Efficacy and inhibitor development in previously treated patients with haemophilia A switched to a B domain-deleted recombinant factor VIII

Abstract

There have been recent reports of unexpected poor efficacy of a B-domain-deleted recombinant factor VIII (BDD-rFVIII) in haemophiliacs, and inhibitor development in previously treated patients (PTPs) switched to BDD-rFVIII. The results of a 6-month prospective study of 25 PTPs and of a retrospective survey of 94 PTPs, all switched to BDD-rFVIII, were used to evaluate efficacy and inhibitor development. The prospective study showed that 89% of 362 bleeds were controlled by one to two infusions, reproducing the efficacy profiles of other recombinant products (rFVIIIs). One patient, previously treated with plasma-derived FVIII only, developed a high titre inhibitor (30 BU) after 5 days of exposure. The retrospective survey, carried out in the total Italian PTP population switched to BDD-rFVIII, involved 19 PTPs at higher inhibitor risk due to previous exposure of ≤ 50 days and 75 PTPs at lower inhibitor risk due to previous exposure of >50 days. One patient developed an inhibitor: he was a high-risk, severe PTP previously exposed to another rFVIII for 3 days only. Among the entire low-risk population of severe Italian PTPs switched to BDD-rFVIII (25 in the prospective study, 49 in the retrospective cohort) only one developed an inhibitor (1-3%). These data indirectly support the views that BDD-rFVIII is equivalent to other rFVIIIs in term of efficacy and inhibitor development.