Abstract Number: PB1035
Meeting: ISTH 2020 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: Extended half-life (EHL) factor VIII (FVIII) requires improvements in half-life (t1/2) and area under the curve (AUC) of 1.3 and 1.25 times compared to standard half-life (SHL) products.
Aims: The aim of this study is compare pharmacokinetics (PK) after the switch from SHL to EHL in hemophilia A (HA) patients.
Methods: Multicenter comparative, cross-sectional, prospective study analyzing PK differences after switch from SHL to EHL (efmoroctocog-alfa [rFVIII-Fc] and rurioctocog-alfa pegol [PEG-rFVIII]). WAPPS-Hemo® was used to analyze PK parameters: t1/2; AUC, peak level, trough level at 24, 48, 72 h and time to reach FVIII levels of 1, 2, 5%. Ratio of t1/2and AUC, nº weekly doses, dose/kg/week, annual bleeding rate (ABR) and annual joint bleeding rate (AJBR) before/after the switch were compared. Wilcoxon and Kruskal-Wallis tests (SPSS®) were employed.
Results: Eighty-seven patients from 8 Spanish hospitals were analyzed (62 rFVIII-Fc; 25 PEG-rFVIII), 83 had severe HA and 4 moderate HA, with a median age of 30 years (range=3-64).
All PK parameters were improved, ABR and AJBR were reduced, as well as dose/kg/week (16.9%, IQR:8.7-32.8%) and weekly infusion frequency (30%, IQR:0-33.3%) (Tables 1-2). In 14 younger patients the dose/kg/week was increased a median of 28.6% (IQR:11.7-40-7%). The median ratios of t1/2 and AUC were 1.4 (IQR:1.3-1.6) and 1.7 (IQR:1.3-2.2) in the entire cohort. In patients with ≥12 years treated with EHL ratios of t1/2 and AUC were 1.4 (IQR:1.3-1.7) and 1.8 (IQR:1.3-2.3), and in patients < 12 years treated with rFVIII-Fc were 1.3 (IQR:0.9-1.5) and 1.4 (IQR:1.1-2.1). No differences were observed in PK parameters in patients aged ≥12 years treated with rFVIII-Fc vs. PEG-rFVIII (Tables 1-2).
Conclusions: EHL FVIII have shown significant PK improvements, reductions in ABR and AJBR, avoiding one weekly infusion number and dose/kg/week. Outside the clinical trial setting, we have observed an increase in t1/2 and AUC ratios accordingly to EHL definition.
PK parameters | SHL: median (IQR) | EHL: median (IQR) | P-value | rFVIII-Fc (n=46): median (IQR) | PEG-rFVIII (n=25): median (IQR) | P-value |
t1/2 (h) | 12.5 (9.5-15.8) | 18.3 (13.3-23.5) | <0.001 | 20.3 (15.0-23.8) | 19.8 (14.8-23.8) | 0.736 |
AUC ((IU*h)/L) | 9166 (7082-12349) | 15805 (12184-21930) | <0.001 | 16456 (12682-21930) | 17811 (13072-25327) | 0.613 |
Peak level (IU/dL) | 70.5 (56.8-81.0) | 80.0 (68.0-97.5) | <0.001 | 76.0 (63.0-95.0) | 94.0 (72.0-99.0) | 0.099 |
Trough level at 24h | 13.1 (9.2-18.8) | 24.6 (19.9-34.6) | <0.001 | 26.7 (20.7-34.6) | 31.7 (22.7-39.9) | 0.295 |
Trough level at 48h | 3.9 (2.0-7.1) | 9.9 (5.9-17.4) | <0.001 | 10.8 (8.1-17.9) | 14.9 (6.7-19.6) | 0.576 |
Trough level at 72h | 1.5 (0.9-3.0) | 4.1 (2.1-8.5) | <0.001 | 5.0 (2.9-8.5) | 7.0 (2.3-9.4) | 0.880 |
T5% | 43.3 (33.0-58.8) | 66.0 (51.5-91.0) | <0.001 | 71.9 (59.0-91.5) | 83.0 (52.6-93.9) | 0.970 |
T2% | 63.4 (48.5-80.3) | 93.0 (72.3-126.0) | <0.001 | 103.4 (82.0-127.4) | 112.8 (74.9-129.8) | 0.802 |
T1% | 84.0 (67.9-109.8) | 122.5 (92.6-160.3) | <0.001 | 136.5 (106.0-163.1) | 143.8 (96.8-166.6) | 0.634 |
[Table 1. Comparisons between PK parameters after the switch between SHL to EHL FVIII (entire cohort) and between EHLs (patients aged ≥12 years).]
Clinical variables | SHL: median (IQR) | EHL: median (IQR) | P-value | rFVIII-Fc (N=46): median (IQR) | PEG-rFVIII (N=25): median (IQR) | P-value |
Age (years) | Not evaluated | Not evaluated | Not evaluated | 33.5 (19.0-46.0) | 37.0 (30.0-42.0) | 0.665 |
Weigh (kg) | 70 (55-84) | 70 (57-87) | 0.055 | 72 (64-90) | 82 (72-94) | 0.132 |
Nº weekly doses | 3.0 (2.0-3.0) | 2.0 (1.8-2.3) | <0.001 | 2.0 (1.8-2.3) | 2.0 (2.0-2.3) | 0.831 |
Dose (IU/kg/week) | 74.5 (58.0-105.2) | 65.7 (44.8-96.5) | <0.001 | 60.5 (43.0-87.0) | 51.7 (44.7-67.4) | 0.191 |
ABR (N=47) | 2.0 (0.0-5.0) | 0.0 (0.0-2.0) | 0.001 | 1.0 (0.0-3.5) | 0.0 (0.0-0.0) | 0.148 |
AJBR (N=26) | 1.0 (0.0-4.0) | 0.0 (0.0-1.0) | 0.007 | 1.0 (0.0-1.0) | 0.0 (0.0-0.0) | 0.373 |
[Table 2. Comparisons between clinical variables after the switch between SHL to EHL FVIII (entire cohort) and between EHLs (patients aged ≥12 years).]
To cite this abstract in AMA style:
Megías-Vericat JE, Bonanad S, Martínez García MF, Berrueco R, Mingot-Castellano EM, Rodríguez López M, Canaro Hirnyk M, Mateo Arranz J, Calvo Villas JM, Haya S, Benitez O, Mesegué Medea M, Albo López C, Palomero-Massanet A, Vilalta Seto N, Larrodé Leciñena I, Cid AR, Poveda JL. Pharmacokinetic and Clinical Improvements after PK-guided Switch from Standard Half-life to Extended Half-life Factor VIII Products [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/pharmacokinetic-and-clinical-improvements-after-pk-guided-switch-from-standard-half-life-to-extended-half-life-factor-viii-products/. Accessed September 27, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/pharmacokinetic-and-clinical-improvements-after-pk-guided-switch-from-standard-half-life-to-extended-half-life-factor-viii-products/