Economic evaluation of major knee surgery with recombinant activated factor VII in hemophilia patients with high titer inhibitors and advanced knee arthropathy: exploratory results via literature-based modeling (original) (raw)
Related papers
Health economics of treating haemophilia A with inhibitors
Haemophilia, 2005
Haemophilia is a rare, inherited blood disorder in which blood clotting is impaired such that patients suffer from excessive internal and external bleeding. At present there is no cure for haemophilia A and patients require expensive, lifelong treatment involving clotting factor replacement therapy. Treatment costs are perceived to be higher for patients who have developed inhibitory antibodies to factor VIII, the standard therapy for haemophilia A. However, initial cost analyses suggest that clotting factor therapy with alternative haemostatic agents, such as recombinant activated factor VII or activated prothrombin complex concentrate, is no more expensive for the majority of haemophilia A patients with inhibitors than for those without inhibitors. With the availability of effective alternative haemostatic agents, orthopaedic surgery for haemophilia A patients with inhibitors is now a clinical option, and initial cost analyses suggest this may be a cost-effective treatment strategy for patients with inhibitors whose quality of life (QoL) is severely impaired by joint arthropathy. In an era of finite healthcare resourcing it is important to determine whether new treatments justify higher unit costs compared with standard therapies and whether such higher costs are justified from an individual perspective in terms of improved QoL, and from a societal perspective in terms of improved productivity and reduced overall healthcare costs. This paper examines current data on the health economics of treating haemophilia A patients with inhibitors, focusing on the overall costs of clotting factor replacement therapy and the cost consequences of joint replacement.
Journal of managed care & specialty pharmacy, 2016
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. To estimate aPCC and rFVIIa prophylaxis costs relative to rFVIIa on-demand treatment cost based on rFVIIa doses reported in U.S. registries. A literatu...
Journal of Medical Economics, 2021
A c c e p t e d M a n u s c r i p t Adult lifetime cost of hemophilia B management in the US: Payer and societal perspectives from a decision analytic model Aims: Hemophilia B (HB) is a rare congenital disorder characterized by bleedingrelated complications which are managed by prophylactic or post-bleeding event ("ondemand") replacement of clotting factor IX (FIX). The standard of care for severe HB is lifelong prophylaxis with standard half-life (SHL) or extended half-life (EHL) products given every 2-3 or 7-14 days, respectively. FIX treatment costs in the US have been investigated, but the lifetime costs of HB treatment have not been well characterized, particularly related to the impact of joint health deterioration and associated health resource utilization. We developed a decision-analytic model to explore outcomes, costs and underlying cost drivers associated with FIX treatment options over the lifetime of an adult with severe or moderately severe HB. Materials and Methods: With participation from clinicians, health technology assessment specialists and patient advocates, a Markov model was constructed to estimate bleeding events and costs associated with health states including 'bleed into joint', 'bleed not into joint', 'no bleed' and death. Sub-models of joint health were based on 0, 1, or ≥2 areas of chronic joint damage. US third-party payer and societal perspectives were considered with a lifetime horizon; sensitivity analyses tested the robustness of primary findings.
