Microsimulation to compare activity-related bleed risks between pharmacokinetic-guided rurioctocog alfa pegol prophylaxis and emicizumab

Abstract

ABSTRACT Background Owing to a lack of clinical study data, computational modeling was used to estimate activity-related bleed risk during prophylaxis with either rurioctocog alfa pegol or emicizumab. Research design and methods A pharmacokinetic (PK)-based computational model was used to estimate factor VIII (FVIII) levels for individual patients in the PROPEL study who were treated with PK-guided rurioctocog alfa pegol prophylaxis targeting FVIII trough levels of 1–3% or 8–12%. Emicizumab was assumed to have 20% FVIII equivalency. Six hypothetical patient activity profiles were created using the National Hemophilia Foundation’s physical activity risk ratings scale. For each profile and treatment regimen combination, the total bleed risk over a 2-week period was estimated relative to a patient who was participating in a low-risk activity with 0% FVIII, and the overall relative bleed risks were compared. Results For all evaluated activity profiles, rurioctocog alfa pegol prophylaxis targeting either 1–3% or 8–12% FVIII trough levels was associated with a lower estimated bleed risk compared with emicizumab prophylaxis with assumed 20% FVIII equivalency (P < 0.001). Conclusion Although this model does not reflect actual patient outcomes, it suggests that PK-guided rurioctocog alfa pegol prophylaxis may reduce the bleed risk during physical activities.