title: Safety and efficacy of solvent/detergent-treated antihaemophilic factor with an added 80 degrees C terminal dry heat treatment in patients with haemophilia A.
abstract: Plasma-derived factor VIII concentrates remain an important resource for haemophilia A patients. To improve the safety of these preparations, various methods of viral removal and inactivation have been used that are designed to eliminate both enveloped and non-enveloped viruses. There have been rare reports that some viral inactivation processes altered the immunogenicity of some concentrates, leading to the development of factor VIII inhibitors in previously treated haemophilia A patients. This study evaluated the safety, efficacy and lack of neo-antigenicity of a highly purified factor VIII preparation which undergoes both solvent/detergent treatment and final dry heat treatment at 80 degrees C for 72 h. The study included: (i) a single blind, single-dose crossover pharmacokinetic study in 18 previously treated patients, comparing sibling lots of the unheated preparation (Koate(R)-HP) and the heat-treated preparation (Koate(R)-DVI), and (ii) an extended home treatment programme for 36 patients at two haemophilia treatment centres primarily to assess immunogenicity. Clinical parameters were assessed at regular intervals. The results confirm that Koate(R)-HP and Koate(R)-DVI are bioequivalent, and that Koate(R)-DVI is safe and efficacious for treatment of acute bleeding episodes and for surgery. Furthermore, the heat-treated preparation is not associated with the development of inhibitors in previously treated patients.
authors.affiliation: University of California Davis Hemophilia Treatment Center, Sacramento, CA 95817, USA. jspowell@ucdavis.edu
authors.forename: J S
authors.initials: JS
authors.lastname: Powell
authors.forename: M
authors.initials: M
authors.lastname: Bush
authors.forename: J
authors.initials: J
authors.lastname: Harrison
authors.forename: C
authors.initials: C
authors.lastname: Abildgaard
authors.forename: E
authors.initials: E
authors.lastname: Vosburgh
authors.forename: A R
authors.initials: AR
authors.lastname: Thompson
authors.forename: D
authors.initials: D
authors.lastname: Hurst
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016063:Blood Loss, Surgical / Q000517:prevention & control; D016001:Confidence Intervals; D003257:Consumer Product Safety; D018592:Cross-Over Studies; D003902:Detergents / Q000494:pharmacology*; D005169:Factor VIII / Q000276:immunology / Q000493:pharmacokinetics / Q000592:standards* / Q000627:therapeutic use*; D006467:Hemophilia A / Q000150:complications / Q000628:therapy* / Q000821:virology; D006470:Hemorrhage / Q000517:prevention & control / Q000628:therapy; D018718:Home Infusion Therapy / Q000009:adverse effects / Q000592:standards; D006358:Hot Temperature / Q000627:therapeutic use*; D006801:Humans; D007518:Isoantibodies / Q000097:blood; D008297:Male; D008875:Middle Aged; D012698:Serologic Tests; D012997:Solvents / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D003902:Detergents; D007518:Isoantibodies; D012997:Solvents; D005169:Factor VIII