Effect of rFVIIa dose and time to treatment on patients with haemophilia and inhibitors: analysis of HemoRec registry data from the Czech Republic

Abstract

Identifying haemophilia patients with inhibitors for clinical trials is difficult due to the limited number of patients available. Registries are therefore being established as an additional means of data collection. The aim of this study was to investigate the effect of different recombinant activated factor VII (rFVIIa; NovoSeven dose ranges and dosing schedules on the incidence of re-bleeding in haemophilia patients with inhibitors. In this retrospective, uncontrolled study, data on the bleeding patterns of adult haemophilia patients with high responding inhibitors were analysed. Only data from the Czech Republic, obtained by the HemoRec registry, were used. This study analysed 'real-life' clinical data and focused on the collection of the same parameters in different patients: time from bleeding onset to first injection, effect of first injection, number of re-bleedings, total number of injections and total amount of haemostatic drug used. Fifteen patients met the inclusion criteria and were included into the study (128 bleeding episodes). Patients treated within 2 h of bleeding onset experienced less re-bleeding than patients treated after 2 h of bleeding onset (5.2% vs. 13.7%, respectively). In addition, patients who were treated after 2 h of bleeding onset experienced fewer re-bleedings when high-dose rFVIIa was used (15.8% and 0%; <120 microg kg(-1) and >250 microg kg(-1), respectively). Initial high-dose rFVIIa was also associated with a decline in total rFVIIa consumption. This registry has provided a unique insight into the bleeding patterns of inhibitor patients, highlighting the importance of early treatment initiation and appropriate starting dose.

Advances in bypassing agent therapy for hemophilia patients with inhibitors to close care gaps and improve outcomes

“…The importance of early initiation of effective treatment was clearly demonstrated in data from a prospective, observational registry established in 2005. Data reported from the Czech Republic included 15 inhibitor patients treated with rFVIIa for 128 bleeding episodes [Salaj et al 2009]. In patients treated within 2 hours after the appearance of the first symptoms, 5.2% experienced rebleeding, whereas in those treated more than 2 hours after symptom onset, 13.7% experienced rebleeding.…”

“…Long-term follow up demonstrated a correlation between the number of hemarthroses and the joint score as a measure of joint damage [Manco-Johnson et al 2007;Nilsson et al 1992], thus supporting the concept of prevention of hemarthroses through prophylactic administration of FVIII/ FIX concentrates as a mechanism to ameliorate associated sequelae. It is also widely recognized that treatment initiated at the first signs of a hemorrhagic episode results in more efficient hemostasis and is often associated with the need for fewer required overall doses of replacement therapy [Salaj et al 2009;Lusher, 1998b]. The establishment of home-based treatment has facilitated early replacement therapy and set the stage for the administration of optimal prophylaxis.…”

Registry‐based outcome assessment in haemophilia: a scoping study to explore the available evidence

“…Outcome of treatment of a bleeding event is one of the most important aspects of haemophilia care, although there is no consensus as to how to report it. The HemoRec registry reported on different indexes of bleeding treatment outcome [27][28][29][30]. Because bleeding events are generally patientreported outcomes, efforts should be made to reduce the amount of information by focusing on the most important questions.…”

“…Of these, four registries included the number of joint bleeding events whilst only three noted TJ. In three of the four papers reported on TJ, the definition used was missing [28,30,43]. Arthropathy and ROM were each reported by two registries.…”

“…The HemoRec registry also reported on outcomes of treatment of bleeding events. Measures including time to resolution [27][28][29], effectiveness of treatment [27] and rebleeding [27,28,30] were introduced to evaluate treatment efficiency. The PedNet registry introduced the extent of bleed as an outcome measure [31].…”