Antigenicity of activated recombinant factor VII followed through nine years of clinical experience

Abstract

Patients treated with activated recombinant factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) were followed for potential antibody formation. The recombinant product was used to control serious and mild-to-moderate bleeds in a hospital environment and mild-to-moderate bleeds at home. The 267 patients included 222 haemophilia A patients, 16 haemophilia B patients, 16 non-haemophilia patients with inhibitors, and 13 factor VII (FVII)-deficient patients. The individual exposure ranged from one to 121 episodes treated over a period of up to 6 years. Analysis for FVII antibodies in an immunoassay revealed that pre-treatment samples from 5% of the haemophilia A patients had values above the normal range. None of these reactions were specific. Increased post-treatment values were observed in two FVII-deficient patients; both patients had been previously treated with plasma-derived FVII. The FVII-specific antibodies reacted equally well with plasma FVII and rFVIIa. The overall result from antibody determination shows no indication of antibody formation against rFVIIa in haemophilia A or B patients or in non-haemophilia patients with acquired inhibitors; however, FVII-deficient patients represent a risk group for development of antibodies against FVII.