Cumulative inhibitor incidence in previously untreated patients with severe hemophilia A treated with plasma-derived versus recombinant factor VIII concentrates: a critical systematic review.

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.