title: French previously untreated patients with severe hemophilia A after exposure to recombinant factor VIII : incidence of inhibitor and evaluation of immune tolerance.
abstract: Fifty French previously untreated patients with severe hemophilia A (factor VIII < 1%), treated with only one brand of recombinant factor VIII (rFVIII), were evaluated for inhibitor development, assessment of risk factors and outcome of immune tolerance regimen. The median period on study was 32 months (range 9-74) since the first injection of rFVIII. Fourteen patients (28%) developed an inhibitor, four of whom (8%) with a high titer (> or = 10 BU). All inhibitor patients but one continued to receive rFVIII either for on-demand treatment or for immune tolerance regimen (ITR). Among these patients, inhibitor was transient in 2 (4%), became undetectable in 6 and was still present in 6. The prevalence of inhibitor was 12%. Presence of intron 22 inversion was found to be a risk factor for inhibitor development. Immune tolerance was difficult to achieve in our series despite a follow-up period of 16 to 30 months: immune tolerance was complete in only one out of the 3 patients undergoing low dose ITR and in one out of the 5 patients with high dose ITR.
authors.affiliation: Hemophilia Center of Paris-Necker, Bicêtre, France.
authors.forename: C
authors.initials: C
authors.lastname: Rothschild
authors.forename: Y
authors.initials: Y
authors.lastname: Laurian
authors.forename: E P
authors.initials: EP
authors.lastname: Satre
authors.forename: A
authors.initials: A
authors.lastname: Borel Derlon
authors.forename: H
authors.initials: H
authors.lastname: Chambost
authors.forename: P
authors.initials: P
authors.lastname: Moreau
authors.forename: J
authors.initials: J
authors.lastname: Goudemand
authors.forename: A
authors.initials: A
authors.lastname: Parquet
authors.forename: J
authors.initials: J
authors.lastname: Peynet
authors.forename: M
authors.initials: M
authors.lastname: Vicariot
authors.forename: P
authors.initials: P
authors.lastname: Beurrier
authors.forename: S
authors.initials: S
authors.lastname: Claeyssens
authors.forename: A
authors.initials: A
authors.lastname: Durin
authors.forename: A
authors.initials: A
authors.lastname: Faradji
authors.forename: E
authors.initials: E
authors.lastname: Fressinaud
authors.forename: S
authors.initials: S
authors.lastname: Gaillard
authors.forename: V
authors.initials: V
authors.lastname: Guérin
authors.forename: C
authors.initials: C
authors.lastname: Guérois
authors.forename: G
authors.initials: G
authors.lastname: Pernod
authors.forename: P
authors.initials: P
authors.lastname: Pouzol
authors.forename: J F
authors.initials: JF
authors.lastname: Schved
authors.forename: C
authors.initials: C
authors.lastname: Gazengel
mesh_terms: D002648:Child; D002675:Child, Preschool; D007446:Chromosome Inversion; D005169:Factor VIII / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D005500:Follow-Up Studies; D005602:France; D006467:Hemophilia A / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007108:Immune Tolerance; D007114:Immunization; D007223:Infant; D007438:Introns / Q000235:genetics; D007518:Isoantibodies / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D012307:Risk Factors
chemical_list: D007518:Isoantibodies; D011994:Recombinant Proteins; C078147:F8 protein, human; D005169:Factor VIII