595
Views
18
CrossRef citations to date
0
Altmetric
Review

Prophylactic versus on-demand treatments for hemophilia: advantages and drawbacks

&
Pages 567-576 | Received 22 Mar 2018, Accepted 06 Jun 2018, Published online: 19 Jun 2018

References

  • Bolton-Maggs PH, Pasi KJ. Haemophilias A and B. Lancet. 2003;361:1801–1809.
  • Jayandharan GR, Srivastava A. The phenotypic heterogeneity of severe hemophilia. Semin Thromb Hemost. 2008;34:128–142.
  • Pavlova A, Oldenburg J. Defining severity of hemophilia: more than factor levels. Semin Thromb Hemost. 2013;39:702–710.
  • White GCII, Rosendaal F, Aledort LM, et al. Factor VIII and Factor IX Subcommittee. 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.
  • Pollmann H, Richter H, Ringkamp H, et al. When are children diagnosed as having severe haemophilia and when do they start to bleed? A 10-year single-centre PUP study. Eur J Pediatr. 1999;158:S166–70.
  • Fischer K, Van Der Bom JG, Mauser-Bunschoten EP, et al. The effects of postponing prophylactic treatment on long-term outcome in patients with severe hemophilia. Blood. 2002;99:2337–2341.
  • Pergantou H, Matsinos G, Papadopoulos A, et al. Comparative study of validity of clinical, X-ray and magnetic resonance imaging scores in evaluation and management of haemophilicarthropathy in children. Haemophilia. 2006;12:241–247.
  • 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:e1-47.
  • Ahlberg A. Haemophilia in Sweden VII. Incidence, treatment and prophylaxis of arthropathy and other musculoskeletal manifestations of haemophilia A and B. Acta Orthop Scand. 1965;77:5–99.
  • Nilsson IM, Blomback M, Ahlberg A. Our experience in Sweden with prophylaxis on haemophilia A. Bibl Haematol. 1970;34:111–124.
  • Van Creveld S. Prophylaxis of joint hemorrhages in hemophilia. Acta Haematol. 1969;41:206–214.
  • 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.
  • Fischer K, Van Der Bom JG, Mauser-Bunschoten EP, et al. Changes in treatment strategies for severe haemophilia over the last 3 decades: effects on clotting factor consumption and arthropathy. Haemophilia. 2001;7:446–452.
  • 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.
  • Gringeri A, Lundin B, Von Mackensen S, et al. A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study).. J Thromb Haemost. 2011;9:700–710.
  • Clausen N, Petrini P, Claeyssens-Donadel S, et al. PedNet, Research of Determinants of Inhibitor development (RODIN) Study Group. Similar bleeding phenotype in young children with haemophilia A or B: a cohort study. Haemophilia. 2014;20:747–755.
  • Manco-Johnson MJ, Kempton CL, Reding MT, et al. Randomized, controlled, parallel-group trial of routine prophylaxis vs on-demand treatment with sucrose-formulated recombinant factor VIII in adults with severe hemophilia A (SPINART). J Thromb Haemost. 2013;11:1119–1127.
  • Khawaji M, Astermark J, Berntorp E. Lifelong prophylaxis in a large cohort of adult patients with severe haemophilia: a beneficial effect on orthopaedic outcome and quality of life. Eur J Haematol. 2012;88:329–335.
  • Aledort LM, Haschmeyer RH, Pettersson H. A longitudinal study of orthopaedic outcomes for severe factor-VIII-deficient haemophiliacs. The Orthopaedic Outcome Study Group. J Intern Med. 1994;236:391–399.
  • Blanchette VS, Key NS, Ljung LR, et al. Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost. 2014;12:1935–1939.
  • Fisher K, Astermark J, Van Der Bom JG, et al. Prophylactic treatment for severe haemophilia: comparison of an intermediate dose regimen to a high dose regimen. Haemophilia. 2002;8:753–760.
  • Feldman BM, Pai M, Rivard GE, et al. Association of Hemophilia Clinic Directors of Canada Prophylaxis Study Group, et al. Tailored prophylaxis in severe haemophilia A: interim results from the first 5 year of the Canadian Hemophilia Primary Prophylaxis Study. J Thromb Haemost. 2006;4:1228–1236.
  • Fischer K, Ljung R. Primary prophylaxis in haemophilia care: guideline update 2016. Blood Cells Mol Dis. 2017;67:81–85.
  • Collins PW, Blanchette VS, Fischer K, et al. rAHF–PFM Study Group. Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A. J Thromb Haemost. 2009;7:413–420.
  • Jimenez-Yuste V, Auerswald G, Benson G, et al. Achieving and maintaining an optimal through level for prophylaxis in haemophilia: the past, the present and the future. Blood Transfus. 2014;12:314–319.
