiovascular disease (CVD) events on health-related quality of life (HRQOL) and healthcare costs in a European population with atrial fibrillation (AF). METHODS AND RESULTS: In the EURObservational Research Programme on AF long-term general registry, AF patients from 250 centres in 27 European countries were enrolled and followed for 2 years. We used fixed effects models to estimate the association of symptoms and CVD events on HRQOL and annual healthcare costs. We found significant decrements in HRQOL in AF patients in whom ST-segment elevation myocardial infarction (STEMI) [-0.075 (95% confidence interval -0.144, -0.006)], angina or non-ST-elevation myocardial infarction (NSTEMI) [-0.037 (-0.071, -0.003)], new-onset/worsening heart failure [-0.064 (-0.088, -0.039)], bleeding events [-0.031 (-0.059, -0.003)], thromboembolic events [-0.071 (-0.115, -0.027)], mild symptoms [0.037 (-0.048, -0.026)], or severe/disabling symptoms [-0.090 (-0.108, -0.072)] occurred during the follow-up. During follow-up, annual healthcare costs were associated with an increase of €11 718 (€8497, €14 939) in patients with STEMI, €5823 (€4757, €6889) in patients with angina/NSTEMI, €3689 (€3219, €4158) in patients with new-onset or worsening heart failure, €3792 (€3315, €4270) in patients with bleeding events, and €3182 (€2483, €3881) in patients with thromboembolic events, compared with AF patients without these events. Healthcare costs were primarily driven by inpatient costs. There were no significant differences in HRQOL or healthcare resource use between EU regions or by sex. CONCLUSION: Symptoms and CVD events are associated with a high burden on AF patients and healthcare systems throughout Europe.

Contemporary clinical and economic outcomes among oral anticoagulant treated and untreated elderly patients with atrial fibrillation: Insights from the United States Medicare database.

BACKGROUND: Oral anticoagulants (OACs) mitigate the risk of stroke in atrial fibrillation (AF) patients. OBJECTIVE: Elderly AF patients who were treated with OACs (apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin) were compared against AF patients who were not treated with OACs with respect to their clinical and economic outcomes. METHODS: Newly diagnosed AF patients were identified between January 2013 and December 2017 in the Medicare database. Evidence of an OAC treatment claim on or after the first AF diagnosis was used to classify patients into treatment-defined cohorts, and these cohorts were further stratified based on the initial OAC prescribed. The risks of stroke/systemic embolism (SE), major bleeding (MB), and death were analyzed using inverse probability treatment weighted time-dependent Cox regression models, and costs were compared with marginal structural models. RESULTS: The two treatment groups were composed of 1,421,187 AF patients: OAC treated (N = 583,350, 41.0% [36.4% apixaban, 4.9% dabigatran, 0.1% edoxaban, 26.7% rivaroxaban, and 31.9% warfarin patients]) and untreated (N = 837,837, 59.0%). OAC-treated patients had a lower adjusted risk of stroke/SE compared to untreated patients (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.68-0.72). Additionally patients receiving OACs had a lower adjusted risk of death (HR: 0.56; 95% CI: 0.55-0.56) and a higher risk of MB (HR: 1.57; 95% CI: 1.54-1.59) and this trend was consistent across each OAC sub-group. The OAC-treated cohort had lower adjusted total healthcare costs per patient per month ($4,381 vs $7,172; p < .0001). CONCLUSION: For the OAC-treated cohort in this elderly US population, stroke/SE and all-cause death were lower, while risk of MB was higher. Among OAC treated patients, total healthcare costs were lower than those of the untreated cohort.

Characterization and treatment of immune thrombocytopenia in Europe: a qualitative observational study.

BACKGROUND: Immune thrombocytopenia (ITP) is a rare disease, characterized by increased platelet destruction/suboptimal platelet production, leading to thrombocytopenia and risk of severe bleeding events. METHODS: Interviews with 23 physicians and 12 payors, a survey with 113 physicians and validation using published data were used to define the current treatment paradigm and healthcare resource utilization and to determine the costs associated with managing acute bleeds in six European countries (Germany, Spain, France, Italy, Netherlands, UK). The study estimated a prevalence of 9 to 10 per 100,000 adults in 2020 across all six countries (disease severity split: 34% mild, 32% moderate, 33% severe (due to rounding up some values might not sum up to 100%). RESULTS: Physician feedback showed that most patients with ITP (60%) received first-line treatment or were monitored by their physician; ∼75% of patients relapsed within 3-4 months. Thrombopoietin-receptor agonists (TPO-RAs) and rituximab were used to achieve disease stabilization in patients who relapse; patients could switch to an alternative TPO-RA to control symptoms, manage side-effects or improve adherence. The costs of rescue therapies and hospital services (e.g. surgery and admissions) accounted for the majority of healthcare resources to manage bleeding events. CONCLUSION: Physicians would welcome earlier use of TPO-RAs to help maintain long-term control of ITP bleeds and potentially reduce both hospitalization and therapy costs.

