Haemophilia B: impact on patients and economic burden of disease

 

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Summary

Worldwide, haemophilia is the most common hereditary bleeding disorder. The incidence of haemophilia B, however, is considerably less than haemophilia A and consequently appears to have received less attention in the research literature. This article aims to summarise the available evidence documenting the patient and economic burden associated with haemophilia B and current methods of disease management. Both the immediate and long-term clinical consequences of haemophilia B can have significant implications for patients in terms of functional limitations and diminished health-related quality of life (HRQOL). Evidence demonstrates that primary prophylaxis is the optimal strategy for replacing missing clotting factor IX (FIX) and managing haemophilia B. Use of recombinant FIX (rFIX) over plasma-derived FIX (pd-FIX) is also generally preferred for safety reasons. Prophylaxis using currently available rFIX products, however, requires a demanding regimen of intravenous infusions 2–3 times a week which may have significant implications for adherence and ultimately the long-term efficacy of such regimens. Only limited assessments of the cost-effectiveness of prophylactic versus on-demand FIX treatment regimens have been conducted to date. Prophylaxis, however, is generally more costly as greater quantities of FIX are consumed. Any reduction in FIX replacement dosing frequency is expected to improve patient adherence and contribute to improved clinical outcomes, further supporting the costeffectiveness of such interventions. Although a rare disease, as economic constraints for healthcare increase, generating further information regarding the key clinical, patient and economic outcomes associated with haemophilia B will be essential for supporting improvements in care for people with haemophilia B.

• References

• 1 Bowen DJ. Haemophilia A and haemophilia B: molecular insights. J Clin Pathol: Mol Pathol 2002; 55: 1-18.
  CrossrefPubMedGoogle Scholar
• 2 Skinner MW. Treatment for all: a vision for the future. Haemophilia 2006; 12 (Suppl. 03) 169-173.
  PubMedGoogle Scholar
• 3 Bolton-Maggs PH, Pasi KJ, Haemophilias A, Lancet B. 2003; 361: 1801-1809.
  PubMed
• 4 Aledort LM. Optimizing the treatment of haemophilia B: laboratory and clinical perspectives. Haemophilia 2010; 16 (Suppl. 06) 1-2.
  PubMedGoogle Scholar
• 5 Cavendish Marshall. Diseases and disorders (volume 2).. New York: Marshall Cavendish; 2008
• 6 Sherry DD. Avoiding the impact of musculoskeletal pain on quality of life in children with hemophilia. Orthop Nurs 2008; 27: 103-108.
  CrossrefPubMedGoogle Scholar
• 7 Janco RL, Maclean WE, Perrin JM, Gortmaker SL. A prospective study of patterns of bleeding in boys with haemophilia. Haemophilia 1996; 2: 202-206.
  CrossrefPubMedGoogle Scholar
• 8 White GC, Rosendaal F, Aledort LM. et al. Definitions in hemophilia. Recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 2001; 85: 560.
  Article in Thieme ConnectPubMedGoogle Scholar
• 9 Aznar JA, Lucia F, Abad-Franch L. et al. Haemophilia in Spain. Haemophilia 2009; 15: 665-675.
  CrossrefPubMedGoogle Scholar
• 10 Katz J. Prevalence of factor IX inhibitors among patients with haemophilia B: results of a large-scale North American survey. Haemophilia 1996; 2: 28-31.
  CrossrefPubMedGoogle Scholar
• 11 Nerich V, Tissot E, Faradji A. et al. Cost-of-illness study of severe haemophilia A and B in five French haemophilia treatment centres. Pharm World Sci 2008; 30: 287-292.
  CrossrefPubMedGoogle Scholar
• 12 Makris M. Is VIII worse than IX?. Blood 2009; 114: 750-751.
  CrossrefPubMedGoogle Scholar
• 13 Lowe GD, Ludlam CA. Less severe bleeding in hemophilia B than in hemophilia A. J Thromb Haemost 2008; 6: 1982-1983.
