PharmacoEconomics

, Volume 25, Issue 12, pp 1007–1029 | Cite as

Recombinant Factor VIIa (Eptacog Alfa)

A Pharmacoeconomic Review of its Use in Haemophilia in Patients with Inhibitors to Clotting Factors VIII or IX
  • Katherine A. Lyseng-Williamson
  • Greg L. Plosker
Adis Pharmacoeconomic Drug Evaluation

Abstract

Recombinant factor VIIa (NovoSeven®; also known as recombinant activated factor VII or eptacog alfa) is indicated as an intravenous haemostatic agent in haemophilia patients with inhibitors to clotting factors VIII or IX. In noncomparative trials in haemophilia patients with inhibitors, on-demand home treatment with recombinant factor VIIa was effective in controlling episodes of mild to moderate bleeding and well tolerated, with early treatment being associated with a greater rate of success and the need for fewer doses than delayed treatment. Prophylactic treatment with recombinant factor VIIa was also effective in maintaining haemostasis in patients with this indication undergoing surgery.

Relative to prior treatment with plasma-derived agents, treatment with recombinant factor VIIa was associated with improvements in health-related quality of life in a cost-utility study in haemophilia patients with inhibitors in Australia. In well designed decision-model cost analyses conducted from a healthcare payer perspective in several countries, on-demand treatment with recombinant factor VIIa to control mild to moderate bleeding episodes in this patient population was predicted to be cost saving or cost neutral relative to on-demand treatment with intravenous activated prothrombin complex concentrate (aPCC). Although the acquisition cost of recombinant factor VIIa was greater than that of aPCC in some studies, the greater initial efficacy of recombinant factor VIIa than aPCC resulted in lower predicted total medical costs. Results were generally robust to plausible changes in key parameters.

Orthopaedic surgery with recombinant factor VIIa to maintain haemostasis in haemophilia patients with inhibitors was generally predicted to be cost saving, relative to not having surgery, over the medium to long term in modelled cost analyses from a healthcare payer perspective in the UK and US. The initial cost of surgery was high, but the difference in costs between patients undergoing or not undergoing surgery was predicted to decline over time, as savings were realised from the decrease in the number of bleeding episodes requiring treatment in patients who underwent surgery.

In haemophilia patients with inhibitors, recombinant factor VIIa is clinically effective in controlling mild to moderate bleeds, and in maintaining haemostasis in patients undergoing orthopaedic surgery. Available pharmacoeconomic data from several countries, despite inherent limitations, support the use of recombinant factor VIIa as a treatment option that is at least cost neutral relative to aPCC in treating mild to moderate bleeds in this patient population. In addition, orthopaedic surgery with recombinant factor VIIa to maintain haemostasis in haemophilia patients with inhibitors is generally cost saving relative to not having surgery over the medium to long term, as the acquisition costs of recombinant factor VIIa are offset by cost savings resulting from the decrease in the number of joint-related bleeds.

Keywords

Bleeding Episode Prothrombin Complex Concentrate Pharmacoeconomic Analysis Recombinant Factor VIIa Drug Acquisition Cost 

