Bayesian pharmacokinetic-guided prophylaxis with recombinant factor VIII in severe or moderate haemophilia A. Issue 174 (February 2019)

• Record Type: Journal Article
• Authors: Megías-Vericat, J.E.; Bonanad, S.; Haya, S.; Cid, A.R.; Marqués, M.R.; Monte, E.; Pérez-Alenda, S.; Bosch, P.; Querol, F.; Poveda, J.L.
• Is Part Of: Thrombosis research. Issue 174(2019)
• Page Start: 151
• Page End: 162
• Publication Date: 2019-02
• Subjects: Pharmacokinetics -- PK-guided prophylaxis -- Bayesian estimation -- myPKFiT -- Recombinant factor VIII -- Haemophilia A; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2018.12.027
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Introduction: Personalised pharmacokinetics (PK) using Bayesian analysis with limited sampling is assumed to help to optimise prophylaxis in haemophilia A (HA) patients. Materials and methods: Our prospective, observational study analysed the influence of PK parameters on clinical variables (bleeding rates, joint status, adherence, and consumption) using myPKFiT® in a cohort of twenty-one severe and moderate HA patients on prophylaxis with recombinant FVIII (Advate®) in two periods of one year, the first before PK-based tailoring and the second after PK-guided prophylaxis. Intra-individual and inter-individual coefficients of variation (CV) of half-life (t1/2 ) were calculated. Results: A total of 73 PK estimations were performed in both periods, resulting in 17.2% inter-individual CV in mean t1/2, and 4.9% intra-individual CV. Before PK-based tailoring a significant association between joint bleeds and t1/2 was found (P = 0.010), especially in patients with short t1/2 . This finding was reproduced (P = 0.013) after withdrawal of two patients with bleeding phenotype related to their advanced arthropathy but normal t1/2 and trough levels. Patients with joint bleeds weighed less (P = 0.039) and required higher doses (P = 0.032) than patients with zero joint bleeds. These associations were not observed in the second period after the adoption of PK-guided prophylaxis. There were no differences between the two periods, although a tendency to fewer spontaneous bleeds was suggested after PK-based tailoring. Conclusions: PK-guided prophylaxis facilitates an adequate level of bleeding control in patients with HA, maintaining clinical variables and patient convenience in an integrative manner, without increasing FVIII consumption. Highlights: A significant association between joint bleeds and short t1/2 was found in patients on standard prophylaxis. A large inter-individual PK variability was found. After PK-guided prophylaxis was established, associations between joint bleeds and t1/2 disappeared. A trend to fewer spontaneous bleeds and lower rFVIII consumption was reported with PK-guided prophylaxis.