  CrossrefPubMedGoogle Scholar
• 14 Tagariello G, Iorio A, Santagostino E. et al. Comparison of the rates of joint arthroplasty in patients with severe factor VIII and IX deficiency: an index of different clinical severity of the 2 coagulation disorders. Blood 2009; 114: 779-784.
  CrossrefPubMedGoogle Scholar
• 15 Santagostino E. Prophylaxis in haemophilia B patients: unresolved issues and pharmacoeconomic implications. Haemophilia 2010; 16 (Suppl. 06) 13-17.
  PubMedGoogle Scholar
• 16 von Mackensen S. Quality of life and sports activities in patients with haemophilia. Haemophilia 2007; 13 (Suppl. 02) 38-43.
  PubMedGoogle Scholar
• 17 Plug I, Peters M, Mauser-Bunschoten EP. et al. Social participation of patients with hemophilia in the Netherlands. Blood 2008; 111: 1811-1815.
  CrossrefPubMedGoogle Scholar
• 18 Ghanizadeh A, Baligh-Jahromi P. Depression, anxiety and suicidal behaviour in children and adolescents with Haemophilia. Haemophilia 2009; 15: 528-532.
  CrossrefPubMedGoogle Scholar
• 19 Miners AH, Sabin CA, Tolley KH. et al. Assessing health-related quality-of-life in individuals with haemophilia. Haemophilia 1999; 5: 378-385.
  CrossrefPubMedGoogle Scholar
• 20 Aznar JA, Magallon M, Querol F. et al. The orthopaedic status of severe haemophiliacs in Spain. Haemophilia 2000; 6: 170-176.
  CrossrefPubMedGoogle Scholar
• 21 Molho P, Rolland N, Lebrun T. et al. Epidemiological survey of the orthopaedic status of severe haemophilia A and B patients in France. The French Study Group. Haemophilia 2000; 6: 23-32.
  CrossrefPubMedGoogle Scholar
• 22 Fischer K, Bom JG, Mauser-Bunschoten EP. et al. Effects of haemophilic arthropathy on health-related quality of life and socio-economic parameters. Haemophilia 2005; 11: 43-48.
  CrossrefPubMedGoogle Scholar
• 23 Ware JE, Jr. Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30: 473-483.
  CrossrefPubMedGoogle Scholar
• 24 Brooks R. EuroQol: the current state of play. Health Policy 1996; 37: 53-72.
  CrossrefPubMedGoogle Scholar
• 25 Landgraf JM, Abetz LN. The physical and psychosocial well-being of children representing three cultural groups: Initial self-reports using the Child Health Questionnaire (CHQ-CF87). Psychology, and Health, Quality of Life: Recent Advances in Theory and Methods 1997; 12: 839-854.
  PubMedGoogle Scholar
• 26 Remor E, Young NL, von Mackensen S. et al. Disease-specific quality-of-life measurement tools for haemophilia patients. Haemophilia 2004; 10 (Suppl. 04) 30-34.
  PubMedGoogle Scholar
• 27 Young NL, Bradley CS, Wakefield CD. et al. How well does the Canadian Haemophilia Outcomes-Kids’ Life Assessment Tool (CHO-KLAT) measure the quality of life of boys with haemophilia?. Pediatr Blood Cancer 2006; 47: 305-311.
  CrossrefPubMedGoogle Scholar
• 28 Poonnoose PM, Srivastava A. Functional assessment of arthropathy--an international perspective. Semin Hematol 2006; 43: S27-S32.
  PubMedGoogle Scholar
• 29 Poonnoose PM, Thomas R, Keshava SN. et al. Psychometric analysis of the Functional Independence Score in Haemophilia (FISH). Haemophilia 2007; 13: 620-626.
  CrossrefPubMedGoogle Scholar
• 30 Bullinger M, von Mackensen S, Fischer K. et al. Pilot testing of the ‘Haemo-QoL’ quality of life questionnaire for haemophiliac children in six European countries. Haemophilia 2002; 8 (Suppl. 02) 47-54.