References

  1. 1.
    World Federation of Hemophilia. Guidelines for the management of hemophilia [online]. Available from URL: http://www.wfh.org [Accessed 2007 Oct 1]Google Scholar
  2. 2.
    United Kingdom Haemophilia Centre Doctors’ Organisation (UKHCDO). Guidelines on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders. Haemophilia 2003 Jan; 9 (1): 1–23CrossRefGoogle Scholar
  3. 3.
    Mathew P. Current opinion on inhibitor treatment options. Semin Hematol 2006; 43 Suppl. 4: S8–S13PubMedCrossRefGoogle Scholar
  4. 4.
    Berntorp E, Shapiro A, Astermark J, et al. Inhibitor treatment in haemophilias A and B: summary statement for the 2006 international consensus conference. Haemophilia 2006; 12 Suppl. 6: 1–7PubMedCrossRefGoogle Scholar
  5. 5.
    European Medicines Agency. NovoSeven (eptacog alfa): summary of product characteristics [online]. Available from URL: http://www.emea.europa.eu [Accessed 2007 Oct 1]Google Scholar
  6. 6.
    NovoSeven® (coagulation factor Vila [recombinant]): US prescribing information. Princeton (NJ): Novo Nordisklnc, 2006 Oct 13Google Scholar
  7. 7.
    Siddiqui MA, Scott LJ. Recombinant factor Vila (eptacog alfa): a review of its use in congenital or acquired haemophilia and other congenital bleeding disorders. Drugs 2005; 65 (8): 1161–1177PubMedCrossRefGoogle Scholar
  8. 8.
    FEIBA (VH anti-inhibitor coagulant complex, vapor heated): US prescribing information. Westlake Village (CA): Baxter Healthcare Corporation, 2005 AprGoogle Scholar
  9. 9.
    Monahan PE, Aledort LM. Factors affecting choice of hemostatic agent for the hemophilia patient with an inhibitor antibody. Am J Hematol 2004 Dec; 77 (4): 346–350PubMedCrossRefGoogle Scholar
  10. 10.
    Hay CR, Baglin TP, Collins PW, et al. The diagnosis and management of factor VIII and IX inhibitors: a guideline from the UK Haemophilia Centre Doctors’ Organization (UKHCDO). Br J Haematol 2000 Oct; 111 (1): 78–90PubMedCrossRefGoogle Scholar
  11. 11.
    DiMichele DM, Hoots WK, Pipe SW, et al. International workshop on immune tolerance induction: consensus recommendations. Haemophilia 2007 Jul; 13 Suppl. 1: 1–22PubMedCrossRefGoogle Scholar
  12. 12.
    Konkle BA, Ebbesen LS, Erhardtsen E et al. Randomized, prospective clinical trial of recombinant factor Vila for secondary prophylaxis in hemophilia patients with inhibitors. J Thromb Haemost 2007 Sep; 5 (9): 1904–1913PubMedCrossRefGoogle Scholar
  13. 13.
    Morfini M, Auerswald G, Kobelt RA, et al. Prophylactic treatment of haemophilia patients with inhibitors: clinical experience with recombinant factor Vila in European haemophilia centres. Haemophilia 2007 Sep; 13 (5): 502–507PubMedCrossRefGoogle Scholar
  14. 14.
    Bolton-Maggs PHB, Pasi KJ. Haemophilias A and B. Lancet 2003; 361: 1801–1809PubMedCrossRefGoogle Scholar
  15. 15.
    Knight C. Health economics of treating haemophilia A with inhibitors. Haemophilia 2005 Nov; 11 Suppl. 1: 11–17PubMedCrossRefGoogle Scholar
  16. 16.
    Mejia-Carvajal C, Czapek EE, Valentino LA. Life expectancy in hemophilia outcome. J Thromb Haemost 2006 Mar; 4 (3): 507–509PubMedCrossRefGoogle Scholar
  17. 17.
    Morfini M, Haya S, Tagariello G, et al. European study on orthopaedic status of haemophilia patients with inhibitors. Haemophilia 2007 Sep; 13 (5): 606–612PubMedCrossRefGoogle Scholar
  18. 18.
    Seal one L, Mantovani LG, Mannucci PM, et al. Quality of life is associated to the orthopaedic status in haemophilic patients with inhibitors. Haemophilia 2006; 12 (2): 154–162CrossRefGoogle Scholar
  19. 19.
    Rogoff EG, Guirguis HS, Lipton RA, et al. The upward spiral of drug costs: a time series analysis of drugs used in the treatment of hemophilia. Thromb Haemost 2002 Oct; 88 (4): 545–553PubMedGoogle Scholar
  20. 20.
