Real-World Early Treatment with Room Temperature–Stable Recombinant Factor VIIa in Hemophilia A/B and Inhibitors: SMART-7™ Post Hoc Analyses

Francesco Demartis; Angelika Batorova; Hervé Chambost; Peyman Eshghi; Mehran Karimi; Kaan Kavakli; Soraya Benchikh El Fegoun; Katarina Cepo; Lene Sommer Vestergaard; Gary Benson

doi:10.1055/s-0037-1608943

TH Open, Inhaltsverzeichnis

CC-BY 4.0 · TH Open 2017; 01(02): e130-e138
DOI: 10.1055/s-0037-1608943

Original Article

Georg Thieme Verlag KG Stuttgart · New York

Real-World Early Treatment with Room Temperature–Stable Recombinant Factor VIIa in Hemophilia A/B and Inhibitors: SMART-7™ Post Hoc Analyses

Francesco Demartis

¹Agenzia per l'Emofilia, Centro Malattie Emorragiche, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy

,

Angelika Batorova

²National Hemophilia Centre, Department of Hematology and Transfusion Medicine, Medical School of Comenius University, University Hospital, Bratislava, Slovakia

,

Hervé Chambost

³Service d'Hématologie Oncologie Pédiatrique, La Timone, APHM, and Inserm, UMR 1062, Faculté de Médecine, Aix-Marseille Université, Marseille, France

,

Peyman Eshghi

⁴Pediatric Congenital Hematologic Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

,

Mehran Karimi

⁵Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

,

Kaan Kavakli

⁶Department of Hematology, Ege University Children's Hospital, Izmir, Turkey

,

Soraya Benchikh El Fegoun

⁷Biopharm Operations, Novo Nordisk Healthcare AG, Zurich, Switzerland

,

Katarina Cepo

⁸Medical & Science Biopharm, Novo Nordisk A/S, Søborg, Denmark

,

Lene Sommer Vestergaard

⁹Biostatistics LCM Haem, GH & Concizumab, Novo Nordisk A/S, Søborg, Denmark

,

Gary Benson

¹⁰Northern Ireland Haemophilia Comprehensive Care Centre, Belfast City Hospital, Belfast, United Kingdom

› Institutsangaben

Abstract

Treating hemophilia A or B patients with inhibitors is particularly challenging, as they do not respond to replacement therapy with factor VIII or factor IX concentrates. A room temperature–stable formulation of recombinant activated factor VII (rFVIIa; NovoSeven^®), which provides improved convenience and treatment access to patients compared with the earlier formulation of rFVIIa, was shown to be safe and effective in a post-authorization, multinational, observational study (Study Monitoring Antibodies against Room Temperature–stable factor 7 [SMART-7™]). In post hoc, subgroup analyses of SMART-7™ data, the hemostatic response following rFVIIa monotherapy in patients with hemophilia A or B with inhibitors by time to first treatment and in different age cohorts was assessed. A total of 482/618 bleeding episodes treated with rFVIIa monotherapy and with (1) valid efficacy assessment, (2) no missing time for bleed start, (3) no missing time for any dose administration, and (4) valid time to first treatment were included in the analyses. Data on the type and location of bleeding episodes treated with rFVIIa monotherapy were also collected. The majority of bleeding episodes treated with rFVIIa monotherapy were treated within 1 hour after bleeding onset (318/482 [66%]) and, among them, 96.5% (307/318) were effectively treated (i.e., bleeding stopped). Hemostatic efficacy remained high for bleeding episodes treated >1 to ≤4 hours after the onset, with 94/101 (93.1%) treated effectively. Cause and location of bleeding varied across the different age groups assessed. Real-world evidence from post hoc, subgroup analyses of SMART-7™ data confirmed that patients were able to treat themselves quickly and that early treatment with rFVIIa was associated with high efficacy.