  • Skinner MW. WFH: Closing the global gap – achieving optimal care. Haemophilia. 2012;18:S1–S12.
  • Liesner RJ, Vora AJ, Hann IM, et al. Use of central venous catheters in children with severe congenital coagulopathy. Br J Haematol. 1995;91:203–220.
  • Blanchette VS, Al-Musa A, Stain AM, et al. Central venous access devices in children with haemophilia. Blood Coag Fibrin. 1996;7:S39–S44.
  • Santagostino E, Gringeri A, Muça-Perja M, et al. A prospective clinical trial of implantable central venous access in children with haemophilia. Br J Haematol. 1998;102:1224–1228.
  • Langley AR, Stain AM, Chan A, et al. Experience with central venous access devices (CVADs) in the Canadian hemophilia primary prophylaxis study (CHPS). Haemophilia. 2015;21:469–476.
  • Khair K, Ranta S, Thomas A, et al. PedNet study group. The impact of clinical practice on the outcome of central venous access devices in children with haemophilia. Haemophilia. 2017;23:e276–81.
  • Hothi DK, Kelsall W, Baglin T, et al. Bacterial endocarditis in a child with haemophilia B: risks of central venous catheters. Haemophilia. 2001;7:507–510.
  • Journeycake JM, Quinn CT, Miller KL, et al. Catheter-related deep venous thrombosis in children with hemophilia. Blood. 2001;98:1727–1731.
  • Ettingshausen CE, Kurnik K, Schobess R, et al. Catheter-related thrombosis in children with hemophilia A: evidence of a multifactorial disease. Blood. 2002;99:1499–1500.
  • Santagostino E, Gringeri A, Berardinelli L, et al. Long-term safety and feasibility of arteriovenous fistulae as vascular accesses in children with haemophilia: a prospective study. Br J Haematol. 2003;123:502–506.
  • Hacker MR, Geraghty S, Manco-Johnson M. Barriers to compliance with prophylaxis therapy in haemophilia. Haemophilia. 2011;7:392–396.
  • Schrijvers LH, Uitslager N, Schuurmans MJ, et al. Barriers and motivators of adherence to prophylactic treatment in haemophilia: a systematic review. Haemophilia. 2013;19:355–361.
  • Meichenbaum D, Turk DC. Facilitating treatment adherence. New York: Plenum Press; 1987.
  • Duncan N, Kronenberger W, Roberson C, et al. VERITAS-Pro: a new measure of adherence to prophylactic regimens in haemophilia. Haemophilia. 2010;16:247–255.
  • Llewellyn CD, Miners AH, Lee CA, et al. The illness perceptions and treatment beliefs of individuals with severe haemophilia and their role in adherence to home treatment. Psycho Healh. 2003;18:185–200.
  • De Moerloose P, Urbancik W, Van Den Berg HM, et al. A survey of adherence to haemophilia therapy in six European countries: results and recommendations. Haemophilia. 2008;14:931–938.
  • Ho S, Gue D, McIntosh K, et al. An objective method for assessing adherence to prophylaxis in adults with severe haemophilia. Haemophilia. 2014;20:39–43.
  • Schrijvers LH, Kars MC, Beijlevelt Van Der Zande M, et al. Unravelling adherence to prophylaxis in haemophilia: a patients’ perspective. Haemophilia. 2015;21:612–621.
  • Verma SP, Dutta TK, Mahadevan S, et al. A randomized study of very low-dose factor VIII prophylaxis in severe haemophilia – a success story from a resource limited country. Haemophilia. 2016;22:342–348.
  • Gouider E, Jouini L, Achour M, et al. Low dose prophylaxis in Tunisian children with haemophilia. Heamophilia. 2017;23:77–81.
  • Collins PW. Personalized prophylaxis in haemophilia patients. Haemophilia. 2012;18:S131–5.
  • Farrugia A, Noone D, Schlenkrich U, et al. Issues in assessing products for the treatment of hemophilia – the intersection between efficacy, economics, and ethics. J Blood Med. 2015;6:185–195.
  • Morfini M, Haya S, Tagariello G, et al. European study on orthopaedic status of haemophilia patients with inhibitors. Haemophilia. 2007;13:606–612.
  • 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;102:2358–2363.
  • Dolan G, Benson G, Duffy A, et al. Haemophilia B: where are we now and what does the future hold?. Blood Rev. 2018;32(1):52–60.
  • Astermark J, Altisent C, Batorova A, et al. European Haemophilia Therapy Standardisation Board. Non-genetic risk factors and the development of inhibitors in haemophilia: a comprehensive review and consensus report. Haemophilia. 2010;16:747–766.
  • Santagostino E, Mancuso ME, Rocino A, et al. Environmental risk factors for inhibitor development in children with haemophilia A: a case–control study. Br J Haematol. 2005;130:422–427.