Clinical and Economic Outcomes Among Nonvalvular Atrial Fibrillation Patients With Coronary Artery Disease and/or Peripheral Artery Disease.

To address literature gaps on treatment with real-world evidence, this study compared effectiveness, safety, and cost outcomes in NVAF patients with coronary or peripheral artery disease (CAD, PAD) prescribed apixaban versus other oral anticoagulants. NVAF patients aged ≥65 years co-diagnosed with CAD/PAD initiating warfarin, apixaban, dabigatran, or rivaroxaban were selected from the US Medicare population (January 1, 2013 to September 30, 2015). Propensity score matching was used to match apixaban versus warfarin, dabigatran, and rivaroxaban cohorts. Cox models were used to evaluate the risk of stroke/systemic embolism (SE), major bleeding (MB), all-cause mortality, and a composite of stroke/myocardial infarction/all-cause mortality. Generalized linear and two-part models were used to compare stroke/SE, MB, and all-cause costs between cohorts. A total of 33,269 warfarin-apixaban, 9,335 dabigatran-apixaban, and 33,633 rivaroxaban-apixaban pairs were identified after matching. Compared with apixaban, stroke/SE risk was higher in warfarin (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.61 to 2.31), dabigatran (HR: 1.69; 95% CI: 1.18 to 2.43), and rivaroxaban (HR: 1.24; 95% CI: 1.01 to 1.51) patients. MB risk was higher in warfarin (HR: 1.67; 95% CI: 1.52 to 1.83), dabigatran (HR: 1.37; 95% CI: 1.13 to 1.68), and rivaroxaban (HR: 1.87; 95% CI: 1.71 to 2.05) patients vs apixaban. Stroke/SE- and MB-related medical costs per-patient per-month were higher in warfarin, dabigatran, and rivaroxaban patients versus apixaban. Total all-cause health care costs were higher in warfarin and rivaroxaban patients compared with apixaban patients. In conclusion, compared with apixaban, patients on dabigatran, rivaroxaban, or warfarin had a higher risk of stroke/SE, MB, and event-related costs.

Economic burden of major bleeding events in commercially insured patients with von Willebrand disease based on claims data from the United States.

BACKGROUND: von Willebrand disease (VWD) can lead to serious, life-threatening bleeding events associated with substantial clinical and economic burden. OBJECTIVE: To estimate the prevalence, health care resource utilization (HCRU), and costs associated with major bleeding events in patients with VWD. METHODS: This was a retrospective analysis of the IBM MarketScan database (2008-2016). Selected patients had ≥ 2 VWD diagnoses, no diagnosis of acquired coagulation factor deficiency, and continuous health care plan enrollment for ≥ 12 months from eligibility start date. Prevalence was calculated as the proportion of eligible patients with ≥ 1 major bleeding event during the observation period (start to end of continuous eligibility). HCRU and costs in the 12-month continuous enrollment period following the first major bleeding event were compared with those from a comparable 12-month period for patients without major bleeding events. RESULTS: Of the 19,785 patients with VWD, 15% experienced ≥ 1 major bleeding event during a median follow-up of 4 years; 89% of these events were gastrointestinal bleeds. For the economic analysis, 773 patients with ≥ 1 major bleeding event and 4,285 patients without major bleeding events met the selection criteria. Controlling for baseline covariates, patients with major bleeding events had significantly (P < 0.0001) more inpatient admissions (incidence rate ratio [IRR] = 3.2; 95% CI = 2.78-3.77), longer inpatient stays (IRR = 3.9; 95% CI = 3.12-4.93), and more emergency department visits (IRR = 2.0; 95% CI = 1.77-2.27) and outpatient visits (IRR = 1.3; 95% CI = 1.19-1.34) than patients without major bleeding events. Annual health care costs were significantly higher (P < 0.01) for patients with major bleeding events than those without them (predicted mean cost differences: total = $20,890, pharmacy = $2,593, and medical = $18,293). CONCLUSIONS: Major bleeding events were associated with increased HCRU and costs, mostly inpatient costs. Therefore, optimizing therapy to prevent or reduce major bleeding events has the potential to reduce health care use and costs in patients with VWD. DISCLOSURES: This study was funded by Baxalta U.S. Inc., a Takeda company (Lexington, MA). The study sponsor was involved with the study design, analysis, and interpretation of data; writing of the manuscript; and the decision to publish the article. Lu, Wu, and Ewenstein are employees of Baxalta U.S. Inc., a Takeda company, and are Takeda stock owners. Farahbakhshian is an employee of Shire U.S. Inc., a Takeda company, and is a Takeda stock owner. Oladapo was an employee of Baxalta U.S. Inc., a Takeda company, at the time the analysis was completed and the manuscript developed, and is a Takeda stock owner.