  CrossrefPubMedGoogle Scholar
• 31 von Mackensen S, Bullinger M. Development and testing of an instrument to assess the Quality of Life of Children with Haemophilia in Europe (Haemo-QoL). Haemophilia 2004; 10 (Suppl. 01) 17-25.
  PubMedGoogle Scholar
• 32 von Mackensen S, Gringeri A. Quality of Life in Hemophilia. Handbook of Disease Burdens and Quality of Life Measures.. Heidelberg: Springer; 2009: 1895-1920.
  Google Scholar
• 33 van Genderen FR, van Meeteren NL, Van Der Bom JG. et al. Functional consequences of haemophilia in adults: the development of the Haemophilia Activities List. Haemophilia 2004; 10: 565-571.
  CrossrefPubMedGoogle Scholar
• 34 van Genderen FR, Westers P, Heijnen L. et al. Measuring patients’ perceptions on their functional abilities: validation of the Haemophilia Activities List. Haemophilia 2006; 12: 36-46.
  PubMedGoogle Scholar
• 35 Arranz P, Remor E, Quintana M. et al. Development of a new disease-specific quality-of-life questionnaire to adults living with haemophilia. Haemophilia 2004; 10: 376-382.
  CrossrefPubMedGoogle Scholar
• 36 Remor E, Arranz P, Quintana M. et al. Psychometric field study of the new haemophilia quality of life questionnaire for adults: the ‘Hemofilia-QoL’. Haemophilia 2005; 11: 603-610.
  CrossrefPubMedGoogle Scholar
• 37 Remor E. Desarrollo de una Medida Específica para la Evaluación de la Calidad de Vida en Pacientes Adultos Viviendo con Hemofilia en América-Latina: el Hemolatin-QoL. Revista Interamericana de Psicología 2005; 39: 211-220.
  PubMedGoogle Scholar
• 38 von Mackensen S, Strandberg-Larsen M, Celerier S. Linguistic validation of haemophilia-specific patient-rated outcomes (Haemo-QoL, Haem-A-QoL, Hemo-Sat) in up to 32 languages. Value in Health 2009; 12: A383.
  PubMedGoogle Scholar
• 39 Darby SC, Ewart DW, Giangrande PL. et al. Mortality before and after HIV infection in the complete UK population of haemophiliacs. UK Haemophilia Centre Directors’ Organisation. Nature 1995; 377: 79-82.
  CrossrefPubMedGoogle Scholar
• 40 Darby SC, Kan SW, Spooner RJ. et al. Mortality rates, life expectancy, and causes of death in people with hemophilia A or B in the United Kingdom who were not infected with HIV. Blood 2007; 110: 815-825.
  CrossrefPubMedGoogle Scholar
• 41 Ludlam CA, Turner ML. Managing the risk of transmission of variant Creutzfeldt Jakob disease by blood products. Br J Haematol 2006; 132: 13-24.
  CrossrefPubMedGoogle Scholar
• 42 Ungchusak K, Auewarakul P, Dowell SF. et al. Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med 2005; 352: 333-340.
  CrossrefPubMedGoogle Scholar
• 43 UKHCDO (United Kingdom Haemophilia Centre Doctors’ Organisation). Guidelines on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders. Haemophilia 2003; 9: 1-23.
  PubMedGoogle Scholar
• 44 Celis P, Silvester G. European Regulatory guidance on virus safety of recombinant proteins, monoclonal antibodies and plasma derived medicinal products. Dev Biol (Basel) 2004; 118: 3-10.
  PubMedGoogle Scholar
• 45 Batlle J, Villar A, Liras A. et al. Consensus opinion for the selection and use of therapeutic products for the treatment of haemophilia in Spain. Blood Coagul Fibrinolysis 2008; 19: 333-340.
  CrossrefPubMedGoogle Scholar
• 46 MASAC recommendations concerning thetreatment of hemophilia and other bleeding disorders, revised October 2006 (Document #177).. National Hemophilia Foundation.;
• 47 Hemophilia and von Willebrand’s disease. 2. Management. Association of Hemophilia Clinic Directors of Canada. CMAJ 1995; 153: 147-157.
