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

Summary Recombinant activated factor VII (rFVIIa) 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 rFVIIa 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 rFVIIa 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 rFVIIa dosing, TE incidence and subsequent BPA dosing after high rFVIIa doses were compiled from multiple sources incorporating safety surveillance. A total of 61 734 rFVIIa 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 rFVIIa 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 rFVIIa doses >90 μg kg−1 are utilized for ‘real-world’ treatment of children and adults. When additional BPA was administered following an rFVIIa dose >240 μg kg−1, reported intervals were prolonged, often ≥24 h. No safety issues were identified in the 61 734 doses analysed.