Cost effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura.

Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by thrombotic microangiopathy leading to end-organ damage. The standard of care (SOC) treatment is therapeutic plasma exchange (TPE) alongside immunomodulation with steroids, with increasing use of rituximab ± other immunomodulatory agents. The addition of caplacizumab, a nanobody targeting von Willebrand factor, was shown to accelerate platelet count recovery and reduce TPE treatments and hospital length of stay in TTP patients treated in 2 major randomized clinical trials. The addition of caplacizumab to SOC also led to increased bleeding from transient reductions in von Willebrand factor and increased relapse rates. Using data from the 2 clinical trials of caplacizumab, we performed the first-ever cost-effectiveness analysis in TTP. Over a 5-year period, the projected incremental cost-effectiveness ratio (ICER) in our Markov model was $1 482 260, significantly above the accepted 2019 US willingness-to-pay threshold of $195 300. One-way sensitivity analyses showed the utility of the well state and the cost of caplacizumab to have the largest effects on ICER, with a reduction in caplacizumab cost demonstrating the single greatest impact on lowering the ICER. In a probabilistic sensitivity analysis, SOC was favored over caplacizumab in 100% of 10 000 iterations. Our data indicate that the addition of caplacizumab to SOC in treatment of acquired TTP is not cost effective because of the high cost of the medication and its failure to improve relapse rates. The potential impact of caplacizumab on health system cost using longer term follow-up data merits further study.

Multi-Criteria Model for Evaluating Drugs to Prevent Deep Venous Thrombosis Associated With Orthopedic Surgery: A Hospital-Based Case Study.

BACKGROUND: It's estimated that 40% to 60% of patients undergoing major orthopedic surgery of the hip or knee who do not receive thromboprophylaxis will develop deep venous thrombosis Instituto Nacional de Traumatologia e Ortopedia has established a guideline to prevent DVT with the administration of the Enoxaparin. Recently, institute stakeholders have been questioning this guideline as new oral anticoagulants that offer more comfort and efficacy, but present higher risk of bleeding, have been appearing in the market for treating deep venous thrombosis. OBJECTIVE: This study aims to validate the application of a multicriteria decision analysis in a real-world problem, the use of rivaroxaban and enoxaparin to prevent deep venous thrombosis. METHODS: The multicriteria method MACBETH (Measuring Attractiveness by a Categorical Based Evaluation Technique) was used in a decision conferencing process to develop an evaluation model for measuring the relative value of the drugs on each evaluation criterion, separately and globally. The model-building process was informed by a literature review and meta-analysis of randomized clinical trials with a critical appraisal of the evidence. RESULTS: We report a model-structure with eight criteria, each one associated with a weighting coefficient and value function. Following a simple additive aggregation process, the model-outputs showed that Rivaroxaban was considered a robust option for DVT. Sensitivity analysis and robustness analysis were performed and testify the consistency of the results. CONCLUSION: This article contributes to literature by showing how MACBETH method can be combined with scientific evidence and participatory group processes, for health technology assessment in hospitals.

The strengths and weaknesses of viscoelastic testing compared to traditional coagulation testing.

Optimized acute bleeding management requires timely and reliable laboratory testing to detect and diagnose coagulopathies and guide transfusion therapy. Conventional coagulation tests (CCT) are inexpensive with minimal labor requirements, but CCTs may have delayed turnaround times. In addition, abnormal CCT values may not reflect in vivo coagulopathies that require treatment and may lead to overtransfusion. The use of viscoelastic testing (VET) has been rapidly expanding and is recommended by several recent bleeding guidelines. This review is intended to compare CCT to VET, review the strengths and weaknesses of both approaches, and evaluate and summarize the clinical studies that compared CCT-based and VET-based transfusion algorithms. Most studies of CCT vs VET transfusion algorithms favor the use of VET in the management of massively bleeding patients due to reductions in blood product utilization, bleeding, costs, and lengths of stay.

