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Review article

Treatment Options in Hemophilia

Dtsch Arztebl Int 2019; 116: 791-8. DOI: 10.3238/arztebl.2019.0791

Miesbach, W; Schwäble, J; Müller, M M; Seifried, E

1.Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al.: Guidelines for the management of hemophilia. Haemophilia 2013; 19: e1–47 CrossRef MEDLINE
2.Wight J, Paisley S: The epidemiology of inhibitors in haemophilia A: a systematic review. Haemophilia 2003; 9: 418–35 CrossRef MEDLINE
3.Brackmann HH, Oldenburg J, Schwaab R: Immune tolerance for the treatment of factor VIII inhibitors—twenty years‘ ‚bonn protocol‘. Vox Sang 1996; 70 (Suppl 1): 30–5 CrossRef MEDLINE
4.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: 2054–64 CrossRef MEDLINE
5.Giangrande PLF, Hermans C, O‘Mahony B, et al.: European Haemophilia Consortium (EHC) and the European Association for Haemophilia and Allied Disorders (EAHAD).European principles of inhibitor management in patients with haemophilia. Orphanet J Rare Dis 2018; 13: 66 CrossRef MEDLINE PubMed Central
6.Fischer K, Hermans C, European Haemophilia Therapy Standardisation Board: the European principles of haemophilia care: a pilot investigation of adherence to the principles in Europe. Haemophilia 2013; 19: 35–43 CrossRef MEDLINE
7.Vorstand der Bundesärztekammer auf Empfehlung des Wissenschaftlichen Beirats: Querschnitts-Leitlinien (BÄK) zur Therapie mit Blutkomponenten und Plasmaderivaten. 4th edition 2014. www.bundesaerztekammer.de/fileadmin/user_upload/downloads/QLL_Haemotherapie_2014.pdf (last accessed on 10 September 2019).
8.Eichler H, Pedroni MA, Halimeh S, et al.: [Leitlinie der Gesellschaft für Thrombose- und Hämostaseforschung (GTH) zur Struktur- und Prozessqualität von Hämophilie-Zentren]. Hamostaseologie 2019; 24.
9.Valentino LA: Considerations in individualizing prophylaxis in patients with haemophilia A. Haemophilia 2014; 20: 607–15 CrossRef MEDLINE
10.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: 535–44 CrossRef MEDLINE
11.Manco-Johnson MJ, Lundin B, Funk S, et al.: Effect of late prophylaxis in hemophilia on joint status: a randomized trial. J Thromb Haemost 2017; 15: 2115–24 CrossRef MEDLINE
12.Gouw SC, van der Bom JG, Auerswald G, et al.: Recombinant versus plasma-derived factor VIII products and the development of inhibitors in previously untreated patients with severe hemophilia A: the CANAL cohort study. Blood 2007; 109: 4693–7 CrossRef CrossRef
13.Mazepa MA, Monahan PE, Baker JR, Riske BK, Soucie JM, US Hemophilia Treatment Center Network: Men with severe hemophilia in the United States: birth cohort analysis of a large national database. Blood 2016; 127: 3073–81 CrossRef MEDLINE PubMed Central
14.Oldenburg J: Optimal treatment strategies for haemophilia: achievements and limitations of current prophylactic regiments. Blood 2015; 125: 2038–44 CrossRef MEDLINE
15.Mahlangu J, Young G, Hermans C, Blanchette V, Berntorp E, Santagostino E: Defining extended half-life rFVIII-A critical review of the evidence. Haemophilia 2018; 24: 348–58 CrossRef MEDLINE
16.Mahlangu JN: Updates in clinical trial data of extended half-life recombinant factor IX products for the treatment of haemophilia B. Ther Adv Hematol 2018; 9: 335–46 CrossRef MEDLINE PubMed Central
17.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: 411–9 CrossRef MEDLINE
18.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, 317–25.
19.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, 126, 1078–85 CrossRef MEDLINE PubMed Central
20.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: 252–61 CrossRef MEDLINE
21.Santagostino E, Martinowitz U, LissitchkovT, 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: 1761–9 CrossRef MEDLINE PubMed Central
22.Powell JS, Pasi KJ, Ragni MV, et al.: Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. N Engl J Med 2013; 369: 2313–23 CrossRef MEDLINE
23.Collins PW, Young G, Knobe K, et al.: Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational randomized phase 3 trial. Blood 2014; 124: 3880–6 CrossRef MEDLINE PubMed Central
24.van den Bossche D, Peerlinck K, Jacquemin M: New challenges and best practices for the laboratory monitoring of factor VIII and factor IX replacement. Int J Lab Hematol 2018; 40 (Suppl 1): 21–9 CrossRef MEDLINE