Keywords

bleeding - efficacy - eptacog alfa activated - NovoSeven^® - rFVIIa

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Referenzen

References
1 Persson E, Bolt G, Steenstrup TD, Ezban M. Recombinant coagulation factor VIIa--from molecular to clinical aspects of a versatile haemostatic agent. Thromb Res 2010; 125 (06) 483-489
2 Hedner U. Factor VIIa and its potential therapeutic use in bleeding-associated pathologies. Thromb Haemost 2008; 100 (04) 557-562
3 Butros L, Boayue K, Mathew P. Current difficulties and recent advances in bypass therapy for the management of hemophilia with inhibitors: a new and practical formulation of recombinant factor VIIa. Drug Des Devel Ther 2011; 5: 275-282
4 Bysted BV, Scharling B, Møller T, Hansen BL. A randomized, double-blind trial demonstrating bioequivalence of the current recombinant activated factor VII formulation and a new robust 25 degrees C stable formulation. Haemophilia 2007; 13 (05) 527-532
5 European Medicines Agency. NovoSeven Summary of Product Characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000074/WC500030873.pdf . Accessed May 24, 2017
6 Novo Nordisk. FDA Approves NOVO NORDISK's NovoSeven® RT (Coagulation Factor VIIa [Recombinant] Room Temperature Stable) for Hemophilia Patients with Inhibitors. Available at: http://press.novonordisk-us.com/News-Releases?item=122388
7 Kavakli K, Demartis F, Karimi M. , et al. Safety and effectiveness of room temperature stable recombinant factor VIIa in patients with haemophilia A or B and inhibitors: results of a multinational, prospective, observational study. Haemophilia 2017; 23 (04) 575-582
8 Key NS, Aledort LM, Beardsley D. , et al. Home treatment of mild to moderate bleeding episodes using recombinant factor VIIa (NovoSeven) in haemophiliacs with inhibitors. Thromb Haemost 1998; 80 (06) 912-918
9 Shapiro AD, Gilchrist GS, Hoots WK, Cooper HA, Gastineau DA. Prospective, randomised trial of two doses of rFVIIa (NovoSeven) in haemophilia patients with inhibitors undergoing surgery. Thromb Haemost 1998; 80 (05) 773-778
10 Srivastava A, Brewer AK, Mauser-Bunschoten EP. , et al; Treatment Guidelines Working Group on Behalf of The World Federation Of Hemophilia. Guidelines for the management of hemophilia. Haemophilia 2013; 19 (01) e1-e47
11 Ljung R, Chambost H, Stain AM, DiMichele D. Haemophilia in the first years of life. Haemophilia 2008; 14 (Suppl. 03) 188-195
12 Miesbach W, Alesci S, Krekeler S, Seifried E. Comorbidities and bleeding pattern in elderly haemophilia A patients. Haemophilia 2009; 15 (04) 894-899
13 Tagliaferri A, Di Perna C, Rivolta GF. Secondary prophylaxis in adolescent and adult haemophiliacs. Blood Transfus 2008; 6 (Suppl. 02) s17-s20
14 Parameswaran R, Shapiro AD, Gill JC, Kessler CM. ; HTRS Registry Investigators. Dose effect and efficacy of rFVIIa in the treatment of haemophilia patients with inhibitors: analysis from the Hemophilia and Thrombosis Research Society Registry. Haemophilia 2005; 11 (02) 100-106
15 Chambost H, Santagostino E, Laffan M, Kavakli K. ; ONE Registry Steering Committee on behalf of the investigators. Real-world outcomes with recombinant factor VIIa treatment of acute bleeds in haemophilia patients with inhibitors: results from the international ONE registry. Haemophilia 2013; 19 (04) 571-577
16 Santagostino E, Escobar M, Ozelo M. , et al. Recombinant activated factor VII in the treatment of bleeds and for the prevention of surgery-related bleeding in congenital haemophilia with inhibitors. Blood Rev 2015; 29 (Suppl. 01) S9-S18
17 Salaj P, Brabec P, Penka M. , et al. Effect of rFVIIa dose and time to treatment on patients with haemophilia and inhibitors: analysis of HemoRec registry data from the Czech Republic. Haemophilia 2009; 15 (03) 752-759
18 Kavakli K, Makris M, Zulfikar B, Erhardtsen E, Abrams ZS, Kenet G. ; NovoSeven trial (F7HAEM-1510) investigators. Home treatment of haemarthroses using a single dose regimen of recombinant activated factor VII in patients with haemophilia and inhibitors. A multi-centre, randomised, double-blind, cross-over trial. Thromb Haemost 2006; 95 (04) 600-605
19 Santagostino E, Mancuso ME, Rocino A, Mancuso G, Scaraggi F, Mannucci PM. A prospective randomized trial of high and standard dosages of recombinant factor VIIa for treatment of hemarthroses in hemophiliacs with inhibitors. J Thromb Haemost 2006; 4 (02) 367-371
20 Young G, Shafer FE, Rojas P, Seremetis S. Single 270 microg kg(-1)-dose rFVIIa vs. standard 90 microg kg(-1)-dose rFVIIa and APCC for home treatment of joint bleeds in haemophilia patients with inhibitors: a randomized comparison. Haemophilia 2008; 14 (02) 287-294
21 Knight C, Danø AM, Kennedy-Martin T. Systematic review of efficacy of rFVIIa and aPCC treatment for hemophilia patients with inhibitors. Adv Ther 2009; 26 (01) 68-88
22 Lusher JM. Early treatment with recombinant factor VIIa results in greater efficacy with less product. Eur J Haematol Suppl 1998; 63: 7-10
23 Lusher JM. Acute hemarthroses: the benefits of early versus late treatment with recombinant activated factor VII. Blood Coagul Fibrinolysis 2000; 11 (Suppl. 01) S45-S49
24 Salek SZ, Benson GM, Elezović I. , et al. The need for speed in the management of haemophilia patients with inhibitors. Haemophilia 2011; 17 (01) 95-102
25 Gruppo RA, Kessler CM, Neufeld EJ, Cooper DL. Assessment of individual dose utilization vs. physician prescribing recommendations for recombinant activated factor VII (rFVIIa) in paediatric and adult patients with congenital haemophilia and alloantibody inhibitors (CHwI): the Dosing Observational Study in Hemophilia (DOSE). Haemophilia 2013; 19 (04) 524-532