title: Source and purity of factor VIII products as risk factors for inhibitor development in patients with hemophilia A.
abstract: BACKGROUND
  Inhibitor development is influenced by several factors and the type of factor VIII (FVIII) products may play a role.
  
  
  OBJECTIVE
  In order to explore such a role, we designed a cohort study whose novelty resides in the classification of products not only according to the source of FVIII (plasmatic, pd, or recombinant, r) but also to their degree of purity (expressed as specific activity).
  
  
  METHODS
  Treatment data up to inhibitor development or 150 exposure days were collected in 377 patients with hemophilia A.
  
  
  RESULTS
  Inhibitors developed in 111 patients (29%; 96 high-responders, 25%). The cumulative incidence was progressively higher from patients treated with low/intermediate-purity pdFVIII compared with those treated with high-purity pd and rFVIII. The adjusted hazard ratio of inhibitor development was 4.9 with rFVIII and 2.0 with high-purity pdFVIII (95% CI, 2.9-8.3 and 1.1-4.0), taking as reference low/intermediate-purity pdFVIII. There was no difference in the frequency of inhibitor testing between treatment groups. Sensitivity analyses (in patients who never switched product type, previously untreated patients, those treated on-demand and those with high-risk F8 mutations) confirmed an increased inhibitor risk with rFVIII and high-purity pdFVIII.
  
  
  CONCLUSIONS
  This study shows that the degree of purity of FVIII products influences inhibitor development independently from other risk factors, and emphasizes that differences exist within pdFVIII products.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan, Milan, Italy. elisamancuso@tiscali.it
authors.forename: M E
authors.initials: ME
authors.lastname: Mancuso
authors.forename: P M
authors.initials: PM
authors.lastname: Mannucci
authors.forename: A
authors.initials: A
authors.lastname: Rocino
authors.forename: I
authors.initials: I
authors.lastname: Garagiola
authors.forename: A
authors.initials: A
authors.lastname: Tagliaferri
authors.forename: E
authors.initials: E
authors.lastname: Santagostino
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood*; D002648:Child; D003029:Coagulants / Q000009:adverse effects / Q000032:analysis / Q000276:immunology* / Q000627:therapeutic use*; D005169:Factor VIII / Q000009:adverse effects / Q000032:analysis / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D005838:Genotype; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016016:Proportional Hazards Models; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D003029:Coagulants; D011994:Recombinant Proteins; D005169:Factor VIII