  • Gouw SC, Van Der Bom JG, Van Den Berg MH. Treatment-related risk factors of inhibitor development in previously untreated patients with hemophilia A: the CANAL cohort study. Blood. 2007;109:4648–4654.
  • Kurnik K, Auerswald G, Kreuz W. Inhibitors and prophylaxis in paediatrichaemophilia patients: focus on the German experience. Thromb Res. 2014;134:S27–32.
  • Gouw SC, Van Den Berg HM, Fischer K, et al. PedNet, Research Of Determinants of INhibitor development (RODIN) StudyGroup, et al. Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study. Blood. 2013;121:4046–4055.
  • Astermark J. Inhibitor development: patient-determined risk factors. Haemophilia. 2009;16:66–70.
  • Peyvandi F, Mannucci PM, Garagiola I, et al. A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A. N Engl J Med. 2016;374:2054–2064.
  • Young G, Shafer FE, Rojas P, et al. Single 270 micro kg(−1)-dose rFVIIa vs. Standard 90 micro kg(−1)-dose rFVIIa and aPCC for home treatment of joint bleeds in haemophilia patients with inhibitors: a randomized comparison. Haemophilia. 2008;14:287–294.
  • Astermark J, Donfield SM, DiMichele DM, et al. FENOC Study Group. A randomized comparison of bypassing agents in haemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study. Blood. 2007;109:546–551.
  • Oldenburg J, Austin SK, Kessler CM. ITI choice for the optimal management of inhibitor patients – from a clinical and farmacoeconomic perspective. Haemophilia. 2014;20:S17–26.
  • DiMichele D. The North American Immune Tolerance Registry: contributions to the thirty-year experience with immune tolerance therapy. Haemophilia. 2009;15:320–328.
  • 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.
  • 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. Haemophilia. 2014;20:65–72.
  • Konkle BA, Ebbesen LS, Erhardtsen E, et al. Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in hemophilia patients with inhibitors. J Thromb Haemost. 2007;5:1904–1913.
  • Ljung R. Aspects of prophylactic treatment of hemophilia. Thromb J. 2016;14:S60–63.
  • Laffan M. New products for treatment of haemophilia. Br J Haematol. 2016;172:23–31 .
  • Ober RJ, Martinez C, Lai X, et al. Exocytosis of IgG as mediated by the receptor, FcRn: an analysis at a single- molecule level. Proc Natl Acad Sci USA. 2004;101:11076–11081.
  • Mahlangu J, Powell JS, Ragni MV, et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood. 2014;123:317–325.
  • Nolan B, Mahlangu J, Perry D, et al. Long-term safety and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in subjects with haemophilia A. Haemophilia. 2016;22:72–80.
  • Young G, Mahlangu J, Kulkarni R, et al. Recombinant factor VIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A. J Thromb Haemost. 2015;13:967–977.
  • Shapiro AD, Ragni MV, Valentino LA, et al. Recombinant fusion IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients. Blood. 2012;119:666–672.
  • Powell JS, Pasi KJ, Ragni MV, et al. Phase 3 study of recombinant factor IXFc fusion protein in hemophilia B. N Engl J Med. 2013;369:2313–2323.
  • Fischer K, Kulkarni R, Nolan B, et al. Recombinant factor IXFc fusion protein in children with hemophilia B (Kids B-Long): results from a multicentre, non-randomised phase 3 study. Lancet Haematol. 2017;4:e75–e82.
  • Pasi KJ, Fisher K, Ragni M, et al. Long-term safety and efficacy of extended-interval prophylaxis with recombinant factor IXFc fusion protein (rFIXFc)in subjects with hemophilia B. Thromb Haemost. 2017;117:508–518.
  • Konkle BA, Stasyshyn O, Chowdary P, et al. Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A. Blood. 2015 27;126:1078–1085.
  • Reding MT, Ng HJ, Poulsen LH, et al. Safety and Efficacy of BAY 94-9027, a prolonged-half-life factor VIII. J Thromb Haemost. 2017;15:411–419.
  • Giangrande P, Andreeva T, Chowdary P, et al. Clinical evaluation of glycoPEGylated recombinant FVIII: Efficacy and safety in severe haemophilia A. Thromb Haemost. 2017;117:252–261.
  • Ostergaard H, Bjelke JR, Hansen L, et al. Prolonged half-life and preserved enzymatic properties of factor IX selectively PEGylated in native N-glycans in the activation peptide. Blood. 2011;118:2333–2341.
  • Negrier C, Knobe K, Tiede A, et al. Enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX: a first human dose trial in patients with hemophilia B. Blood. 2011;118:2695–2701.
  • Young G, Collins PW, Colberg T, et al. Nonacog beta pegol (N9-GP) in haemophilia B: a multinational phase III safety and efficacy extension trial (paradigm 4). Thromb Res. 2016;141:69–76.
