Exposure and safety of higher doses of recombinant factor VIIa ≥250 μg kg −1 in individuals with congenital haemophilia complicated by alloantibody inhibitors: the Haemophilia and Thrombosis Research Society Registry experience (2004–2008)

Summary.  Recombinant factor VIIa (rFVIIa) is a well‐established treatment for managing bleeding episodes in individuals with congenital haemophilia complicated by alloantibody inhibitors (CHwI). The safety and efficacy of standard dosing (90–120 μg kg −1 every 2–3 h) are well‐established; however, the desire to optimize therapy with one or more higher doses instead of multiple lower doses has created a need for evidence of the safety and efficacy of such regimens. Analysis of data from the Haemophilia and Thrombosis Research Society (HTRS) Registry was performed on episodes where doses of ≥250 μg kg −1 were reported. From 2041 rFVIIa‐treated bleeds, 172 bleeding episodes were identified in 25 individuals with CHwI who were treated with ≥1 higher doses (≥250 μg kg −1 , ≥270 μg kg −1 or ≥300 μg kg −1 ) of rFVIIa between January 2004 and November 2008. Bleeds occurred in individuals ranging in age from 0.4 to 41.7 years who were predominantly non‐Hispanic and white (40%) with haemophilia A (88%). Bleed types most frequently treated with higher doses of rFVIIa were spontaneous (62–65%) or traumatic (27–32%). Bleed locations most frequently treated with higher doses of rFVIIa were joint (60–68%) or muscle (20–25%). A total of 1521 rFVIIa doses were administered (median, three doses per bleed); 26% were 250 μg kg −1 or higher (initial dose, 82%). Bleeding stopped in 93% (160/172) of bleeds treated with rFVIIa 250 μg kg −1 or higher. No serious adverse drug‐related events or thrombotic complications were reported. This data analysis from the HTRS Registry provides evidence of the safe and effective use of higher doses of rFVIIa (≥250 μg kg −1 ) in US practice.