Haemophilia, 2015
To investigate the safety, cost-effectiveness, and clinical outcomes of simultaneous bilateral total knee arthroplasty (TKA) in hemophilic arthropathy (HA), the requirements for transfusions, complications, costs, hospital stays, Hospital for Special Surgery (HSS) knee scores, knee range of motion (ROM) and revision rates were compared between simultaneous bilateral and unilateral TKA in HA patients. A total of 36 patients and 54 knees were included. Compared to the unilateral group, the bilateral group did not require more transfusions (2.39 ± 3.13 vs 0.83 ± 1.38 units of RBCs, p > 0.05) or consumption of coagulation factors (50091.67 ± 25168.5 vs 46477.78 ± 11348.32 IU, p > 0.05), complications rate (13/36 vs 6/18, p > 0.05), hospital stay (32.39 ± 19.77 vs 29.11 ± 12.67 days, p > 0.05), or costs excluding prostheses (14945.41 ± 6634.35 vs 14742.12 ± 5746.78 US dollars, p > 0.05). Additionally, the two groups exhibited similar medium-term knee HSS scores (83.67 ± 7.11 vs 81.00 ± 10.35, p > 0.05) and ROM (89.39° ± 13.66° vs 88.91° ± 12.90°, p > 0.05). Our data indicate that bilateral TKA is a safe and cost-effective treatment for HA with similar medium-term results compared to unilateral TKA. Hemophilic arthropathy (HA) is a common and occasionally inevitable complication that affects greater than 90% of patients with hemophilia before the age of 30 1. Multiple joints, including the knee and hip, are often involved, leading to loss of function and permanent disabilities in end stage 2-5 (Fig. 1). The pathogenesis of HA begins with hemophilic synovitis induced by recurrent hemarthrosis, followed by joint erosion with cartilage damage and erosion of adjacent bones 6. The most important approach to prevent HA involves eliminating intra-articular hemorrhage by regular factor replacement therapy (FRT) 7. However, 70-80% of patients with hemophilia can not receive appropriate treatment and are thus at increased risk of developing HA 8 , and the knee joint is regarded as one of the most vulnerable joints 9. Total knee arthroplasty (TKA) has been considered an optimal choice for treatment of HA 10-16 , and FRT is imperative in maintaining an adequate level of clotting factors to minimize blood loss perioperatively 8,17,18. Given that HA of both knees is often involved, bilateral TKA is always unavoidable in the end stage. As staged bilateral TKA requires repeated clotting factor infusions that may induce the development of inhibitory against coagulation factors 19,20 as well as increases in hospitalization costs, simultaneous bilateral TKA may be considered a better treatment option. We conducted this retrospective study of 36 patients with a mean follow-up of 6 years to investigate the safety, cost-effectiveness, and medium-and long-term clinical outcomes of patients with end-stage HA receiving simultaneous bilateral TKA compared to unilateral TKA. We propose a hypothesis that the clinical results of simultaneous bilateral TKA were not inferior to unilateral TKA in HA patients. Methods Study design. We searched the database of a single center for patients older than 18 years with end-stage HA (Fig. 2) who were treated with TKA from April 2005 to April 2015. The inclusion criteria were as follows: a) patients with hemophilia who had incapacitating HA; b) only TKA was performed during one admission.
Haemophilia, 2008
Arthropathy is prevalent in patients with haemophilia and inhibitors and is a major source of pain and disability, significantly reducing quality of life. Recombinant activated factor VII (rFVIIa; NovoSeven Ò ) is one of the treatments available for acute life-threatening bleeding episodes in haemophilia patients with inhibitors. It has also been used successfully in a range of orthopaedic surgical procedures in these patients. This is a review of published data on elective orthopaedic procedures in haemophilia patients with inhibitors under cover of rFVIIa from January 2002 to November 2006. Articles were retrieved from MEDLINE using specified search parameters. Twelve articles covering a total of 80 orthopaedic procedures were identified. In the vast majority of cases, rFVIIa provided safe and effective haemostatic cover during orthopaedic surgery with no bleeding complications. There was variation in the administered dose, although the majority of patients were treated with 90 lg kg )1 bolus followed by either continuous infusion or bolus infusion. Of those cases reporting bleeding complications, most were considered to be related to an inadequate amount of rFVIIa. The cumulative experience presented here suggests that rFVIIa is safe and effective for providing adequate haemostatic cover for haemophilia patients with inhibitors undergoing orthopaedic surgery. The optimal dosing regimen and mode of administration has yet to be identified. Further controlled trials are needed to confirm these experiences.
Blood, 2003
Inhibitors in patients with hemophilia are a rare complication of a rare disease causing pain and disability in patients and impairment to the quality of their lives. Recent advances in treatment have brought improvements, but they have done so by absorbing larger amounts of financial resources. This study involved 52 Italian patients with hemophilia with high-responding inhibitors who were longitudinally observed for 18 months to evaluate concomitantly cost of care and quality of life. Overall, 0.6 bleeding episodes per patient per month were recorded. This frequency of events was lower than that reported in other cohorts of patients with hemophilia who were not taking inhibitors. The average monthly cost of care was, in euros, €18 000 (US $18 000) per patient, mainly because of treatment products. Recombinant activated factor VII, mostly used for orthopedic surgery, represented 50% of the expenses. Quality of life, measured through validated questionnaires, was similar to that of ...