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.

Add-On Therapies in Cardiovascular Disease: Reviewing ICER's Report and the Potential Effect on Payers.

DISCLOSURES: No outside funding supported this commentary. The authors have nothing to disclose.

The Effectiveness and Value of Rivaroxaban and Icosapent Ethyl as Additive Therapies for Cardiovascular Disease.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM), New England States Consortium Systems Organization, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Health Care, Kaiser Foundation Health Plan, and Partners HealthCare to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Pearson is employed by ICER; Synnott was employed by ICER at the time of this report. Ollendorf, Campbell, and McQueen received grants from ICER for work on this review. Ollendorf also reports advisory board, consulting, and other fees from Sarepta Therapeutics, DBV Technologies, EMD Serono, Gerson Lehman Group, The CEA Registry Sponsors, Autolus, Analysis Group, Amgen, AbbVie, Cytokinetics, Aspen Institute/University of Southern California, and University of Colorado, unrelated to this review.

Comparative Clinical and Economic Outcomes Associated with Warfarin Versus Apixaban in the Treatment of Patients with Venous Thromboembolism in a Large U.S. Commercial Claims Database.

BACKGROUND: Venous thromboembolism (VTE), constituting deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common cause of vascular-related morbidity and mortality, resulting in a significant clinical and economic burden in the United States each year. Clinical guidelines recommend that patients with DVT and PE without cancer should be initiated on anticoagulation therapy with a direct oral anticoagulant over a vitamin K antagonist. Yet there is limited real-world evidence comparing the economic burden of warfarin and apixaban in treating VTE patients in a large commercially insured population. OBJECTIVE: To compare safety and effectiveness of warfarin and apixaban and evaluate associated economic burden in treating VTE patients in a large U.S. commercial health care claims database. METHODS: The PharMetrics Plus database was used to identify oral anticoagulant (OAC)-naive patients aged ≥ 18 years who initiated apixaban or warfarin within 30 days of a qualifying VTE encounter and had continuous health plan enrollment with medical and pharmacy benefits for 6 months before treatment initiation. Apixaban initiators and warfarin initiators were matched using the propensity score matching (PSM) technique. Cox proportional hazard models were used to assess and compare the risk of major bleeding (MB), clinically relevant nonmajor (CRNM) bleeding, and recurrent VTE. Generalized linear models were used to assess and compare the all-cause health care costs. A 2-part model with bootstrapping was used to evaluate MB- and recurrent VTE-related medical costs. RESULTS: Among 25,193 prematched patients, 13,421 (53.3%) were prescribed warfarin and 11,772 (46.7%) were prescribed apixaban. After 1:1 PSM, 8,858 matched warfarin-apixaban pairs were selected with a mean follow-up of 109 days and 103 days, respectively. Warfarin was associated with a significantly higher risk of MB (HR = 1.52, 95% CI = 1.14-2.04), CRNM bleeding (HR = 1.27, 95% CI = 1017.15-1.40), and recurrent VTE (HR = 1.50, 95% CI = 1.24-1.82) compared with apixaban. Warfarin patients had significantly higher all-cause medical costs per patient per month (PPPM; $2,333 vs. $1,992; P = 0.001), MB-related costs PPPM ($112 vs. $65; P = 0.020), and recurrent VTE-related costs PPPM ($287 vs. $206; P = 0.014) compared with apixaban patients. Warfarin patients had similar all-cause total health care costs PPPM ($2,630 vs. $2,420; P = 0.051) compared with apixaban patients. CONCLUSIONS: Warfarin use was associated with a higher risk of MB, CRNM bleeding, and recurrent VTE compared with apixaban. Warfarin use was also associated with higher all-cause medical costs, MB-related medical costs, and recurrent VTE-related costs PPPM compared with apixaban. DISCLOSURES: This study was funded by Bristol Myers Squibb and Pfizer, which were also involved in the study design, as well as writing and revising of the manuscript. Guo, Rajpura, Okano, and Rosenblatt are employees of Bristol Myers Squibb. Hlavacek, Mardekian, and Russ are employees of Pfizer. Keshishian, Sah, Delinger, and Mu are employees of SIMR, LLC, which received funding from the study sponsors to conduct this study.

Antithrombotic and hemostatic stewardship: evaluation of clinical outcomes and adverse events of recombinant factor VIIa (Novoseven®) utilization at a large academic medical center.