  PubMedGoogle Scholar
• 48 Gringeri A, Mantovani L, Mackensen SV. Quality of life assessment in clinical practice in haemophilia treatment. Haemophilia 2006; 12 (Suppl. 03) 22-29.
  CrossrefPubMedGoogle Scholar
• 49 Khair K. Children’s preferences of transfer devices for reconstitution of factors VIII and IX for the treatment of haemophilia. Haemophilia 2009; 15: 159-167.
  CrossrefPubMedGoogle Scholar
• 50 Lindvall K, Colstrup L, Wollter IM. et al. Compliance with treatment and understanding of own disease in patients with severe and moderate haemophilia. Haemophilia 2006; 12: 47-51.
  CrossrefPubMedGoogle Scholar
• 51 Tagariello G. Use of factor IX concentrates in active teenagers with hemophilia B. Blood Coagul Fibrinolysis 2004; 15 (Suppl. 02) S9-S10.
  CrossrefPubMedGoogle Scholar
• 52 Teitel JM, Barnard D, Israels S, Lillicrap D, Poon MC, Sek J. Home management of haemophilia. Haemophilia 2004; 10: 118-133.
  CrossrefPubMedGoogle Scholar
• 53 Kreuz W, Escuriola-Ettingshausen C, Funk M. et al. When should prophylactic treatment in patients with haemophilia A and B start?--The German experience. Haemophilia 1998; 4: 413-417.
  CrossrefPubMedGoogle Scholar
• 54 Lofqvist T, Nilsson IM, Berntorp E. et al. Haemophilia prophylaxis in young patients--a long-term follow-up. J Intern Med 1997; 241: 395-400.
  CrossrefPubMedGoogle Scholar
• 55 Monahan PE, Liesner R, Sullivan ST. et al. Safety and efficacy of investigator-prescribed BeneFIX prophylaxis in children less than 6 years of age with severe haemophilia B. Haemophilia 2010; 16: 460-468.
  PubMedGoogle Scholar
• 56 Nilsson IM, Berntorp E, Lofqvist T. et al. Twenty-five years’ experience of prophylactic treatment in severe haemophilia A and B. J Intern Med 1992; 232: 25-32.
  CrossrefPubMedGoogle Scholar
• 57 Coppola A, Franchini M, Tagliaferri A. Prophylaxis in people with haemophilia. Thromb Haemost 2009; 101: 674-681.
  Article in Thieme ConnectPubMedGoogle Scholar
• 58 Gringeri A. Long-term aspects of hemophilia B treatment: part II. Blood Coagul Fibrinolysis 2004; 15 (Suppl. 02) S15-S16.
  CrossrefPubMedGoogle Scholar
• 59 Ljung R. Prophylactic therapy in haemophilia. Blood Rev 2009; 23: 267-274.
  CrossrefPubMedGoogle Scholar
• 60 Manco-Johnson MJ, Abshire TC, Shapiro AD. et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 2007; 357: 535-544.
  CrossrefPubMedGoogle Scholar
• 61 Manco-Johnson MJ. Update on treatment regimens: prophylaxis versus on-demand therapy. Semin Hematol 2003; 40: 3-9.
  PubMedGoogle Scholar
• 62 Ettingshausen CE, Kreuz W. Long-term aspects of hemophilia B treatment: part I-role for prophylaxis. Blood Coagul Fibrinolysis 2004; 15 (Suppl. 02) S11-S13.
  PubMedGoogle Scholar
• 63 Khoriaty R, Taher A, Inati A. et al. A comparison between prophylaxis and on demand treatment for severe haemophilia. Clin Lab Haematol 2005; 27: 320-323.
  CrossrefPubMedGoogle Scholar
• 64 Tagliaferri A, Di Perna C, Rivolta GF. Secondary prophylaxis in adolescent and adult haemophiliacs. Blood Transfus 2008; 6 (Suppl. 02) s17-s20.
