Clinical benefits of a Bayesian model for plasma-derived factor VIII/VWF after one year of pharmacokinetic-guided prophylaxis in severe/moderate hemophilia A patients.

Abstract Introduction Individual pharmacokinetic (PK) profiling in hemophilia A (HA) helps to individualize prophylaxis using population PK models (popPK). A specific popPK model for plasma-derived factor VIII containing von-Willebrand Factor (pdFVIII/VWF) was developed. Aim To compare standard versus PK-driven prophylaxis, using a generic or a specific popPK model for pdFVIII/VWF. Materials and methods A prospective study conducted in HA patients in prophylaxis with pdFVIII/VWF (Fanhdi®) comparing three one-year study periods: (1) standard prophylaxis, (2) PK-guided prophylaxis using a generic pdFVIII popPK model which described FVIII activity irrespective of FVIII concentrate, and (3) PK-guided prophylaxis with specific pdFVIII/VWF popPK model. PK parameters analyzed were half-life, trough levels (TL) at 24, 48 and 72 h, and time to reach FVIII levels of 1, 2, 5% (T5%). Clinical outcomes were dose/kg, FVIII consumption, annualized bleeding rate (ABR), annualized joint bleeding rate (AJBR), spontaneous and traumatic bleeds. Results Of the 30 analyzed patients, 28 had severe HA and the median age was 31.2. Fifteen patient's prophylaxis doses were PK-adjusted. After the generic PK-guided prophylaxis period, younger patients showed more joint bleeds, a shorter half-life, and lower TL48, TL72 and T5%. Using the specific pdFVIII/VWF popPK model compared with standard prophylaxis, a lower spontaneous AJBR was observed in the entire cohort and in patients aged >15 years. Additionally, lower spontaneous ABR was reported in patients aged ≤15 years comparing specific and generic models. Conclusions PK-guided prophylaxis with a specific pdFVIII/VWF popPK model allowed treatment individualization and improved bleeding control in routine clinical practice, especially in younger patients with short pdFVIII/VWF half-lives.