BACKGROUND: Recombinant factor VIIa (rFVIIa) (Novoseven®) is utilized for the reversal of anticoagulation-associated bleeding and refractory bleeding in cardiac surgery. In August 2015, rFVIIa was transferred from the blood bank to the pharmacy at New York University (NYU) Langone Health. Concordantly, an off-label dosing guideline was developed. The objective of this study was to describe utilization and cost of rFVIIa and assess compliance to our dosing guideline. METHODS: We performed a retrospective, observational review of rFVIIa administrations post-implementation of an off-label dosing guideline. All patients who received rFVIIa between September 2015 and June 2017 were evaluated. For each rFVIIa administration, anticoagulation and laboratory values, indications for use, dosing, ordering and administration times, concomitant blood products, and adverse events were collected. Adverse events included venous thromboembolism, stroke, myocardial infarction, and death due to systemic embolism and mortality. The primary endpoint was the utilization of rFVIIa in accordance with the off-label dosing guideline. Secondary endpoints included hemostatic efficacy of rFVIIa, adverse events, blood products administered, and cost-effectiveness of rFVIIa transition to pharmacy. RESULTS: A total of 63 patients [pediatric (n = 6), adult (n = 57)] received rFVIIa, with the majority of use for refractory bleeding after cardiac surgery. The utilization of rVIIa decreased after development of the off-label dosing guideline and transition from blood bank to pharmacy. The total incidence of thromboembolic events within 30 days was 19.6%; 17.6% arterial and 2% venous; 70% of patients with an adverse event were over 70 years of age. Use of rFVIIa reduced the median number of units of blood products administered. CONCLUSION: Administration of rFVIIa for cardiac surgery appears to be effective for hemostasis. Transitioning rFVIIa from the blood bank to pharmacy and implementation of a dosing guideline appears to have reduced utilization. Patients receiving rFVIIa should be monitored for thromboembolic events. Elderly patients may be at higher risk for thromboembolic events.

Assessing the potential cost-effectiveness of a gene therapy for the treatment of hemophilia A.

Aim: Hemophilia A is a genetic, chronic disorder classified by deficient or defective coagulation factor VIII (FVIII) that puts those affected at risk for spontaneous bleeding episodes, which lead to joint damage and chronic pain over time. Currently, most severe hemophilia A patients are treated with prophylactic FVIII, which requires costly and frequent infusions and life-long adherence to medication. A gene therapy (valoctocogene roxaparvovec) is currently in development for the treatment of severe hemophilia A. This model assessed the potential cost-effectiveness of treating patients with valoctocogene roxaparvovec rather than prophylactic therapy.Materials and methods: We developed an individual-based, state-transition microsimulation model for assessing the likely cost-effectiveness of valoctocogene roxaparvovec compared to prophylactic FVIII. Men aged 30 with severe hemophilia A were modeled over a lifetime horizon, and costs were reported from the perspective of the United States health care system. Through microsimulation, patient-level heterogeneity was captured in starting weight, starting Pettersson score (PS), durability of valoctocogene roxaparvovec, and annual bleed rate (ABR).Results: The model projects that treatment with single-administration valoctocogene roxaparvovec would be cost-saving to people with hemophilia A at a price point comparable to other currently available gene therapy products due to its potential to reduce FVIII utilization, direct medical costs, lifetime bleeds, and accumulated joint damage.Limitations: The model relies upon evidence-based assumptions for clinical inputs due to limited data availability. Such uncertainty was mitigated by modeling heterogeneity across the population, specifically with regards to long-term gene therapy durability, lifetime bleed rates, and joint damage progression.Conclusion: Valoctocogene roxaparvovec was found to be cost-saving-on average by about $6.8 million per patient-and more effective than prophylactic therapy for treatment of hemophilia A. The comparative benefit of gene therapy was observed across a broad range of simulated patients that were representative of the real-world severe hemophilia A population.

An economic analysis of different treatments for bleeding in patients with acquired haemophilia.

