Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in hemophilia patients with inhibitors

Abstract

To cite this article: Konkle BA, Ebbesen LS, Erhardtsen E, Bianco RP, Lissitchkov T, Rusen L, Serban MA. Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in hemophilia patients with inhibitors. J Thromb Haemost 2007; 5: 1904-13. Summary. Background: Hemophilic patients with factor VIII (FVIII) and FIX inhibitors suffer from frequent bleeding episodes and reduced quality of life. Objectives: To evaluate whether secondary prophylaxis with activated recombinant factor VII (rFVIIa) can safely and effectively reduce bleeding frequency as compared to conventional on-demand therapy. Methods: Thirty-eight male patients entered a 3-month preprophylaxis period to confirm high baseline bleeding frequency (mean ‡ 4 bleeds per month). Twenty-two patients were randomized 1:1 to receive daily rFVIIa prophylaxis with either 90 or 270 lg kg )1 for 3 months, followed by a 3-month postprophylaxis period. Results: Bleeding frequency was reduced by 45% and 59% during prophylaxis with 90 and 270 lg kg , respectively (P < 0.0001); however, there was no significant difference detected between doses. The majority of this reduction was maintained during the postprophylaxis period. Although all types of bleed were similarly reduced, the effect was most pronounced for spontaneous joint bleeds. Patients reported significantly fewer hospital admissions and days absent from work/school during prophylaxis as compared to the preprophylaxis period. No thromboembolic events were reported during prophylaxis. Conclusion: Clinically relevant reductions in bleeding frequency during prophylaxis as compared to conventional on-demand therapy were achieved without raising safety concerns. These results provide evidence for the concept of secondary rFVIIa prophylaxis in inhibitor patients with frequent bleeds.

Back to the future: a recent history of haemophilia treatment

“…Regular prophylaxis is being considered also in patients with inhibitors, because a randomized study has shown that the prophylactic use of rFVIIa reduces the frequency of bleeding in patients with pre-existing joint damage [68]. The costs involved are exorbitant, but cost-effectiveness may be more favourable in small infants, particularly if less frequent dosing than that used so far to treat bleeding (for instance, once daily or every other day) is efficacious.…”

Redistribution and Hemostatic Action of Recombinant Activated Factor VII Associated with Platelets

“…10 -12 Clinical experience from exploratory phase II trials, however, suggests that the hemostatic action of rFVIIa exceeds its predicted plasma half-life in patients subjected to prophylaxis. [13][14][15] Recent publications have highlighted the potential role of rFVIIa in prophylaxis of hemophilic patients with inhibitors. 14,16,17 Although the mechanisms of action of rFVIIa in the correction of active bleeding have been widely studied, those involved in the apparent long-lasting effects of rFVIIa for prophylactic treatment remain to be clarified.…”

Women leaders in hematology: Inspirations & insights

“…This mentorship was never just scientific; it has been academic, about how to be a woman in this environment, about networking and interacting with peers, and largely about life in general. [49], transfusion medicine, sickle cell disease, and evaluation of the impact of ageing-related health risks, particularly cardiovascular disease, on adults with hemophilia [50,51]. She has a long-standing drive to develop better testing for bleeding and clotting disorders, and is involved in clinical trials of new therapies for hemophilia and von Willebrand disease.…”

“…She has made numerous contributions to the field in the areas of von Willebrand factor modulation in pregnancy and the postpartum period, prevention of postpartum thrombosis, arising issues with hemophilia and aging [50], and the care of patients with hemophilia and inhibitors [49]. She has received federal funding from the NIH and the Centers for Disease Control and Prevention in many of these areas.…”

“…Dr. Konkle, herself, mentioned that she feels her biggest contribution is in clinical research that really touches and improves the lives of patients. Her groundbreaking work on using rFVIIa for secondary prophylaxis in patients with hemophilia and inhibitors highlights just one of the trials that has expanded treatment options for our patients with hemophilia [49]. Her work in establishing a prospective cohort of older patients with moderate and severe hemophilia who will be followed to study aspects of cardiovascular disease [51], and in establishing a genotyping and research repository through the My Life, Our Future study [53] are also going to have significant impacts in the future both for patient care and as research platforms.…”