[Translated article] Pharmacokinetic-guided switching from standard half-life factor VIII to extended half-life pegylated factor VIII in haemophilia A therapy in clinical practice.

Abstract

Objective: To analyse the differences in pharmacokinetic and clinical parameters (bleeding rates and joint health) before and after switching from standard half-life factor VIII (FVIII) to extended half-life pegylated FVIII in patients with severe/moderate haemophilia A on prophylaxis, 1 year before and after the switch in real-life.

Method: This is a single-centre, comparative, observational, sequential, retrospective, and multidisciplinary study. Population pharmacokinetic models from the WAPPS-Hemo® application were used to calculate pharmacokinetic parameters and individualise prophylaxis. The annual rate of total and joint bleeds, joint health (Haemophilia Joint Health Score), plasma half-life and area under the curve ratios, FVIII consumption, administration frequency, and cost were analysed.

Results: Thirty-eight adult patients with haemophilia A who switched from standard half-life FVIII to extended half-life pegylated FVIII were analysed. Significant improvements (P < .05) were observed in all pharmacokinetic parameters, with plasma half-life and area under the curve improvement ratios of 1.5 and 1.9, respectively, as well as reductions in annual total and joint bleeding rates. A higher number of patients with zero total (16.0 vs. 29.0) and joint bleeds (23.0 vs. 33.0) was also observed. The median reductions in administration frequency and dose/kg/week were 30.0% and 19.7%, respectively, avoiding 44.3 infusions/patient/year, resulting in savings of 20,843 €/patient/year. Furthermore, joint health improved (23.0 vs. 21.0; P = .017), and target joints resolved after the switch.

Conclusions: The pharmacokinetically guided switch from standard half-life FVIII to pegylated FVIII demonstrated significant clinical benefits with reduced bleeding rates and improvements in joint health. Additionally, improvements in pharmacokinetic parameters were observed, allowing for reduced treatment burden by decreasing administration frequency, as well as lower consumption and costs.