title: Systematic review of the role of FVIII concentrates in inhibitor development in previously untreated patients with severe hemophilia a: a 2013 update.
abstract: Nowadays, patients with hemophilia A receive a high standard of care; therefore, the most challenging complication of factor VIII (FVIII) replacement therapy has become the development of FVIII inhibitors, which render the concentrate infusion ineffective and expose patients to an increased risk of morbidity and mortality. Among environmental risk factors influencing inhibitor development, the type of FVIII products has always drawn the attention of investigators. Conflicting results are reported in the literature concerning rates of inhibitor development after either plasma-derived or recombinant FVIII concentrates. To help elucidate this controversial issue, we have performed a systematic review and meta-analysis of prospective studies evaluating the incidence of inhibitors in previously untreated patients with severe hemophilia A receiving plasma-derived or recombinant FVIII products. The quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS), the STrenghtening the Reporting of OBservational studies in Epidemiology and an ad hoc quality score. Overall, 28 prospective studies, including 1,421 patients with hemophilia A, fulfilled our selection criteria and were included in the systematic review. No statistically significant differences were observed in the inhibitor incidence between plasma-derived and recombinant FVIII concentrates considering all (weighted means: 23%, 95% CI: 15-33% vs. 29%, 95% CI: 26-32%) and high titer (16%, 95% CI: 10-26% vs. 18%, 95% CI: 15-21%) inhibitors. Similarly, no significant differences were found in the inhibitor incidence among the different classes of recombinant products. In conclusion, the results of our meta-analysis show that the different types of FVIII products are not associated with different risks of inhibitor development.
authors.affiliation: Department of Transfusion Medicine and Hematology, Carlo Poma Hospital, Mantova, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Franchini
authors.forename: Antonio
authors.initials: A
authors.lastname: Coppola
authors.forename: Angiola
authors.initials: A
authors.lastname: Rocino
authors.forename: Elena
authors.initials: E
authors.lastname: Santagostino
authors.forename: Annarita
authors.initials: A
authors.lastname: Tagliaferri
authors.forename: Ezio
authors.initials: E
authors.lastname: Zanon
authors.forename: Massimo
authors.initials: M
authors.lastname: Morfini
mesh_terms: D005169:Factor VIII / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000276:immunology; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D005169:Factor VIII