title: Cumulative inhibitor incidence in previously untreated patients with severe hemophilia A treated with plasma-derived versus recombinant factor VIII concentrates: a critical systematic review.
abstract: Inhibitor development represents currently the most serious and challenging complication of clotting factor replacement therapy. A number of studies have analyzed the impact of the type of factor VIII (FVIII) replacement therapy (plasma-derived versus recombinant concentrates) on inhibitor development in hemophilia A patients with conflicting results. In order to shed light on this controversial issue, we performed a systematic review and meta-analysis on the published prospective studies evaluating the incidence rate of inhibitors in previously untreated patients (PUPs) with severe hemophilia A. Data from a total of 800 patients enrolled in 25 prospective studies published between 1990 and 2007 were included in this review. The quality of the studies was evaluated using two different systems: the Newcastle-Ottawa Scale (NOS) and STrengthening the Reporting of OBservational studies in Epidemiology (STROBE). Overall, the inhibitor incidence rate did not differ significantly between recipients of plasma-derived and recombinant FVIII concentrates (weighted means: 21%; 95% CI, 14-30 versus 27%; 95% CI, 21-33). Similarly, high titer inhibitors did not differ significantly between patients treated with plasma-derived (weighted means: 14%; 95% CI, 8-25) or recombinant FVIII concentrates (weighted means: 16%; 95% CI, 13-20). Thus, the main conclusion of this systematic review performed using selective criteria is that the type of FVIII product (i.e., plasma-derived versus recombinant FVIII concentrates) does not seem to influence the inhibitor rate in PUPs with severe hemophilia A.
authors.affiliation: Immunohematology and Transfusion Center, Department of Laboratory and Pathology Medicine, University Hospital of Parma, Via Gramsci 14, Parma, Italy. mfranchini@ao.pr.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Franchini
authors.forename: Annarita
authors.initials: A
authors.lastname: Tagliaferri
authors.forename: Carlo
authors.initials: C
authors.lastname: Mengoli
authors.forename: Mario
authors.initials: M
authors.lastname: Cruciani
mesh_terms: D019774:Blood Coagulation Factor Inhibitors / Q000032:analysis* / Q000378:metabolism; D005169:Factor VIII / Q000276:immunology / Q000302:isolation & purification* / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D010949:Plasma / Q000737:chemistry*; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D011994:Recombinant Proteins; D005169:Factor VIII