Recombinant factor VIIa for patients with inhibitors to factor VIII or IX or factor VII deficiency

Inhibitors to factor VIII (FVIII) or IX (FIX) in patients with haemophilia A or B create a challenging problem for the treatment of these patients. Re combinant FVIIa (rFVIIa; NovoSeven(R), Novo Nordisk A/S, Bagsvaerd, Denmark ) is a realistic treatment option, owing to its specific mode of action and lack of immunogenicity. This was a multicentre, open-label, compassionate-use trial in patients wit h severe haemophilia A (FVIII:C < 1%) or B (FIX:C < 1%) with inhibitors, ac quired antibodies to FVIII or FIX, or FVII deficiency (FVII:C < 5%), for wh om alternative therapies had failed or were contraindicated. Patients recei ved rFVIIa treatment for life- or limb-threatening bleeding episodes or for coverage during essential surgery. The mean rFVIIa dose was approximately 90 mu g kg(-1) for haemophilia A/B and acquired inhibitor patients, and 25 mu g kg(-1) for FVII-deficient patients. Efficacy data for 67 treatment epi sodes (45 bleeding episodes, 22 surgical procedures) are presented; seven p atients were treated for a concurrent serious bleeding episode and surgical procedure. At the end of treatment, rFVIIa was effective or partially effe ctive in 85% of serious bleeding episodes. During surgery, bleeding was ass essed as none or less than or equivalent to normal in 91% of surgical proce dures; postoperatively, 91% of procedures were associated with no or minima l oozing. During 60 separate treatment episodes, 26 adverse events (22 nonserious, fo ur serious) were reported in 15 patients, during 17 bleeding episodes or su rgical procedures. Only 10 were considered as having a possible, probable, or unknown relationship with rFVIIa; of these, fever (n=2) and thrombophleb itis (n=3) were the most common. There was no evidence of disseminated intr avascular coagulation. In conclusion, rFVIIa is an effective, well-tolerate d treatment for serious bleeding episodes and bleeding associated with surg ical procedures in patients with severe haemophilia A/B with inhibitors, ac quired inhibitors, or FVII deficiency.