Pharmacokinetic and clinical improvements after PK-guided switch from standard half-life to extended half-life factor VIII products

Abstract

IntroductionExtended half-life (EHL) factor VIII (FVIII) products have been designed to allow less frequent infusions and higher bleeding protection than standard half-life (SHL) products. Only few reports analyzed this switch in clinical practice.AimTo analyze the differences observed in pharmacokinetics (PK) and clinical outcomes after the switch from SHL to EHL products in severe/moderate haemophilia A (HA) prophylaxis. Materials and methodsObservational, cross-sectional, multicenter, prospective study comparing PK parameters and clinical variables between SHL FVIII replacement therapy followed by EHL along two consecutive one-year periods. PK estimations were performed through WAPPS-Hemo. FVIII consumption, annual bleeding rate (ABR) and annual joint bleeding rate (AJBR) of each period were compared between both periods. ResultsSeventy-five patients were included (median age 26.0 years). After the switch median reductions of 33.3 % in weekly infusion frequency and 20.4 % in dose/kg/week were observed, avoiding 39.1 infusions/patient/year. Significant improvements were achieved in all PK parameters with EHL, showing mean ratios in half-life and area under the curve (AUC) of 1.5 and 1.9. Significant decreases in median ABR (2.0 vs. 0.0), AJBR (1.0 vs. 0.0) and target joints, and zero total bleeds (27.4 % vs. 54.8 %) and zero joint bleeds (42.5 % vs. 72.6 %) were increased after the switch to EHL. Similar improvements were reported in patients <12 and ≥12 years. No differences were observed in PK parameters between EHL products, but lower AJBR were associated to PEGylated products. ConclusionsPK-guided switch to EHL FVIII provided significant improvements in PK and lower bleeding rates, treatment burden and consumption compared to SHL products.