  PubMedGoogle Scholar
• 65 Tagliaferri A, Franchini M, Coppola A. et al. Effects of secondary prophylaxis started in adolescent and adult haemophiliacs. Haemophilia 2008; 14: 945-951.
  CrossrefPubMedGoogle Scholar
• 66 Royal S, Schramm W, Berntorp E. et al. Quality-of-life differences between prophylactic and on-demand factor replacement therapy in European haemophilia patients. Haemophilia 2002; 8: 44-50.
  CrossrefPubMedGoogle Scholar
• 67 Szucs TD, Offner A, Kroner B. et al. Resource utilisation in haemophiliacs treated in Europe: results from the European Study on Socioeconomic Aspects of Haemophilia Care. The European Socioeconomic Study Group. Haemophilia 1998; 4: 498-501.
  CrossrefPubMedGoogle Scholar
• 68 Mantovani LG, Monzini MS, Mannucci PM. et al. Differences between patients’, physicians’ and pharmacists’ preferences for treatment products in haemophilia: a discrete choice experiment. Haemophilia 2005; 11: 589-597.
  CrossrefPubMedGoogle Scholar
• 69 Naraine VS, Risebrough NA, Oh P. et al. Health-related quality-of-life treatments for severe haemophilia: utility measurements using the Standard Gamble technique. Haemophilia 2002; 8: 112-120.
  CrossrefPubMedGoogle Scholar
• 70 Roth DA, Kessler CM, Pasi KJ. et al. Human recombinant factor IX: safety and efficacy studies in hemophilia B patients previously treated with plasma-derived factor IX concentrates. Blood 2001; 98: 3600-3606.
  CrossrefPubMedGoogle Scholar
• 71 Shapiro AD, Di Paola J, Cohen A. et al. The safety and efficacy of recombinant human blood coagulation factor IX in previously untreated patients with severe or moderately severe hemophilia B. Blood 2005; 105: 518-525.
  CrossrefPubMedGoogle Scholar
• 72 Fischer K, Van Der Bom JG, Prejs R. et al. Discontinuation of prophylactic therapy in severe haemophilia: incidence and effects on outcome. Haemophilia 2001; 7: 544-550.
  CrossrefPubMedGoogle Scholar
• 73 Hacker MR, Geraghty S, Manco-Johnson M. Barriers to compliance with prophylaxis therapy in haemophilia. Haemophilia 2001; 7: 392-396.
  CrossrefPubMedGoogle Scholar
• 74 Schulte S. Half-life extension through albumin fusion technologies. Thromb Res 2009; 124 (Suppl. 02) S6-S8.
  CrossrefPubMedGoogle Scholar
• 75 Oldenburg J, Dolan G, Lemm G. Haemophilia care then, now and in the future. Haemophilia 2009; 15 (Suppl. 01) 2-7. 2-7.
  CrossrefPubMedGoogle Scholar
• 76 Escobar MA. Health economics in haemophilia: a review from the clinician’s perspective. Haemophilia 2010; 16 (Suppl. 03) 29-34.
  PubMedGoogle Scholar
• 77 Schramm W, Berger K. Economics of prophylactic treatment. Haemophilia 2003; 9 (Suppl. 01) 111-115.
  CrossrefPubMedGoogle Scholar
• 78 Smith PS, Teutsch SM, Shaffer PA. et al. Episodic versus prophylactic infusions for hemophilia A: a cost-effectiveness analysis. J Pediatr 1996; 129: 424-431.
  CrossrefPubMedGoogle Scholar
• 79 Evatt B. Economic Issues and Program Development for Hemophilia.. 2002. Seville: World Federation of Haemophilia Congress.;
• 80 Lippert B, Berger K, Berntorp E. et al. Cost effectiveness of haemophilia treatment: a cross-national assessment. Blood Coagul Fibrinolysis 2005; 16: 477-485.