    Goudemand J. Treatment of patients with inhibitors: cost issues. Haemophilia 1999 Nov; 5 (6): 397–401PubMedCrossRefGoogle Scholar
  21. 21.
    Chang H, Sher GD, Blanchette VS, et al. The impact of inhibitors on the cost of clotting factor replacement therapy in haemophilia A in Canada. Haemophilia 1999 Jul; 5 (4): 247–252PubMedCrossRefGoogle Scholar
  22. 22.
    Gautier P, D’Alche-Gautier MJ, Coatmelec B, et al. Cost related to replacement therapy during hospitalization in haemophiliacs with or without inhibitors: experience of six French haemophilia centres. Haemophilia 2002 Sep; 8 (5): 674–679PubMedCrossRefGoogle Scholar
  23. 23.
    Gringeri A, Mantovani LG, Scalone L, et al. Cost of care and quality of life for patients with hemophilia complicated by inhibitors: the COCIS Study Group. Blood 2003 Oct 1; 102 (7): 2358–2363PubMedCrossRefGoogle Scholar
  24. 24.
    Ingerslev J, Thykjær H, Scheibel E. Approaches towards successful home treatment in patients with inhibitors. Eur J Haematol 1998; 61: 11–14CrossRefGoogle Scholar
  25. 25.
    Key NS, Aledort LM, Beardsley D, et al. Home treatment of mild to moderate bleeding episodes using recombinant factor Vila (Novoseven) in haemophiliacs with inhibitors. Thromb Haemost 1998; 80 (6): 912–918PubMedGoogle Scholar
  26. 26.
    Santagostino E, Gringeri A, Mannucci PM. Home treatment with recombinant activated factor VII in patients with factor VIII inhibitors: the advantages of early intervention. Br J Haematol 1999; 104: 22–26PubMedCrossRefGoogle Scholar
  27. 27.
    Lusher JM. Recombinant activated factor VII for treatment of intramuscular haemorrhages: a comparison of early versus late treatment. Blood Coagul Fibrinolysis 1998; 9 Suppl. 1: S111–S114Google Scholar
  28. 28.
    Lusher JM. Acute hemarthroses: the benefits of early versus late treatment with recombinant activated factor VII. Blood Coagul Fibrinolysis 2000 Apr; 11 Suppl. 1: S45–S49PubMedCrossRefGoogle Scholar
  29. 29.
    Kavakli K, Makris M, Zulfikar B, et al. 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 (4): 600–605PubMedGoogle Scholar
  30. 30.
    Santagostino E, Mancuso ME, Rocino A, et al. A prospective randomized trial of high and standard dosages of recombinant factor Vila for treatment of hemarthroses in hemophiliacs with inhibitors. J Thromb Haemost 2006 Feb; 4 (2): 367–371PubMedCrossRefGoogle Scholar
  31. 31.
    Astermark J, Donfield SM, DiMichele DM, et al. A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) study. Blood 2007; 109 (2): 546–551PubMedCrossRefGoogle Scholar
  32. 32.
    Dundar S, Zulfikar B, Kavakli K, et al. A cost evaluation of treatment alternatives in mild-to-moderate bleeding episodes in haemophilia patients with inhibitors in Turkey. J Med Econ 2005; 8: 45–54CrossRefGoogle Scholar
  33. 33.
    Hart WM. An economic evaluation of NovoSeven in the management of haemophilia patients with inhibitors in Slovakia [abstract no. POD1]. Value Health 2002 Nov–Dec; 5 (6): 576–577. Plus poster presented at the 5th Annual European Congress of the International Society for Pharmacoeconomics and Outcomes Research; 2002 Nov 3–5; RotterdamCrossRefGoogle Scholar
  34. 34.
    Ozelo MC, Villaca PR, De Almeida JO, et al. A cost evaluation of treatment alternatives for mild-to-moderate bleeding episodes in patients with haemophilia and inhibitors in Brazil. Haemophilia 2007 Sep; 13 (5): 462–469PubMedCrossRefGoogle Scholar
  35. 35.
    Plyush O, Kopylov K, Zozulya N, et al. A cost evaluation of treament alternatives in mild-to-moderate bleeding episodes in haemeophilia patients with inhibitors in Russia [in Russian]. Paediatr Haematol Oncol Immunopathol 2006; 5 (3): 16–22Google Scholar
  36. 36.