ClinicoEconomics and Outcomes Research, 2021
Background: The standard of care for patients with hemophilia A is prophylaxis with factor VIII (FVIII) therapies. Extended half-life (EHL) FVIII products offer a reduced infusion burden compared with standard FVIII treatments. However, comparative evidence between EHLs is lacking. Objective: To develop a pharmacodynamic-pharmacokinetic decision model to predict comparative bleed outcomes of adolescents and adults with hemophilia A receiving treatment with various EHL FVIII therapies, capturing differences in cumulative bleeding episodes, breakthrough bleed resolution and resource costs, as well as quality-adjusted life years (QALYs). Methods: The patient population from the pathfinder 2 Phase III clinical trial was used to understand the link between FVIII levels and annual bleeding rates (ABRs). Pharmacokinetic/pharmacodynamic modeling was subsequently applied to estimate FVIII levels for four EHL FVIII treatments (turoctocog alfa pegol [Esperoct ® ], rurioctocog alfa pegol [Adynovi ® ], efmoroctocog alfa [Elocta ® ], and damoctocog alfa pegol [Jivi ® ]) to predict comparative ABRs. FVIII consumption costs (due to prophylactic treatment and breakthrough bleed resolution) and resource costs, as well as QALYs, were subsequently estimated from a UK NHS perspective over a 70-year time horizon. Results: Turoctocog alfa pegol prophylaxis resulted in 8-19% fewer cumulative bleeding episodes versus comparators in the base case scenario. Assuming parity in annual prophylaxis costs, turoctocog alfa pegol prophylaxis reduced the cost of product and resource use to resolve a breakthrough bleed by 9-25% versus comparators. Prophylaxis with turoctocog alfa pegol was also associated with the most QALYs, representing a discounted QALY gain of 0.35-1.05 compared with the other treatments. Conclusion: Using a pharmacodynamic-pharmacokinetic decision model, turoctocog alfa pegol prophylaxis was associated with fewer cumulative bleeds, as well as lower product and resource costs related to resolving a breakthrough bleed and most QALYs versus comparators.
The Journal of Arthroplasty, 2019
Background: End-stage hemophilic arthropathy is the result of recurrent joint hemarthroses. Although total hip arthroplasty (THA) and total knee arthroplasty (TKA) can reduce severe joint pain and improve functional activity, controversy remains regarding outcomes after THA and TKA among patients with hemophilia. This study evaluated the risk of adverse outcomes of hemophilia patients who underwent THA and TKA. Methods: This retrospective cohort study was conducted using data from the National Health Insurance Research Database. Patients who had hemophilia and underwent THA and TKA between 2000 and 2015 were identified. A total of 121 patients with hemophilia and 194,026 patients without hemophilia were included. Thorough propensity score matching, patients with hemophilia were matched at a 1:4 ratio to patients without hemophilia. Multivariable regression analysis was used to control for confounding variables and compare the risk of post-operative complications and mortality, differences of length of stay and cost of care for the hospital. Results: After propensity score matching and multivariate regression analysis, the adjusted HR of post-operative transfusion for patients with hemophilia was 5.262 (95% CI=3.044-26.565, P<0.001) in THA group and 6.279 (95% CI=3.246-28.903, P<0.001) in TKA group, when compared with the control group. Patients with hemophilia had longer length of hospital stay (THA group: 95% CI, 1.541-2.669, P < .001; TKA group: 95% CI, 1.568-2.786; P < .001) and higher total hospital charges (THA group: 95% CI, 3.518-8.293, P < .001; TKA group: 95% CI, 3.584-8.842; P < .001) compared to patients without hemophilia. Hemophiliacs had a higher yet nonsignificant 1-year infection rate (8.11% vs. 3.38%,