  CrossrefPubMedGoogle Scholar
• 81 Kisker CT, Eisberg A, Schwartz B. the Mononine study group. Prophylaxis in factor IX deficiency product and patient variation. Haemophilia 2003; 9: 279-284.
  CrossrefPubMedGoogle Scholar
• 82 Ewenstein BM, Joist JH, Shapiro AD. et al. Pharmacokinetic analysis of plasma-derived and recombinant F IX concentrates in previously treated patients with moderate or severe hemophilia B. Transfusion 2002; 42: 190-197.
  CrossrefPubMedGoogle Scholar
• 83 White GC, Beebe A, Nielsen B. Recombinant factor IX. Thromb Haemost 1997; 78: 261-265.
  Article in Thieme ConnectPubMedGoogle Scholar
• 84 Poon MC, Lillicrap D, Hensman C. et al. Recombinant factor IX recovery and inhibitor safety: a Canadian post-licensure surveillance study. Thromb Haemost 2002; 87: 431-435.
  Article in Thieme ConnectPubMedGoogle Scholar
• 85 White GC, Shapiro AD, Kurczynski EM. et al. Variability of in vivo recovery of factor IX after infusion of monoclonal antibody purified factor IX concentrates in patients with hemophilia B. The Mononine Study Group. Thromb Haemost 1995; 73: 779-784.
  Article in Thieme ConnectPubMedGoogle Scholar
• 86 DiMichele D. Inhibitor development in haemphilia B: an orphan disease in need of attention. Br J Haematol 2007; 138: 315.
  PubMedGoogle Scholar
• 87 Scharrer I, Bray GL, Neutzling O. Incidence of inhibitors in haemophilia A patients--a review of recent studies of recombinant and plasma-derived factor VIII concentrates. Haemophilia 1999; 5: 145-154.
  CrossrefPubMedGoogle Scholar
• 88 Odeyemi IAO, Guest JF. Modelling the economic impact of recombinant activated factor VII compared ot activated prothrombin-complex concentrate in the home 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. Journal of Medical Economics 2002; 5: 119-133.
  CrossrefPubMedGoogle Scholar
• 89 Odeyemi IAO, Dano AM. Optimising immune tolerance induction strategies in the management of haemophilia patients with inhibitors: a cost-minimisation analysis. Curr Med Res Opinion 2009; 25: 239-250.
  CrossrefPubMedGoogle Scholar
• 90 Tencer T, Friedman HS, Li-McLeod J. et al. Medical costs and resource utilization for hemophilia patients with and without HIV or HCV infection. J Manag Care Pharm 2007; 13: 790-798.
  PubMedGoogle Scholar
• 91 Hoots WK, Nugent DJ. Evidence for the benefits of prophylaxis in the management of hemophilia A. Thromb Haemost 2006; 96: 433-440.
  Article in Thieme ConnectPubMedGoogle Scholar
• 92 Weinstein MC, Stason WB. Foundations of cost-effectiveness analysis for health and medical practices. N Engl J Med 1977; 296: 716-721.
  CrossrefPubMedGoogle Scholar
• 93 Miners AH, Sabin CA, Tolley KH. et al. Cost-utility analysis of primary prophylaxis versus treatment on-demand for individuals with severe haemophilia. Pharmacoeconomics 2002; 20: 759-774.
  CrossrefPubMedGoogle Scholar
• 94 O’Mahony B, Noone D, Tolley KH. An Introduction to Key Concepts in Health Economics for Hemophilia Organizations. 2010 World Federation of Haemophilia. Abstract 20–8–0010.
  PubMedGoogle Scholar
• 95 Wiedebusch S, Pollmann H, Siegmund B. et al. Quality of life, psychosocial strains and coping in parents of children with haemophilia. Haemophilia 2008; 14: 1014-1022.
  CrossrefPubMedGoogle Scholar
• 96 Ragni MV. Aging in haemophilia: getting to the heart of the matter. Thromb Haemost 2011; 105: 207-208.
  Article in Thieme ConnectPubMedGoogle Scholar