Prophylaxis in factor IX deficiency product and patient variation

Summary.  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 Mononine/$0.86 BeneFix as of December 2002) if given every third day would be $19 972 and $34 456 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.