Prophylaxis in factor IX deficiency product and patient variation

Abstract

To determine the dosing needed to maintain a prophylactic level of factor IX (FIX) >/=2%, 15 non-inhibitor severe (</=1% FIX) deficient subjects participated in a double-blind, two-period crossover study to assess the pharmacokinetics of two FIX concentrates, Mononine (pd-FIX), an ultra-high-purity plasma-derived concentrate, and BeneFix (r-FIX), a recombinant product. The median recovery in the pd-FIX group was 1.67 IU dL(-1) per IU kg-1+/-1.07 vs. 0.86 IU dL(-1) per IU kg(-1)+/-0.32 in the r-FIX group (P = 0.0002). The median half-life for pd-FIX was 12.9 +/-1.7 h compared with 13.7 +/- 2.9 h for r-FIX (P = 0.016). Fitted dose activity curves were computer-simulated to depict multiple-dose activity curves for each patient with each product that would maintain prophylactic levels of >/=2%. Based on pharmacokinetic analysis the median amount of concentrate needed to maintain a prophylactic level >/=2% for 30 days when administered every third day is 677 IU kg(-1) pd-FIX (range 388-6005 IU kg(-1) pd-FIX) compared with 1168 IU kg(-1) r-FIX (range 268-13085 IU kg(-1) r-FIX). The median cost for 30 days of prophylaxis of an average 25-kg 8-year-old child at the current University of Iowa Price (0.87 US dollars Mononine/0.86 US dollars BeneFix as of December 2002) if given every third day would be 19,972 US dollars and 34,456 US dollars for r-FIX. However, because of wide inter-patient variability in recovery and half-life, pharmacokinetic evaluation of each patient is necessary to determine the appropriate dosing schedule and product best suited for prophylaxis.