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

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.