Pediatric Clinics of North America - CIPERJ

370 RODRIGUEZ & HOOTS
Fig. 3. Schematic model showing the domain structure of factor VIII (FVIII) and the localization
of the main binding epitopes of FVIII antibodies. (From Astermark J. Basic aspects of
inhibitors to factors VIII and IX and the influence of non-genetic risk factors. Haemophilia
2006;12(Suppl 6):8–13; with permission.)
recently, Gringeri and colleagues [38] reported the results of the first prospective
ITI study using a VWF-containing factor VIII concentrate in patients
who had hemophilia A considered at high risk for a poor response to ITI.
This study showed successful inhibitor eradication in 9 of the 16 (53%) patients
who completed this study. The median time to inhibitor eradication
was 24 months (range 4–30 months). The remaining seven patients showed
partial success documented by a decreased inhibitor titer (median of
1.5 BU, range 1.1–2.8 BU), without complete disappearance. One patient
was withdrawn 12 months after enrollment as a result of persistent high-titer
inhibitor (70 BU). Overall, this study demonstrated a relatively high success
rate of inhibitor eradication, taking into consideration that this group of patients
was at high risk for a poor response and two of them previously had
failed ITI.
Rituximab experience in hemophilia with inhibitors
Rituximab, a human-mouse chimeric monoclonal antibody directed
against the CD20 antigen, has demonstrated a therapeutic benefit in the
treatment of B-cell–mediated malignancies and immune-mediated disorders,
such as immune thrombocytopenic purpura and autoimmune hemolytic
anemia [39–41]. The use of rituximab in acquired hemophilia versus congenital
hemophilia is reported more extensively [42,43]. The standard dose for
rituximab use in hemophilia has been 375 mg/m 2 /dose, administered weekly
for 4 weeks and then monthly (up to 5 months) until the inhibitor
disappears.
Rituximab has been used in congenital hemophilia with inhibitors in only
18 documented patients (12 who had severe hemophilia A, four who had
mild or moderate hemophilia A, and two who had severe hemophilia B).
Thirteen of them responded favorably to rituximab, three with a complete
response and 10 with a partial response, whereas the remaining five patients
had no response [42,43]. The data suggest that the efficacy of rituximab may
be enhanced by concomitant administration of factor VIII. The long-term
success of such an approach is not clear, however, as further follow-up is
needed.