INTRODUCTION: Inhibitor development to FVIII hemophilia therapy results in increased complications and substantial economic costs. The SIPPET study found higher inhibitor rates in previously untreated patients (PUPs) treated with certain recombinant FVIII (rFVIII) than in PUPs treated with plasma-derived FVIII with Von Willebrand factor (pdFVIII/VWF). The purpose to this study was to quantify differences in FVIII and bypassing agent utilization and to quantify the economic impact of treating PUPs with pdFVIII/VWF vs rFVIII.

METHODS: An Excel-based clinical and economic model using SIPPET study data was developed from a United States healthcare payer perspective over a 5-year treatment period. For the model, it was assumed that 80% of PUPs were treated with FVIII prophylaxis and 20% received on-demand FVIII. FVIII-treated prophylaxis patients received 3 infusions of 40 IU/kg/week and were assumed to have no bleeds. Patients treated with on-demand FVIII had an annualized bleed rate (ABR) of 18.0 bleeds, 10% of which were serious bleeds (ie, requiring hospitalization). Serious bleeds were treated with an average of 1.5 infusions of 50 IU/kg, while minor/moderate bleeds were treated with 1.0 infusion of 25 IU/kg. Inhibitor development rates from the SIPPET study resulted in 18.6% of pdFVIII/VWF patients and 28.4% of rFVIII patients developing high-titer inhibitors. The model also assumed that patients developed their inhibitors over a period of 6 months after treatment initiation (ie, 50 exposure-days) and that those who developed high-titer inhibitors initiated immune tolerance induction (ITI) 3 months after the inhibitor diagnosis. Patients with high-titer inhibitors received bypassing agents (rFVIIa or aPCC) either prophylactically to prevent bleeds or on-demand to treat bleeds. It was assumed that prior to initiating ITI, 50% of patients received prophylaxis; during ITI, all patients received prophylaxis; and after unsuccessful treatment with ITI, all patients received bypassing agents prophylactically. Inhibitor patients successfully treated with ITI returned to FVIII treatment and were assumed to receive FVIII prophylaxis consisting of 3 infusions of 40 IU/kg per week. All cost inputs were identical between the 2 arms, except for the costs of the 2 antihemophilic agents. Treatment costs were calculated monthly using wholesale acquisition cost for medications and were based on patient weight, with total costs being summed over 5 years.

RESULTS: Initiating treatment with pdFVIII/VWF instead of rFVIII in severe hemophilia A PUPs significantly reduced the treatment costs of FVIII replacement, with total FVIII costs of $596,700 and $868,420 respectively. The use of bypassing agents was 35% lower in the pdFVIII than the rFVIII cohort, with costs of $212,947 vs $325,146, respectively. Hospital costs, exclusive of antihemophilic agents, were $19,173 in the pdFVIII/VWF cohort and $17,364 in the rFVIII cohort. Total cumulative costs per patient over the 5-year period were $828,821 for pdFVIII/VWF patients and $1,210,929 for rFVIII patients, representing a total savings of $382,108 per patient over the 5-year period for an average annual savings of $76,422 per patient. This amounted to greater than 30% savings.

CONCLUSION: Treatment of hemophilia A PUPs with pdFVIII/VWF over a 5-year period may lead to lower FVIII and bypassing agent utilization than patients treated with rFVIII, ultimately resulting in significant cost-savings for pdFVIII/VWF-treated patients when compared to rFVIII-treated patients. Further research is warranted to corroborate these findings in real-world analyses.


Sidonio: Shire: Consultancy, Research Funding; Bioverativ: Research Funding; Grifols: Research Funding; CSL Behring: Consultancy; Bioverativ: Consultancy; Novo Nordisk: Consultancy; Bayer: Consultancy. Runken: Grifols: Employment. O'Day: Xcenda: Consultancy, Other: Employed by Xcenda a consulting company that received financial support to conduct the analysis on behalf of Grifols.. Meyer: Xcenda: Consultancy, Other: Employed by Xcenda a consulting company that received financial support to conduct the analysis on behalf of Grifols.. Spears: Grifols: Employment.

Author notes


Asterisk with author names denotes non-ASH members.