BACKGROUND: Acquired haemophilia A (AHA), with potentially high risk of morbidity and mortality, occurs as a result of inhibitors against factor VIII. Bleeding due to AHA can be treated with activated prothrombin complex concentrate (aPCC), recombinant activated factor VII (rFVIIa) or recently, recombinant porcine-sequence factor VIII (rpFVIII). We extended our previous cost-effectiveness analysis (CEA) comparing rpFVIII against the available traditional options. METHODS: For high-titred, haemorrhaging AHA patients treated with either aPCC, rFVIIa or rpFVIII, over the course of 6-days, a Markov simulation was conducted to evaluate the outcomes when these patients transitioned into any of the four following health states: (1) continuous bleeding, (2) thrombosis, (3) stop bleeding and (4) death, with states (2), (3) and (4) modelled as absorbing states. All model parameters were obtained from the medical literature, except the costs of aPCC, rFVIIa and the factor VIII assay, which came from our institutional data. RESULTS: Excluding the cost of the initial treatment on day 0, the total subsequent treatment cost of rFVIIa was substantially more than the costs of aPCC and rpFVIII ($13 925 vs. $1778 vs. $6957, respectively). The average quality-adjusted life days (QALDs) gained from rpFVIII was lowest (4·89 vs. 4·9 for rFVIIa and 4·91 for aPCC). Overall, aPCC dominated the other two treatments. The model was determined to be robust across the tested ranges for all input variables. CONCLUSION: Based on this economic model, for AHA patients with high titres who were bleeding, aPCC was the most cost-effective treatment option and may be considered for use if there is no clinical contraindication.

Societal costs of venous thromboembolism and subsequent major bleeding events: a national register-based study.

AIMS: Detailed evidence on the societal costs of venous thromboembolism (VTE), i.e. deep vein thrombosis (DVT) and pulmonary embolism (PE), and of subsequent major bleeding events, e.g. intracranial and gastrointestinal bleedings, is limited. The objective was to estimate the average 3-year societal event costs attributable to VTE and subsequent major bleedings in Denmark. METHODS AND RESULTS: Based on nationwide Danish registers, each incident patient diagnosed with VTE in the period from 2004 to 2016 was identified and matched with four non-VTE patients by nearest-neighbour propensity score matching. For bleeding patients, the reference cohort was VTE patients without bleedings. Event costs in terms of VTE, DVT, PE, and major bleedings in VTE patients were measured by the 'difference-in-actual-cost' method within 3 years after the incidence. Societal costs included healthcare costs (primary care, hospital, and prescription medicine), municipality home care services, and production loss. The study population included 74 137 VTE incident patients (DVT: 43 099; PE: 31 038), and 4887 VTE patients with a major bleeding within 3 years from VTE diagnosis. The 3-year attributable societal VTE event costs were 40 024 EUR (DVT: 34 509 EUR; PE: 50 083 EUR) with 53% of these costs appearing in the first incident year. Similar results for major bleedings were 51 168 EUR with 46% of these costs appearing in the first incident year. CONCLUSION: The societal costs of VTE and subsequent major bleedings are substantial and ought to be considered. Estimated costs of events may be informative in evaluating the impact of preventive interventions targeting VTE and subsequent major bleedings.

Cost comparison of andexanet versus prothrombin complex concentrates for direct factor Xa inhibitor reversal after hemorrhage.

Andexanet-alpha is a specific reversal agent for direct factor Xa inhibitors (dFXaI). We aimed to project utilization rates and cost of andexanet for reversal of dFXaI-related major hemorrhage compared to 4-factor prothrombin complex concentrates (4F-PCC). A retrospective, multicenter review was conducted between 1/1/2014 and 7/15/2018 of patients who received 4F-PCC for reversal of dFXaI-related life-threatening hemorrhages. Total hospital reimbursements/patient were calculated based on national average MS-DRG payments adjusting for Medicare discounts. The projected cost for andexanet (based on dose and insurance) and % reimbursement/patient was compared to the actual cost of 4F-PCC. Hemostasis at 24 h (excellent/good vs. poor) and 30-day thrombotic complications were assessed. Of 126 patients who received 4F-PCC to reverse dFXaI, 46 (~ 10 per-year) met inclusion criteria. The median projected cost of andexanet was $22,120/patient, compared to $5670/patient for 4F-PCC (P < 0.001). The median hospital reimbursement was $11,492/hospitalization. The projected cost of andexanet alone would exceed the entire hospital reimbursement in 74% of patients by a median of $7604, while 4F-PCC cost exceeded the total hospital payments in 7% of patients in the same cohort (P < 0.001). Hemostasis was excellent/good in 72% of patients post-4F-PCC, compared to 82% in andexanet trials. Thromboembolic events occurred in 4% of patients following 4F-PCC versus 10% in andexanet trials. The projected cost of andexanet would exceed the national average hospital reimbursement/patient in nearly 75% of patients by over $7500/hospitalization. 4F-PCC was significantly less expensive, had lower rates of thrombosis, but also lower rates of good/excellent hemostasis compared to published data for andexanet.