title: 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).
abstract: 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.
authors.affiliation: Children's Hospital Boston, Boston, MA, USA. Ellis.Neufeld@childrens.harvard.edu
authors.forename: E J
authors.initials: EJ
authors.lastname: Neufeld
authors.forename: C M
authors.initials: CM
authors.lastname: Kessler
authors.forename: J C
authors.initials: JC
authors.lastname: Gill
authors.forename: C T
authors.initials: CT
authors.lastname: Wilke
authors.forename: D L
authors.initials: DL
authors.lastname: Cooper
mesh_terms: D000293:Adolescent; D000328:Adult; D019774:Blood Coagulation Factor Inhibitors / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015942:Factor VIIa / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology; D002836:Hemophilia B / Q000188:drug therapy* / Q000276:immunology; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D007223:Infant; D007518:Isoantibodies / Q000276:immunology; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D012042:Registries; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D007518:Isoantibodies; D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa