Prophylaxis in clinical practice

Inhibitor patients present a difficult challenge1,2

Patients with inhibitors are at greater risk for difficult-to-treat complications that may disrupt their daily lives—and can lead to life-threatening situations.

  • Increased risk of uncontrolled bleeds1,2
  • Greater morbidity
  • Haemophilic arthropathy, orthopaedic complications, and pain can be more severe, and quality of life can be impacted3,4
  • Variable response to bypassing agents2,5,6
  • In some cases, even a small number of bleeding episodes in a single joint can contribute to irreversible joint alterations that lead progressively to haemophilic arthropathy.5-7

Prophylaxis with bypassing therapy is increasingly used for haemophilia patients with inhibitors9

  • The recognized benefits of long-term prophylaxis in haemophilia patients without inhibitors has led many clinicians to consider the use of prophylaxis with bypassing agents for haemophilia patients with inhibitors10,11
  • For inhibitor patients, prophylaxis has the potential to decrease the patient's use of medical resources and improve quality of life10

Prophylaxis is considered the standard of care for severe haemophilia patients without inhibitors3, 12-14

  • Primary prophylaxis for severe haemophilia is a recommendation of the World Health Organization, the US National Hemophilia Foundation (US), and the World Federation of Hemophilia3, 12-14
  • Prophylaxis has been shown to decrease joint bleeding with preservation of joint function and improvement in quality of life. It is also cost-effective in the long-term because it eliminates the high cost associated with subsequent management of damaged joints.12

FEIBA is recommended for prophylaxis

Two recent, prospective, randomised clinical studies demonstrated the merits of FEIBA as an efficacious prophylaxis therapy.16 In these two studies, FEIBA prophylaxis also provided some corresponding quality-of-life (QoL) improvement trends (ns).16-19

The Pro-FEIBA Study was an investigator-initiated, prospective, randomised, arm crossover arm study conducted at 16 haemophilia treatment centres in Europe and the United States. It compared 6 months of FEIBA prophylaxis with 6 months of on-demand therapy in patients with severe haemophilia A with FVIII inhibitors.19 Learn more about the Pro-FEIBA Study.

The PROOF Study was a phase 3, prospective, randomised, open-label, parallel study conducted at 17 centres globally. Patients were 7 to 56 years of age, with haemophilia A or B with a history of inhibitors refractory to increased FVIII or FIX dosing for ≥ 12 months with ≥ 12 bleeding episodes in the 12 months prior to enrolment. Learn more about the PROOF Study

Early initiation of prophylaxis may help protect joints longer4, 7, 16, 19, 20

Early primary prophylaxis in children with inhibitors could provide benefits similar to those seen in children who receive primary factor VIII prophylaxis.7, 16, 19 The potential benefits are many, including4, 7, 19, 20:

  • Marked reduction in the frequency of bleeds
  • Prevention of severe arthropathy
  • Improvement or maintenance of range of motion

FEIBA is already approved in over 60 countries worldwide, and indicated in over 40 for prophylaxis19

Notations

ns=not significant.

References

  1. 1 World Federation of Hemophilia. Suggestions for the management of factor VIII inhibitors. 2000.
  2. 2 Tjønnfjord GE, Holme PA. Factor eight inhibitor bypass activity (FEIBA) in the management of bleeds in hemophilia patients with high-titer inhibitors. Vasc Health Risk Manag. 2007;3:527-531.
  3. 3 Valentino LA. The benefits of prophylactic treatment with APCC in patients with haemophilia and high-titre inhibitors: a retrospective case series. Haemophilia. 2009;15:733-742.
  4. 4 Leissinger CA, Becton DL, Ewing NP, et al. Prophylactic treatment with activated prothrombin complex concentrate (FEIBA) reduces the frequency of bleeding episodes in paediatric patients with haemophilia A and inhibitors. Haemophilia. 2007:1-7.
  5. 5 Roosendaal G, Lafeber F. Prophylactic treatment for prevention of joint disease in hemophilia - cost versus benefit. N Engl J Med. 2007;357:603-604.
  6. 6 Raffini L, Manno C. Modern management of haemophilic arthropathy. Br J Haematol. 2007;136:777-787.
  7. 7 Ettingshausen CE, Kreuz W. Early long-term FEIBA prophylaxis in haemophilia A patients with inhibitor after failing immune tolerance induction: A prospective clinical case series. Haemophilia. 2010;16:90-100.
  8. 8 Bossard D, Carrillon Y, Stieltjes N, et al. Management of haemophilicarthropathy. Haemophilia. 2008;14(suppl 4):11-19.
  9. 9 Valentino LA. Assessing the benefits of FEIBA prophylaxis in haemophilia patients with inhibitors. Haemophilia. 2010;16:263-271.
  10. 10 Perry D, Berntorp E, Tait C, et al. FEIBA prophylaxis in haemophilia patients: a clinical update and treatment recommendations. Haemophilia. 2010;16:80-89.
  11. 11 Valentino LA, Carcao M, Mathew P, et al. The application of bypassing agent prophylaxis in haemophilia A patients with inhibitors: a meeting report. Haemophilia. 2009;15:959-965.
  12. 12 World Federation of Hemophilia. Guidelines for the Management of Hemophilia. 2012.
  13. 13 Berntorp E, Boulyjenkov V, Brettler D, et al. Modern treatment of haemophilia. Bull World Health Organ. 1995;73:691-701.
  14. 14 US National Hemophilia Foundation. Medical and Scientific Advisory Council (MASAC) Recommendation Concerning Prophylaxis (Regular administration of clotting factor concentrate to prevent bleeding). MASAC Document #179. 2007.
  15. 15 Data on file. Baxter BioScience Corp; Westlake Village, Calif.
  16. 16 Antunes SV, Tangada S, Stasyshyn O, et al. Randomized comparison of prophylaxis and on-demand regimens with FEIBA NF in the treatment of haemophilia A and B with inhibitors [published online ahead of print August 1, 2013]. Haemophilia. 2014;20(1):65-72. DOI:10.1111/hae.12246.
  17. 17 Stasyshyn O, Antunes SV, Mamanov V, et al. Health-related quality of life in hemophilia patients with inhibitors receiving prophylaxis with anti-inhibitor coagulant complex (AICC): results from AICC Prophylaxis Study. Abstract presented at: XXIV Congress of the International Society on Thrombosis and Haemostasis; June 29–July 4, 2013; Amsterdam, the Netherlands.
  18. 18 Gringeri A, Leissinger C, Cortesi PA, et al. Health-related quality of life in patients with haemophilia and inhibitors on prophylaxis with anti-inhibitor complex concentrate: results from the Pro-FEIBA study. Haemophilia. 2013;19:736-743.
  19. 19 Leissinger C, Gringeri A, Antmen B, et al. Anti-Inhibitor Coagulant Complex Prophylaxis in Hemophilia with Inhibitors. N Engl J Med. 2011;365:1684-1692.
  20. 20 Kreuz AW, Manco-Johnson MJ, Gazengel C, et al. Recombinant FVIII formulated with sucrose (rFVIII-FS) is safe and efficacious in pediatric patients with hemophilia. Blood. 2000;96(11):266a.
  21. 21 Jimenez-Yuste V, Alvarez MT, Martin-Salces M, et al. Prophylaxis in 10 patients with severe haemophilia A and inhibitor: different approaches for different clinical situations. Haemophilia. 2009;15:203-209.
  22. 22 Arnold WD, Hilgartner MW. Hemophilic arthropathy: current concepts of pathogenesis and management. J Bone Joint Surg Am. 1977;59:287-305.
  23. 23 Löfqvist T, Nilsson IM, Berntorp E, et al. Haemophilia prophylaxis in young patients—a long-term follow-up. J Intern Med. 1997;241:395-400.
  24. 24 Madhok R, York J, Sturrock RD. Haemophilic arthritis. Ann Rheum Dis. 1991;50:588-591.
  25. 25 Hilgartner MW, Makipernaa A, DiMichele DM. Long-term FEIBA prophylaxis does not prevent progression of existing joint disease. Haemophilia. 2003;9;261-268.

Publications

Visit Haemophilia to read the PROOF Study and access to more articles related to managing haemophilia patients with inhibitors. Read more

Sustained activity

FEIBA offers a long dosing interval. Read more

Demonstrated efficacy in prophylaxis

Learn how FEIBA prophylaxis can reduce bleed frequency and preserve joints. Read more

Dosing FEIBA

Learn how to dose FEIBA. Read more

Prophylaxis in clinical practice

Learn why prophylaxis with bypassing therapy is increasingly used for haemophilia patients with inhibitors. Read more