title: Efficacy, safety and tolerability of recombinant factor VIII (REFACTO) in patients with haemophilia A: interim data from a postmarketing surveillance study in Germany and Austria.
abstract: An open-label, multicentre, postmarketing surveillance study conducted in Germany and Austria with recombinant factor VIII (REFACTO) has enrolled 217 patients (mean age 26.3 years) from 38 haemophilia centres during the first 4.8 years. Most patients (188/217; 86.6%) had severe to moderately severe haemophilia A, of whom 153 completed sufficient diary information for the main efficacy analysis. These 153 patients experienced a median of 6.6 (interquartile range 1.4-18.6) bleeding episodes per year. Patients treated with prophylaxis experienced a median of 4.4 (1.1-9.3) bleeds per year, while patients treated on-demand experienced a median of 22.8 (11.3-29.0) bleeds per year. Overall, most physicians (41/43 [95.3%]) were 'very satisfied' or 'satisfied' with the efficacy of REFACTO in the treatment of bleeding episodes. A total of 137 non-serious adverse events have been reported in 52/217 patients (24.0%) to date. In addition, 129 serious adverse events in 87 patients (40%) were reported, including 41 cases of 'less than expected therapeutic effect' (LETE). Of these, 39 LETE cases were reported in one centre; however, patients in this centre experienced considerably fewer bleeding episodes per year than patients outside this centre. Overall, six patients (2.8%) have developed de novo inhibitors, three of which were considered high titre. Four of these patients were at high risk (0-50 exposure days [ED]) of inhibitor formation, one was at intermediate risk (51-100 ED) and one was at low risk (>100 ED). These results emphasize the benefit of postmarketing surveillance and, overall, this study confirms the efficacy, safety and tolerability of REFACTO in the treatment of patients with haemophilia A.
authors.affiliation: Institut für Thrombophilie und Hämostaseologie, Münster, Germany. pollmann@haemophilie-zentrum.de
authors.forename: H
authors.initials: H
authors.lastname: Pollmann
authors.forename: D
authors.initials: D
authors.lastname: Externest
authors.forename: A
authors.initials: A
authors.lastname: Ganser
authors.forename: B
authors.initials: B
authors.lastname: Eifrig
authors.forename: W
authors.initials: W
authors.lastname: Kreuz
authors.forename: H
authors.initials: H
authors.lastname: Lenk
authors.forename: I
authors.initials: I
authors.lastname: Pabinger
authors.forename: W
authors.initials: W
authors.lastname: Schramm
authors.forename: T F
authors.initials: TF
authors.lastname: Schwarz
authors.forename: R
authors.initials: R
authors.lastname: Zimmermann
authors.forename: N
authors.initials: N
authors.lastname: Zavazava
authors.forename: J
authors.initials: J
authors.lastname: Oldenburg
authors.forename: R
authors.initials: R
authors.lastname: Klamroth
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D001317:Austria; D002648:Child; D002675:Child, Preschool; D003029:Coagulants / Q000009:adverse effects*; D005169:Factor VIII / Q000009:adverse effects*; D005858:Germany; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012308:Risk Management; D016896:Treatment Outcome
chemical_list: D003029:Coagulants; C427184:recombinant factor VIII SQ; D005169:Factor VIII