Thrombotic events with recombinant activated factor VII (rFVIIa) in approved indications are rare and associated with older age, cardiovascular disease, and concomitant use of activated prothrombin complex concentrates (aPCC)
Received 15 June 2019
Accepted for publication 23 August 2019
Published 18 September 2019 Volume 2019:10 Pages 335—340
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Dr Martin Bluth
Madhvi Rajpurkar,1 Stacy E Croteau,2 Lisa Boggio,3 David L Cooper4
1Carman and Ann Adams Department of Pediatrics, Children’s Hospital of Michigan/Wayne State University, Detroit, MI, USA; 2Department of Pediatrics, Boston Children’s Hospital/Harvard Medical School, Boston, MA, USA; 3Hemophilia and Thrombophilia Center, Rush University Medical Center, Chicago, IL, USA; 4Clinical Development and Medical Affairs – Biopharm, Novo Nordisk Inc., Plainsboro, NJ, USA
Correspondence: Madhvi Rajpurkar
Carman and Ann Adams Department of Pediatrics, Children’s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd, Detroit, MI 48201, USA
Tel +1 313 745 5515
Fax +1 313 745 5237
Purpose: Recombinant activated factor VII (rFVIIa; NovoSeven® RT; Novo Nordisk A/S, Bagsvaerd, Denmark) is approved in the United States for the treatment of bleeding and perioperative management in congenital hemophilia with inhibitors (CHwI), acquired hemophilia (AH), congenital factor VII (FVII) deficiency, and Glanzmann’s thrombasthenia (GT) with refractoriness to platelets. The aim of the current analysis was to review clinical trials and registries pre- and post-licensure for each indication to establish the estimated rate of thrombosis and then to establish the association of all reported thrombotic events (TEs) with certain risk factors listed for many years in the prescribing information (PI).
Patients and methods: A retrospective safety assessment of both clinical trials and registries used to support licensure and postmarketing surveillance was performed. The rate of thrombosis was calculated in the 4 indicated disorders and an assessment of TE risk factors was conducted through a review of all narratives within those indications in the safety database.
Results: In clinical trials and registries used to support licensure and in postmarketing surveillance, the overall rate of thrombosis was 0.17% of 12,288 bleeding and surgical episodes. The specific risk by indication was 0.11% for CHwI, 0.82% for FVII deficiency, 0.19% for GT, and 1.77% for AH. The most common associated risk factor—“elderly” (29%), defined in the PI as age ≥65 years—was particularly prevalent in patients with AH. TE was also frequently reported with concomitant cardiac or vascular disease (18%) and use of activated prothrombin complex concentrates (18%).
Conclusion: Data show that the rate of TEs within the 4 licensed indications is low, as was originally described in the US PI from 1999 to 2009. It has remained stable over time during postapproval surveillance in multiple US and global registries with active surveillance for safety information across the 4 approved indications.
Keywords: postmarketing surveillance, acquired hemophilia, congenital hemophilia with inhibitors, congenital factor VII deficiency, Glanzmann’s thrombasthenia
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