Background and Importance New strategies have been developed for the prophylactic treatment of patients with haemophilia B (HB) such as extended half-life recombinant factor IX concentrates (rFIX EHL). These products have shown favourable pharmacokinetic properties, attaining a half-life 3- to 5-fold longer in rFIX EHL compared to standard FIX concentrates
Aim and Objectives Efficiency of a pharmacokinetic-based tailored prophylaxis-dosing schedule versus standard dosing (DS) is compared, in HB, treated with two rFIX-EHL.
Material and Methods Observational, analytical, prospective, multicentre study, involving HB patients, being treated with rFIX-EHL linked to albumin (rFIX-FP) or to fragment crystallisable (rFIX-Fc). Demographic and clinical data, and DS and dosing interval (DI) and actual FIX trough levels were recorded. Pharmacokinetic characterisation was performed following both a population (WAPPS-HEMO) and a linear one-compartment (OC) approach. For each approach and rFIX preparation, an estimation of the time to the target trough (5 IU FIX/dL) was made. Statistical analysis was performed by means of the Student-Fisher t-test.
Results Fifteen patients were included, nine being treated with rFIX-FP (mean age, 33 years; weight 60 kg), and six with rFIX-Fc (49 years, 86 kg). Mean DS was 3222 UI (SD, 1716) every 11,9 days (SD, 4,4) for rFIX-FP patients; and 4333 UI (SD, 606) every 14,0 days (SD, 0,0) for rFIX-Fc patients. The individual tailored DI, for a 0,05 UI/dL trough target was: applying OC; 13,6 days (SD, 5,1), -1,8 days (SD, 5,9) vs DS, representing 240 IU/day (SD, 136,1) for rFIX-FP (p=0,40), and 8,6 days (SD, 1,2), +5,4 days (SD, 1,2) vs DS, representing 508 IU/day (SD, 65,6), for rFIX-Fc, (p<0,001). Applying WAPPS-HEMO; it was 15,0 days (SD, 5,1), -3,1 days (SD, 5,3) vs DS, 217 IU/day (SD, 114,7), for rFIX-FP (p=0,12), and 10,2 days (SD, 2,5), +3,8 days (SD, 2,5) vs DS, 449,7 UI/day (SD, 129,1), for rFIX-Fc, (p=0,012).
Conclusion and Relevance Efficiency of rFIX-EHL treatment following a pharmacokinetic-based tailored prophylaxis-dosing schedule versus DS in HB patients, is significantly better. Depending on the commercial preparation, rFIX-FP or rFIX-Fc. Daily-adjusted dose, for a 5 IU FIX/dL trough target, ranges between 217-240 IU/day for rFIX-FP, or 449-508 IU/day for rFIXFc, according to the two pharmacokinetic approaches (OC and population based).
Conflict of Interest No conflict of interest.
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