title: Efficacy and inhibitor development in previously treated patients with haemophilia A switched to a B domain-deleted recombinant factor VIII.
abstract: There have been recent reports of unexpected poor efficacy of a B-domain-deleted recombinant factor VIII (BDD-rFVIII) in haemophiliacs, and inhibitor development in previously treated patients (PTPs) switched to BDD-rFVIII. The results of a 6-month prospective study of 25 PTPs and of a retrospective survey of 94 PTPs, all switched to BDD-rFVIII, were used to evaluate efficacy and inhibitor development. The prospective study showed that 89% of 362 bleeds were controlled by one to two infusions, reproducing the efficacy profiles of other recombinant products (rFVIIIs). One patient, previously treated with plasma-derived FVIII only, developed a high titre inhibitor (30 BU) after 5 days of exposure. The retrospective survey, carried out in the total Italian PTP population switched to BDD-rFVIII, involved 19 PTPs at higher inhibitor risk due to previous exposure of < or = 50 days and 75 PTPs at lower inhibitor risk due to previous exposure of > 50 days. One patient developed an inhibitor: he was a high-risk, severe PTP previously exposed to another rFVIII for 3 days only. Among the entire low-risk population of severe Italian PTPs switched to BDD-rFVIII (25 in the prospective study, 49 in the retrospective cohort) only one developed an inhibitor (1.3%). These data indirectly support the views that BDD-rFVIII is equivalent to other rFVIIIs in term of efficacy and inhibitor development.
authors.affiliation: Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre and Department of Internal Medicine and Dermatology, IRCCS Maggiore Hospital and University of Milan, Milan. alessandro.gringeri@unimi.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gringeri
authors.forename: Annarita
authors.initials: A
authors.lastname: Tagliaferri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tagariello
authors.forename: Massimo
authors.initials: M
authors.lastname: Morfini
authors.forename: Elena
authors.initials: E
authors.lastname: Santagostino
authors.forename: Piermannuccio
authors.initials: P
authors.lastname: Mannucci
mesh_terms: D000293:Adolescent; D000328:Adult; D019774:Blood Coagulation Factor Inhibitors / Q000032:analysis*; D002648:Child; D005169:Factor VIII / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000627:therapeutic use*; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy*; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D019774:Blood Coagulation Factor Inhibitors; C427184:recombinant factor VIII SQ; D005169:Factor VIII