    Yoo SK, Yong LS, Kyu PS, et al. Pharmaco-economic evaluation of treatment alternatives for mild to moderate bleeding episodes in patients with haemophilia with inhibitors in Korea [abstract no. P-W-158 plus poster]. 21st Congress of the International Society on Thrombosis and Haemostasis; 2007 Jul 6–12; GenevaGoogle Scholar
  37. 37.
    Hilgartner M, Aidedort L, Andes A, et al. Efficacy and safety of vapor-heated anti-inhibitor coagulant complex in haemophilia patients. Transfusion (Paris) 1990 Sep; 30 (7): 626–630CrossRefGoogle Scholar
  38. 38.
    Odeyemi IAO, Guest JF. Modelling the economic impact of recombinant activated factor VII compared to activated prothrorribin-complex concentrate in the home treatment of a mild to moderate bleed in adults with inhibitors to clotting factors VIII and IX in the UK. J Med Econ 2002; 5: 119–133CrossRefGoogle Scholar
  39. 39.
    Odeyemi IAO, Guest JF. Modelling the economic impact of recombinant activated factor VII and activated prothrorribin-complex concentrate in the treatment of a mild to moderate bleed in adults with inhibitors to clotting factors VIII and IX at a comprehensive care centre in the UK. J Med Econ 2002; 5: 51–64CrossRefGoogle Scholar
  40. 40.
    Shapiro AD, Gilchrist GS, Hoots WK, et al. Prospective, randomised trial of two doses of rFVIIa (NovoSeven) in haemophilia patients with inhibitors undergoing surgery. Thromb Haemost 1998; 80: 773–778PubMedGoogle Scholar
  41. 41.
    Ingerslev J, Freidman D, Gastineau D, et al. Major surgery in haemophilic patients with inhibitors using recorribinant factor Vila. Haemostasis 1996 Jan; 26: 118–123PubMedGoogle Scholar
  42. 42.
    Ingerslev J. Efficacy and safety of recorribinant factor Vila in the prophylaxis of bleeding in various surgical procedures in hemophilic patients with factor VIII and factor IX inhibitors. Semin Thromb Hemost 2000; 26 (4): 425–432PubMedCrossRefGoogle Scholar
  43. 43.
    Lusher J, Ingerslev J, Roberts H, et al. Clinical experience with recombinant factor Vila. Blood Coagul Fibrinolysis 1998; 9 (2): 119–128PubMedCrossRefGoogle Scholar
  44. 44.
    Scharrer I. Recombinant factor Vila for patients with inhibitors to factor VIII or IX or factor VII deficiency. Haemophilia 1999 Jul; 5 (4): 253–259PubMedCrossRefGoogle Scholar
  45. 45.
    Abshire T, Kenet G. Recombinant factor Vila: review of efficacy, dosing regimens and safety in patients with congenital and acquired factor VIII or IX inhibitors. J Thromb Haemost 2004 Jun; 2 (6): 899–909PubMedCrossRefGoogle Scholar
  46. 46.
    Roberts HR, Monroe DM, White GC. The use of recorribinant factor Vila in the treatment of bleeding disorders. Blood 2004 Dec 15; 104 (13): 3858–3864PubMedCrossRefGoogle Scholar
  47. 47.
    O’Connell KA, Wood JJ, Wise RP, et al. Thromboembolic adverse events after use of recombinant human coagulation factor Vila. JAMA 2006 Jan 18; 295 (3): 293–298PubMedCrossRefGoogle Scholar
  48. 48.
    Ekert H, Brewin T, Boey W, et al. Cost-utility analysis of recombinant factor Vila (NovoSeven) in six children with long-standing inhibitors to factor VIII or IX. Haemophilia 2001 May; 7 (3): 279–285PubMedCrossRefGoogle Scholar
  49. 49.
    Knight C, Paisley S, Wight J, et al. Economic modelling of different treatment strategies for haemophilia A with high-responding inhibitors. Haemophilia 2003 Jul; 9 (4): 521–540PubMedCrossRefGoogle Scholar
  50. 50.
    Huth-Kuehne A, Lages P, Zimmermann R. The impact of rebleeds in cost modelling of treatment strategies in patients with hemophilia A and inhibitors [abstract no. 4046]. Blood 2006; 108 (11 Pt 2): 90bGoogle Scholar
  51. 51.
    Joshi AV, Stephens JM, Munro V, et al. Pharmacoeconomic analysis of recombinant factor Vila versus APCC in the treatment of minor-to-moderate bleeds in hemophilia patients with inhibitors. Curr Med Res Opin 2006 Jan; 22 (1): 23–31PubMedCrossRefGoogle Scholar
  52. 52.
