A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study

Abstract

The development of inhibitory antibodies to factor VIII is a serious complication of hemophilia. FEIBA (factor VIII inhibitorbypassing activity), an activated prothrombin complex concentrate (aPCC), and NovoSeven, recombinant factor VIIa (rFVIIa), are used as hemostatic bypassing agents in treating patients with inhibitors. The FENOC study was designed to test equivalence of the products in the treatment of ankle, knee, and elbow joint bleeding. A prospective, open-label, randomized, crossover, equivalency design was used. The parameters of interest were the percentage of patients who reported efficacy in response to FEIBA and the percentage that reported efficacy in response to NovoSeven. A difference in these percentages of no more than 15% was determined to be a clinically acceptable magnitude for equivalence of the 2 products. The primary outcome was evaluation 6 hours after treatment. Data for 96 bleeding episodes contributed by 48 participants were analyzed. The criterion for declaring the 2 products equivalent at 6 hours was not met; however, the confidence interval of the difference in percentages of efficacy reported for each product only slightly exceeded the 15% boundary (؊11.4%-15.7%), P ‫؍‬ .059. FEIBA and NovoSeven appear to exhibit a similar effect on joint bleeds, although the efficacy between products is rated differently by a substantial proportion of patients. This trial was registered at www.clinicaltrials.gov as #NCT00166309. (Blood. 2007;109:546-551)

Anti-Inhibitor Coagulant Complex Prophylaxis in Hemophilia with Inhibitors

“…Both agents control approximately 80% of bleeding episodes in patients with hemophilia and inhibitors. 4 Nonetheless, their hemostatic efficacy is difficult to predict and does not result in the success rates obtained with factor VIII replacement in patients who have hemophilia without inhibitors. 5 Consequently, patients with inhibitors are at increased risk for bleeding that is difficult to control.…”

Back to the future: a recent history of haemophilia treatment

“…In the context of this much improved but still relatively unsatisfactory background, two approaches have substantially changed the picture: the development of recombinant activated factor VII (rFVIIa) as a new bypassing product and the use of immune tolerance to eradicate the inhibitor, a treatment already pioneered in the early 1980. rFVIIa can stop 80-90% of the spontaneous haemorrhages, particularly when administered early in the home setting [32,33], and elective orthopaedic surgery can be carried out safely [34,35]. The advent of rFVIIa also prompted more studies on FEIBA, which was found to be similar in efficacy and safety to rFVIIa in the context of a randomized trial [36]. One of the limits associated with the use of rFVIIa, i.e.…”

How we treat a hemophilia A patient with a factor VIII inhibitor

“…41 rfVIIa and FEIBA VH have similar efficacy and rates of thrombosis; however, in a prospective randomized comparison of rfVIIa and FEIBA VH, approximately 30% of subjects responded more favorably to one product or the other 6 and 12 hours after treatment. 42 To better tailor treatment in individual patients some have looked to thromboelastography and endogenous thrombin potential. Unfortunately, clinical studies linking these tests with clinical outcomes are lacking 7,43 ; therefore, treatment with rfVIIa and FEIBA VH must be adjusted according to clinical outcomes rather than laboratory testing results.…”