Safety of recombinant activated factor VII ( rFVII a) in patients with congenital haemophilia with inhibitors: overall rFVII a exposure and intervals following high (>240 μg kg −1 ) rFVII a doses across clinical trials and registries

• Published in: Haemophilia : the official journal of the World Federation of Hemophilia Vol. 20; no. 1
• Main Authors: Shapiro, A. D., Neufeld, E. J., Blanchette, V., Salaj, P., Gut, R. Z., Cooper, D. L.
• Format: Journal Article
• Language: English
• Published: 01-01-2014
• ISSN: 1351-8216; 1365-2516
• DOI: 10.1111/hae.12329

Summary
Recombinant activated factor VII (
rFVII
a) is indicated for treatment of bleeding in congenital haemophilia with inhibitors (CHwI) using 90 μg kg
−1
every 2–3 h (EU and US) or a single 270 μg kg
−1
dose (EU only) with ~90% efficacy reported for both regimens. Dosing of
rFVII
a varies, and home treatment makes assessment of frequency of doses >90 μg kg
−1
, the intervals before additional treatment, and the risk for thromboembolic events (TEs) more difficult. This
post hoc
analysis assessed the safety and distribution of
rFVII
a dosing in CHwI and the impact of >240 μg kg
−1
dosing on subsequent bypassing agent (BPA) dosing interval and frequency. Data regarding on‐demand or prophylactic
rFVII
a dosing, TE incidence and subsequent BPA dosing after high
rFVII
a doses were compiled from multiple sources incorporating safety surveillance. A total of 61 734
rFVII
a doses were reported in 481 patients treated for 3947 bleeds and for 43 135 prophylaxis days. Over half (52%) exceeded 120 μg kg
−1
, 37% exceeded 160 μg kg
−1
and 15% exceeded 240 μg kg
−1
. Subsequent doses of BPA(s) were administered after 38% of initial and 49% of any
rFVII
a dose >240 μg kg
−1
, and were most frequently administered ≥24 h after initial (40%) or any (53%) doses >240 μg kg
−1
. No TEs were reported. The findings of this analysis show that
rFVII
a doses >90 μg kg
−1
are utilized for ‘real‐world’ treatment of children and adults. When additional BPA was administered following an
rFVII
a dose >240 μg kg
−1
, reported intervals were prolonged, often ≥24 h. No safety issues were identified in the 61 734 doses analysed.