    Putnam KG, Bohn RL, Ewenstein BM, et al. A cost minimization model for the treatment of minor bleeding episodes in patients with haemophilia A and high-titre inhibitors. Haemophilia 2005 May; 11 (3): 261–269PubMedCrossRefGoogle Scholar
  53. 53.
    Steen Carlsson K, Astermark J, Donfield SM, et al. Health-economic analysis of alternative bypassing agents in haemophilia complicated by an inhbitor: the FEIBA® NovoSeven® comparative study (FENOC) [abstract no. 457]. Blood 2006 Nov 1; 108 (11 Pt. 1): 139Google Scholar
  54. 54.
    Odeyemi I. The economic impact of anamnestic response to treatment in haemophilia patients with inhibitors [abstract no. P0876]. Haemophilia 2006; 12 Suppl. 2: 133. Plus poster presented at the World Federation of Haemophilia; 2006 May 21–25; Vancouver (BC)CrossRefGoogle Scholar
  55. 55.
    Ballal R, Joshi AV, Stephens JM, et al. Lifetime economic value of orthopedic surgery with recorribinant activated factor VII in hemophilia patients with inhibitors [abstract no. PHM6]. Value Health 2007 May–June; 10 (3): A154. Plus poster presented at the 12th Annual Congress of the International Society for Pharmacoeconomics and Outcomes Research; 2007 May 19–23; Arlington (VA)CrossRefGoogle Scholar
  56. 56.
    Botteman MF, Ballal R, Joshi A. Economic benefits of knee surgery with recombinant activated factor VII in hemophilia patients with inhibitors [abstract no. P-M-171 plus poster]. 21st Congress of the International Society on Thrombosis and Haemostasis; 2007 Jul 6–12; GenevaGoogle Scholar
  57. 57.
    Green C, De Cock E. Cost-consequences of orthopaedic surgery in haemophilia patients with inhibitors [abstract no. POD4]. Value Health 2001 Nov–Dec; 4 (6): 467. Plus poster presented at the 4th Annual European Conference of the International Society for Pharmacoeconomics and Outcomes Research; 2001 Nov 11–13; CannesCrossRefGoogle Scholar
  58. 58.
    Bonnet P, Yoon B, Ewenstein B, et al. Hemophilia patients with inhibitors undergoing major orthopedic surgeries: cost-minimization analysis of activated prothrombin complex concentrate (APCC) and recombinant FVIIA [abstract no. P-M-169]. 21st Congress of the International Society on Thrombosis and Haemostasis; 2007 Jul 6–12; GenevaGoogle Scholar
  59. 59.
    Jonsson B. Changing health environment: the challenge to demonstrate cost-effectiveness of new compounds. Pharmacoeconomics 2004; 22 Suppl. 4: 5–10PubMedCrossRefGoogle Scholar
  60. 60.
    Seremetis S, Joshi AV, Asmussen M. Cost minimization model for treatment of minor bleeding episodes in inhibitor patients: methodological issues [letter]. Haemophilia 2006 Jan; 12 (1): 108–109PubMedCrossRefGoogle Scholar
  61. 61.
    Stephens JM, Joshi AV, Sumner M, et al. Health economic review of recombinant activated factor VII for treatment of bleeding episodes in hemophilia patients with inhibitors. Expert Opin Pharmacother 2007 Jun; 8 (8): 1127–1136PubMedCrossRefGoogle Scholar
  62. 62.
    Allen G, Aledort L. Therapeutic decision-making in inhibitor patients. Am J Hematol 2006 Jan; 81 (1): 71–72PubMedCrossRefGoogle Scholar
  63. 63.
    Aledort LM. Comparative thrombotic event incidence after infusion of recombinant factor Vila versus factor VIII inhibitor bypass activity. J Thromb Haemost 2004 Oct; 2 (10): 1700–1708PubMedCrossRefGoogle Scholar
  64. 64.
    Bohn RL, Aledort LM. Post-marketing surveillance of thrombotic events among users of rFVUa and FEIBA: how costly are these adverse events? [abstract no. P0824]. J Thromb Haemost 2005 Aug 1; 3 Suppl. 1Google Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • Katherine A. Lyseng-Williamson
    • 1
    • 2
  • Greg L. Plosker
    • 1
    • 2
  1. 1.Wolters Kluwer Health ¦ AdisMairangi Bay, North Shore 0754, AucklandNew Zealand
  2. 2.an editorial office of Wolters KluwerConshohockenUSA

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