Abstract Number: PB0509
Meeting: ISTH 2021 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: The German Antihemophilic factor (recombinant) (rAHF) Hemophilia A (HA) outcome Database (AHEAD) study (DRKS00000556) is a non-interventional prospective multicenter real-world study that assesses long-term effectiveness and safety of rAHF in patients with HA.
Aims: To describe hemostatic effectiveness of rAHF administered as standard prophylaxis (SP) and individualized pharmacokinetic-guided prophylaxis (PKP) in moderate or severe HA.
Methods: The 7th interim analysis describes results from the safety analysis set (SAS) (data cutoff: Jun 30, 2020). Patients were followed over 7 years; 4 years of follow-up are available for SP versus PKP, because day 1 was reset after patients adopted PKP. Key outcomes included annualized bleeding rates (ABRs [all bleeds]), annualized joint bleeding rates (AJBRs), rAHF consumption, factor VIII (FVIII) trough levels, and adverse events (AEs). Ethics committee approval and patients’ informed consent were obtained.
Results: Of 322 patients in SAS (severe HA, n=258; moderate HA, n=64), 250 received prophylaxis (SP and PKP), 67 on-demand treatment, and 5 immune tolerance induction. Median ABRs were lower in patients receiving PKP versus SP over years 1-3. Similar median AJBRs were observed between groups, although the range was wider in patients receiving SP. A higher proportion of patients receiving PKP versus SP had an ABR or AJBR of zero over years 1-3 (Table 1). Mean annualized total dose over years 1-4 was 5260-5437 IU/kg for SP and 4545-5769 IU/kg for PKP. Mean (median [Q1-Q3]) target FVIII troughs for patients with moderate HA at years 1 (n=2) and 2 (n=1) were 2.2 (2.2[1.0-3.4]) and 1.0 (1.0[NA]). For severe HA, mean (median [Q1-Q3]) FVIII troughs for years 1 (n=14) and 2 (n=7) were 4.4 (3.5[2-5]) and 3.4 (3.0[1.5-5.5]). Treatment-related AEs occurred in 31/322 (9.6%) patients; serious treatment-related AEs, 23/322 (7.1%).
| Year 1 | Year 2 | Year 3 | Year 4 | |||||
| Bleeding rates | SP n=246 |
PKP† n=24 |
SP n=229 |
PKP† n=12 |
SP n=211 |
PKP† n=3 |
SP n=190 |
PKP† n=1 |
| Median ABR (Q1-Q3) |
2 (0-6) | 0 (0-2) | 2 (0-4) | 0 (0-0.5) | 1 (0-5) | 0 (0-1) | 1 (0-4) | 3 (3-3) |
| Median AJBR (Q1-Q3) |
0 (0-2) | 0 (0-0.5) | 0 (0-2) | 0 (0-0) | 0 (0-2) | 0 (0-1) | 0 (0-2) | 1 (1-1) |
| % patients with ABR=0 | 36 | 63 | 36 | 75 | 37 | 67 | 48 | 0 |
| % patients with AJBR=0 | 58 | 75 | 59 | 83 | 56 | 67 | 64 | 0 |
| Consumption | SP n=246 |
PKP* n=24 |
SP n=232 |
PKP* n=14 |
SP n=215 |
PKP* n=3 |
SP n=195 |
PKP* n=1 |
| Mean (SD) annualized total dose, IU/kg | 5340 (3254) |
5652 (2841) |
5437 (3250) |
5000 (2004) |
5318 (3224) |
4545 (941) |
5260 (3045) |
5769 (NA) |
| Median (Q1-Q3) annualized total dose, IU/kg | 4737 (3143-6789) |
4986 (3601-7125) |
4805 (3283-6592) |
4827 (3900-5778) |
4727 (3033-6556) |
4111 (3900-5625) |
4692 (3033-6592) |
5769 (NA) |
| *All patients receiving prophylaxis started on SP but could be switched to PKP. †Patients with HA using the FDA-approved mobile app that allows patients to track treatment with rAHF, view estimated factor VIII levels, and share data with healthcare provider. NA, not available; Q, quartile. |
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Bleeding Rates and Consumption of rAHF in Patients Receiving SP Versus PKP*
Conclusions: These real-world data show improved bleeding rates with PKP versus SP with similar rAHF consumption.
To cite this abstract in AMA style:
Klamroth R, Huth-Kühne A, Kurnik K, Escuriola-Ettingshausen C, Regensburger S, Tang L, Norton J, Fernandez A, Oldenburg J. Does Pharmacokinetic-guided Prophylaxis with Antihemophilic Factor (Recombinant) Improve Bleeding Rates over Standard Prophylaxis? Real-world Data from the AHEAD German Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/does-pharmacokinetic-guided-prophylaxis-with-antihemophilic-factor-recombinant-improve-bleeding-rates-over-standard-prophylaxis-real-world-data-from-the-ahead-german-study/. Accessed September 24, 2023.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/does-pharmacokinetic-guided-prophylaxis-with-antihemophilic-factor-recombinant-improve-bleeding-rates-over-standard-prophylaxis-real-world-data-from-the-ahead-german-study/