[28]

[28]. and rFVIIIFc prophylaxis. rFVIII product acquisition costs from a published Italian database were included for both prophylaxis and the resolution of breakthrough bleeding. Clinical outcomes within the model were determined based on published annualized bleeding rates and literature regarding the development of target joints (TJs) as the incidence of bleeds and TJs is associated with impaired health-related quality of life. Cost effectiveness was assessed using cost per quality-adjusted life-year (QALY) gained. Results Compared with rFVIII, rFVIIIFc was associated with a per-patient cost saving of approximately 1.3?million and QALY gains of 0.39 over a lifetime horizon. Sensitivity TNFRSF8 analyses considering alternative efficacy, dosing, and structural assumptions each showed that rFVIIIFc dominated rFVIII (i.e., provided more QALYs at a reduced cost). Conclusions This Desacetyl asperulosidic acid cost-effectiveness analysis demonstrated that rFVIIIFc Desacetyl asperulosidic acid may offer a cost-effective treatment option for patients with SHA in Italy. Electronic supplementary material The online version of this article (10.1007/s41669-019-0158-8) contains supplementary material, which is available to authorized users. Key Points for Decision Makers Prophylaxis with recombinant Factor VIII (rFVIII) is the recognized standard of care in severe hemophilia A. However, management with conventional rFVIII therapies requires frequent infusions to maintain trough levels? ?1% to prevent bleeds and joint damage. Factor consumption remains the major contributor to cost in the management of hemophilia.rFVIII Fc fusion protein (rFVIIIFc), with its extended half-life, provides cost savings and improved health-related quality of life compared with conventional rFVIII therapies, based on improved joint health and lower annualized bleed rates. Open in a separate window Introduction Hemophilia A (HA), caused by an inherited deficiency of factor VIII (FVIII), is the most common type of hemophilia, with an incidence of 1 1 in 5000 male births [1]. Patients with HA are at risk of life-threatening bleeding, particularly patients with severe disease (defined as endogenous factor VIII coagulant activity [FVIII:C] level? ?1% of the normal amount), which accounts for approximately 46.2% of Italian cases [2]. More commonly, patients experience bleeding into joints (hemarthroses) and muscles, which can be severely debilitating [3, 4]. Hemarthroses and bleeding into muscles can result in the development of arthropathy (disease of the joint), which is associated with swelling, pain, and reduced movement [4]. Repeated hemarthroses in the same location leads to increased medical resource use and impaired patient health-related quality of life (HRQoL) [5]. As such, the primary treatment goals for patients with severe HA (SHA) pertain to the reduction of bleeding events and the prevention of joint health deterioration. In Italy, the treatment of SHA most commonly involves routine prophylaxis using recombinant FVIII (rFVIII) replacement products as well as episodic rFVIII treatment for the resolution of breakthrough bleeds. Published literature suggests that 90C92% of total direct healthcare costs associated with HA patients are attributable to drug acquisition [6, 7]. Most adult Italian SHA patients are treated with rFVIII prophylaxis, and nearly all pediatric patients are expected to be treated prophylactically [2]. Compared with on-demand use only (i.e., used only for the resolution of a breakthrough bleed), prophylaxis with standard half-life (SHL) rFVIII treatment has been shown to significantly reduce the annualized bleeding rate (ABR) for SHA patients [8C13]. The most commonly used rFVIII product for prophylaxis treatment in Italian practice is Advate? (Shire Pharmaceuticals Ltd) [2, 14]. Extended half-life (EHL) FVIII Fc fusion protein (rFVIIIFc, Elocta?, Swedish Orphan Biovitrum AB) offers an alternative rFVIII treatment option. Its EHL means that patients treated at the same frequency and dose as those using SHL rFVIII products are expected to spend less time below a given targeted trough level (endogenous FVIII:C level) such that the risk of experiencing breakthrough bleeds is reduced [15, 16]. Alternatively, the EHL of rFVIIIFc may permit a reduction in administration frequency versus conventional factor therapies and consequently reduce treatment burden, which may also increase adherence to treatment and improve HRQoL [17]. rFVIIIFc prophylaxis has been studied in both adult and pediatric populations and has been shown to Desacetyl asperulosidic acid be associated with low ABRs as well as improved joint health outcomes (determined via the modified Hemophilia Joint Health Score [mHJHS]) over time [18C20]. Until recently, data regarding the association between joint health and patient HRQoL in patients with SHA were limited. In 2018, OHara et al. [5] published a study.