title: Safety and efficacy of sucrose-formulated full-length recombinant factor VIII: experience in the standard clinical setting.
abstract: The safety of full-length sucrose-formulated recombinant factor VIII (rFVIII-FS; Kogenate FS) for up to 24 months of use was evaluated in a postmarketing observational study in Europe. Long-term safety and efficacy data were available for 212 patients with severe haemophilia A, including 13 previously untreated patients (PUPs) and 12 patients with 1-19 exposure days (EDs). Patients accumulated a mean (+/- SD) of 187 (121) EDs to rFVIII-FS and received a total of 39,627 infusions, mainly for prophylaxis and for the treatment of 4,283 spontaneous or trauma-related bleeds during an average observation time of 710 (136) days. Of these bleeding episodes, 85.4% were successfully treated with one or two infusions of rFVIII-FS. Haemostasis was also evaluated during 46 minor to major surgical procedures, and the response to infusion was "excellent" or "good" in all cases. FVIII inhibitor formation was observed in six patients (two de novo; four persistent or recurrent). The de novo cases represent 8.0% (2 of 25) of patients who reported 0-19 previous EDs at study entry. Four of the five patients who reported possible drug-related adverse effects developed inhibitors. The results of this observational study demonstrate the efficacy and safety of rFVIII-FS during normal clinical use in the treatment of patients with severe haemophilia A. Furthermore, these findings are consistent with those of previous phase III clinical studies with rFVIII-FS, particularly with regard to its efficacy and low incidence of inhibitor formation.
authors.affiliation: Azienda Ospedale Vittorio Emanuele, Ospedale Ferrarotto, Catania, Italy, rmusso.ematol@tiscalinet.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Musso
authors.forename: Elena
authors.initials: E
authors.lastname: Santagostino
authors.forename: Albert
authors.initials: A
authors.lastname: Faradji
authors.forename: Alfonso
authors.initials: A
authors.lastname: Iorio
authors.forename: Jan
authors.initials: J
authors.lastname: van der Meer
authors.forename: Jørgen
authors.initials: J
authors.lastname: Ingerslev
authors.forename: Thierry
authors.initials: T
authors.lastname: Lambert
authors.forename: Monika
authors.initials: M
authors.lastname: Maas-Enriquez
authors.forename: Eduard
authors.initials: E
authors.lastname: Gorina
mesh_terms: D000293:Adolescent; D000328:Adult; D019774:Blood Coagulation Factor Inhibitors / Q000097:blood; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D002626:Chemistry, Pharmaceutical; D002648:Child; D002675:Child, Preschool; D003029:Coagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005060:Europe; D005079:Excipients / Q000737:chemistry*; D005169:Factor VIII / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy*; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007223:Infant; D007263:Infusions, Parenteral; D008297:Male; D011358:Product Surveillance, Postmarketing; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012720:Severity of Illness Index; D013395:Sucrose / Q000737:chemistry*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D003029:Coagulants; D005079:Excipients; D011994:Recombinant Proteins; D013395:Sucrose; C078147:F8 protein, human; D005169:Factor VIII