  • Carcao M, Zak M, Karim FA, et al. Nonacog beta pegol in previously treated children with hemophilia B: results from an international open-label phase 3 trial. J Thromb Haemost. 2016;14:1521–1529.
  • Metzner HJ, Weimer T, Kronthaler U, et al. Genetic fusion to albumin improves the pharmacokinetic properties of factor IX. Thromb Haemost. 2009;102:634–644.
  • Santagostino E, Negrier C, Klamroth R, et al. Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients. Blood. 2012;120:2405–2411.
  • Martinowitz U, Lissitchkov T, Lubetsky A, et al. Results of a phase I/II open-label, safety and efficacy trial of coagulation factor IX (recombinant), albumin fusion protein in haemophilia B patients. Haemophilia. 2015;21:784–790.
  • Santagostino E, Martinowitz U, Lissitchkov T, et al. Long acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial. Blood. 2016;127:1761–1769.
  • Kenet G, Chambost H, Male C, et al. Long-acting recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in children: results of a phase 3 trial. Thromb Haemost. 2016;116:659–688.
  • Bjorkman S, Folkesson A, Jonsson S. Pharmacokinetics and dose requirements of factor VIII over the age range 3-74 years: a population analysis based on 50 patients with long-term prophylactic treatment for haemophilia A. Eur J Clin Pharmacol. 2009;65:989–998.
  • Bjorkman S, Shapiro AD, Berntorp E. Pharmacokinetics of recombinant factor IX in relation to age of patient: implications for dosing in prophylaxis. Haemophilia. 2001;7:133–139.
  • Peyvandi F, Garagiola I, Biguzzi E. Advances in the treatment of bleeding disorders. J Thromb Haemost. 2016;14:2095–2106 .
  • Shima M, Hanabusa H, Taki M, et al. Factor VIII-mimetic function of humanized bispecific antibody in hemophilia A. N Engl J Med. 2016;374:2044–2053.
  • Uchida N, Sambe T, Yoneyama K, et al. A first-in-human phase 1 study of ACE910, a novel factor VIII-mimetic bispecific antibody, in health subjects. Blood. 2016;127:1633–1641.
  • Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia with inhibitors. N Engl J Med. 2017;377:809–818 .
  • Mast AE. Tissue factor pathway inhibitor: multiple anticoagulant activities for a single protein. Arterioscler Thromb Vasc Biol. 2016;36:9–14.
  • Erhardtsen E, Ezban M, Madsen MT, et al. Blocking of tissue factor pathway inhibitor (TFPI) shortens the bleeding time in rabbits with antibody induced haemophilia A. Blood Coagul Fibrinolysis. 1995;6:388–394.
  • Prasad S, Lillicrap D, Labelle A, et al. Efficacy and safety of a new-class hemostatic drug candidate, AV513, in dogs with hemophilia A. Blood. 2008;111:672–679.
  • Maroney SA, Mast AE. New insights into the biology of tissue factor pathway inhibitor. J Thromb Haemost. 2015;13:S200–7.
  • Petersen LC. Hemostatic properties of a TFPI antibody. Thromb Res. 2012;129(Suppl2):44–45.
  • Chowdary P, Lethagen S, Friederich U, et al. Safety and pharmacokinetics of anti-TFPIantibody (concizumab) in healthy volunteers and patients with hemophilia A: a randomized first human dose trial. J Thromb Haemost. 2015;13:743–754.
  • Gu J-M, Zhao X-Y, Schwarz T, et al. Mechanistic modeling of the pharmacodynamic and pharmacokinetic relationship of tissue factor pathway inhibitor-neutralizing antibody (BAY 1093884) in cynomolgus monkeys. AAPS J. 2017;19:1186–1195.
  • Cardinal M, Kantaridis C, Zhu T et al. A first-in-human (FIH) study of the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of PF-06741086, an anti-TFPI monoclonal antibody, following administration of single subcutaneous or intravenous doses in healthy adult male volunteers. ISTH Congress 2017 Jul 8- 13;Berlin, Germany
  • Bolliger D, Szlam F, Suzuki N, et al. Heterozygous antithrombin deficiency improves in vivo haemostasis in FVIII-deficient mice. Thromb Haemost. 2010;103:1233–1238.
  • Ragni MV. Targeting antithrombin to treat hemophilia. N Engl J Med. 2015;373:389–391.
  • Pasi KJ, Rangarajan S, Georgiev P, et al. Targeting of antithrombin in hemophilia A or B with RNAitherapy. N Engl J Med. 2017;377:819–828.
  • Pasi KJ, Georgiev P, Mant T, et al. A subcutaneously administered investigational RNAi therapeutic (ALN-AT3) targeting antithrombin for treatment of hemophilia: interim weekly and monthly dosing results in patients with hemophilia A or B. Blood. 2015;126:551.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.