Adverse Events in Treatment of Inherited Factor VII Deficiency: Final Analysis of the STER.

No evidence-based guidelines are available for the treatment of Factor VII deficiency. Replacement therapy (RT) is still influenced by different factors as rarity of the disorder, availability and supply of products and economic reasons. All RTs are not exempt of side effects and scanty data is available about the safety of the products currently used. Aim of this study was to analyze adverse events (AEs) of RTs for congenital Factor VII deficiency, as reported in Seven Treatment Evaluation Registry (STER).

FVII deficiency patients treated for bleeding episodes, prophylaxis, and surgery were investigated for RT-related AEs over a period of 8 years. STER is a prospective, observational, multicenter, web-based registry created to collect and describe data on treatment modalities and outcomes in patients with this rare bleeding disorder. Decisions on type of RT and schedules were autonomously taken by enrolling physicians. The STER reported the following information: AE clinical description, evaluation (serious or not), and potential association with the type of treatment adopted (likely, unlikely). Any AE was evaluated at the time of treatment and after 30 days or more if needed.

STER enrolled 223 patients for 308 different treatments with the following products: recombinant activated Factor VII (rFVIIa, n=241), plasma-derived Factor VII concentrates (pdFVII, n=31), Fresh Frozen Plasma (FFP, n=30),Prothrombin Complex Concentrate (PCC, n=5) and one case treated with Factor Eight Inhibitor Bypass Agent (FEIBA). Overall, fifteen AEs were recorded in 11 patients (8 M, 3 F; mean age: 31,7 y; range: 4m–75): twelve (80%) occurred in a surgical setting (n=138) while three (20%) for treatments for bleeding episodes (n=116). Among the individuals with reported AEs, 14 received rFVIIa and 1 was given pdFVII. Nine AEs were judged as likely related and six as unlikely related to the product.

One AE event was life-threatening, seven were reported as serious, and seven as not serious. Likely-related AEs were the following: thrombosis (n=4;1 arterial thrombosis, 1 Superficial Vein Thrombosis, 2 Cerebral Infarctions), 2 cases of inhibitor development and 3 other (headache, hypertension and mild re-bleeding). In detail, inhibitor occurred in 2/125 (1.6%) of those in whom a centralized screening could be done, both high responders (20 and 10.4 BU max titres), one following pdFVII and one after rFVIIa (both previously exposed to pdFVII and FFP). All thrombotic episodes followed surgery.

In the STER, AEs mainly occurred in surgical patients with an ovarall prevalence of thrombosis of < 4%. Inhibitor development occurred in less than 2% of the study population, in previously exposed patients. Finally, AE were not reported to significantly affect the patient's management.

Mariani:Novonordisk: Consultancy, Honoraria. Ingerslev:Novonordisk: Consultancy.