Improvements in pharmacokinetics, bleeding control, and cost analysis after PK-guided transition to...

Extended half-life factor IX concentrates (FIX-EHL) have been shown to improve clinical outcomes and reduce treatment burden in patients with hemophilia B (HB).

To analyze the differences in pharmacokinetic (PK) and clinical parameters one year before and after the PK-guided switch from standard half-life FIX (FIX-SHL) to FIX-EHL in patients with severe/moderate HB on prophylaxis.

A multicenter, comparative, observational, sequential, retrospective, and multidisciplinary study was conducted. PK parameters were calculated with WAPPS-Hemo®, and annualized total (ABR) and joint bleeding rates, the t_1/2 ratio and area under the curve (AUC), FIX consumption, infusion frequency, and cost were recorded.

A total of 21 patients (9 pediatric and 12 adult) with HB who switched from FIX-SHL to FIX-EHL were analyzed. All PK parameters improved significantly, with median improvement ratios for t_1/2 and AUC of 4.1 (IQR: 3.4-4.8) and 4.2 (IQR: 2.6-5.0), respectively. Regarding clinical outcomes, the difference in ABR reached statistical significance and among the 6 patients with target joints, 5 (83.3 %) achieved resolution after switching. Infusion frequency and weekly dose were reduced by 50.0 % and 56.3 %, respectively, avoiding 52.1 (IQR: 26.1-67.8) injections and 130,357.3 (IQR: 5142.9-203,357.3) IU of FIX per patient per year. However, the switch resulted in an additional cost of € 28,254.9 (IQR: 4432.1- 44,060.8) per patient per year.

The PK-guided switch from FIX-SHL to FIX-EHL was associated with improvements in all PK parameters, and a significant clinical benefit was also demonstrated with the reduction of the bleeding rates. Following the switch, the weekly dose and administration frequency were reduced; however, this did not result in a cost reduction.