Pharmacokinetic strategies for achieving precise factor VIII control with susoctocog alfa in acquired hemophilia A.

Abstract

Background: Recombinant porcine factor (F)VIII (rpFVIII, susoctocog alfa) is used to treat bleeding in patients with acquired hemophilia A (AHA), yet pharmacokinetic (PK) parameters and dosing needs vary widely.

Objectives: To explore the precision of PK-guided bolus dosing and continuous infusion of rpFVIII in AHA.

Methods: We enrolled all AHA patients considered for rpFVIII treatment from 2016 to 2023 at our institution. A user-friendly calculation tool was used to estimate noncompartmental PK parameters from 2 measurements after the initial bolus of rpFVIII, projecting FVIII activity levels for different dosing regimens. PK information was used to guide bolus dosing and continuous infusion, and resulting peak and trough levels were recorded during treatment.

Results: Out of 22 patients enrolled, 21 received rpFVIII for severe bleeding. After the initial bolus, the median incremental recovery was 1.33 U/dL per U/kg (IQR, 0.73-1.90), with a half-life of 3.8 hours (IQR, 1.9-7.6) and clearance of 0.10 dL/h/kg (IQR, 0.06-0.47). Subsequent PK-guided treatment included bolus dosing (n = 9) or continuous infusion (n = 12), both were clinically effective. Continuous infusion provided stable FVIII levels over time in most patients. PK parameters remained consistent, with a slight increase in half-life over the first 10 days.

Conclusion: PK estimates from limited sampling effectively guided rpFVIII bolus and continuous infusion dosing. Continuous infusion provided steady FVIII levels and may offer a practical alternative to bolus dosing.