Cost-Effectiveness of Long-Term Prophylaxis Versus on-Demand Treatment with Von Willebrand Factor Concentrate in Severe Inherited Von Willebrand Disease

Introduction: von Willebrand Disease (VWD) is the most common inherited bleeding disorder with significant variability in clinical phenotype. Patients with the most severe forms of VWD suffer from frequent bleeding complications including mucosal bleeding, gastrointestinal hemorrhage, hemarthrosis, and muscle hematomas. Long-term prophylaxis with von Willebrand factor (VWF) concentrate has been shown to reduce the frequency of bleeding episodes, but higher costs associated with regular VWF concentrate administration remains a barrier to access.

Methods: We constructed a Markov state transition model to compare the cost-effectiveness of on-demand treatment (ODT) with long-term prophylaxis (PRO) from a United States (US) societal perspective with costs inflated to 2020 US dollars using the Consumer Price Index. Cycle-length was one month with a one-year time horizon and during each cycle, patients could experience either major (hemarthrosis, gastrointestinal bleeding, muscle hematoma), minor (epistaxis, other mucosal bleeding), or no bleeding. Model inputs for event probabilities, costs, and utility were obtained from previously published literature; while there are no specific utility data for these treatment strategies in VWD patients, we assumed they would be similar to published age-specific utilities used in hemophilia analyses and performed sensitivity analyses to assess these assumptions. The base case scenario was modeled on a 70 kg patient with severe VWD receiving plasma-derived VWF concentrate. In the PRO strategy, patients received 60 units/kg every 3 days. ODT patients were only treated for specific bleeding events (minor bleeding: 60 units/kg every 12 hours for 3 days in the outpatient setting; major bleeding: VWF concentrate 60 units/kg every 12 hours for 5 days in the hospital). Microsimulation of 1000 trials was performed using to calculate mean quality-adjusted life-years (QALYs) and costs associated with the two treatment strategies. TreeAge Pro 2017 (TreeAge Software, Williamstown, MA) was used to construct the model and perform analyses.

Results: In the base-case scenario using plasma-derived VWF concentrate, on-demand treatment resulted in a mean cost of US$1,140,586 (± $65,215) generating 0.52 QALYs (±0.01) while the prophylaxis strategy resulted in a mean cost of US$918,329 (± $94,983) generating 0.8 QALYs (±0.04). The microsimulation was repeated to reflect the cost of recombinant VWF concentrate for prophylaxis and a single dose of recombinant factor VIII. Using recombinant VWF, on-demand treatment resulted in a mean cost of US$1,568,005 (± $94206) and generated 0.52 QALYs (±0.01) while the prophylaxis strategy resulted in a mean cost of US$1,343,715 (± $124,974) and generated 0.8 QALYs (±0.04). One-way sensitivity analysis of model inputs showed this result to be robust, as prophylaxis remained the preferred strategy at a willingness to pay (WTP) threshold of US$150,000/QALY for both plasma-derived and recombinant therapies (Figure).

Conclusions: With greater effectiveness and lower total societal health care costs, the prophylaxis strategy dominated the on-demand treatment strategy. While the cost of long-term prophylaxis is primarily due to the high cost of VWF concentrate every 3 days, this strategy results in significantly fewer bleeding episodes per year resulting in more QALYs. Our findings suggest that when compared to on-demand treatment, long-term prophylaxis with VWF concentrate is a cost-effective strategy in patients with severe forms of VWD, which helps to avoid expensive hospitalizations and decreased quality of life due to bleeding episodes and their complications.