25.Collins P, Chalmers E, Chowdary P, et al.: The use of enhanced half-life coagulation factor concentrates in routine clinical practice: guidance from UKHCDO. Haemophilia 2016; 22: 487–98 CrossRef MEDLINE
26.Sampei Z, Igawa T, Soeda T, et al.: Identification and multidimensional optimization of an asymmetric bispecific IgG antibody mimicking the function of factor VIII cofactor activity. PLoS One 2013; 8: e57479 CrossRef MEDLINE PubMed Central
27.Oldenburg J, Mahlangu JN, Kim B, et al.: Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med 2017; 377: 809–18 CrossRef MEDLINE
28.Young G, Sidonio RF, Liesner R, et al.: HAVEN 2 updated analysis: multicenter, open-label, phase 3 study to evaluate efficacy, safety and pharmacokinetics of subcutaneous administration of emicizumab prophylaxis in pediatric patients with hemophilia A with inhibitors. Blood 2017; 130: 85.
29.Mahlangu J, Oldenburg J, Paz-Priel I, et al.: Emicizumab prophylaxis in patients who have hemophilia A without inhibitors. N Engl J Med 2018; 379: 811–22 CrossRef MEDLINE
30.Pipe SW, Shima M, Lehle M, et al.: Efficacy, safety, and pharmacokinetics of emicizumab propyhalxis given every 4 weeks in people with haemophilia A (HAVEN 4): a multicentre, open-label, non randomized phase 3 study. Lancet Haematol 2019; 6: e295–305 CrossRef
31.Müller J, Pekrul I, Pötzsch B, Berning B, Oldenburg J, Spannagl M: Laboratory monitoring in emicizumab-treated persons with hemophilia A. Thromb Haemost 2019; 16 CrossRef MEDLINE
32.Eichler H, Angchaisuksiri P, Kavakli K, et al.: Concizumab restores thrombin generation potential in patients with haemophilia: pharmacokinetic/pharmacodynamic modelling results of concizumab phase 1/1b data. Haemophilia 2019; 25: 60–6 CrossRef MEDLINE
33.Pasi KJ, Rangarajan S, Georgiev P, et al.: Targeting of antithrombin in hemophilia A or B with RNAi therapy. N Engl J Med 2017; 377: 819–28 CrossRef MEDLINE
34.Flotte TR, Carter BJ: Adeno-associated virus vectors for gene therapy. Gene Ther 1995; 2: 357–62.
35.Nathwani AC, Tuddenham EG, Rangarajan S, et al.: Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med 2011; 365: 2357–65 CrossRef MEDLINE PubMed Central
36.Nathwani AC, Reiss UM, Tuddenham EG, et al.: Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med 2014; 371: 1994–2004 CrossRef MEDLINE PubMed Central
37.Nienhuis AW, Nathwani AC, Davidoff AM: Gene therapy for hemophilia. Mol Ther 2017; 25: 1163–7 CrossRef MEDLINE PubMed Central
38.George LA, Sullivan SK, Giermasz A, et al.: Hemophilia B gene therapy with a high-specific-activity factor IX variant. N Engl J Med 2017; 377: 2215–27 CrossRef MEDLINE PubMed Central
39.Miesbach W, Meijer K, Coppens M, et al.: Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B. Blood 2018; 131: 1022–31 CrossRef MEDLINE PubMed Central
40.Rangarajan S, Walsh L, Lester W, et al.: Factor VIII gene transfer in severe hemophilia A. N Engl J Med 2017; 377: 2519–30 CrossRef MEDLINE
e1.WFH 2018: Report on the Annual Global Survey 2017. Montreal, Canada.
e2.Scott MJ, Xiang H, Hart DP, et al: Treatment regimens and outcomes in severe and moderate haemophilia A in the UK: the THUNDER study. Haemophilia 2019; 25: 205–12 CrossRef MEDLINE
e3.Haschberger B, Hesse J, Heiden M, Seitz R, Schramm W: [Documentation of haemophilia treatment supported by the German Hemophilia Registry]. Hamostaseologie 2010; 30 (Suppl 1): 62–4.
e4.Gouw SC, van der Bom JG, Marijke van den Berg H: Treatment-related risk factors of inhibitor development in previously untreated patients with hemophilia A: the CANAL cohort study. Blood 2007; 109: 4648–54 CrossRef MEDLINE
e5.Peters RT, Toby G, Lu Q, et al: Biochemical and functional characterization of a recombinant monomeric factor VIII Fc fusion protein. J Thromb Haemost 2013; 11, 132–41 CrossRef MEDLINE PubMed Central
e6.Metzner HJ, Pipe SW, Weimer T, Schulte S: Extending the pharmacokinetic half-life of coagulation factors by fusion to recombinant albumin. Thromb Haemost 2013; 110: 931–9 CrossRef MEDLINE
e7.Mei B, Pan C, Jiang H, et al: Rational design of a fully active, long-acting PEGylated factor VIII for hemophilia A treatment. Blood 2010; 116, 270–9 CrossRef MEDLINE
e8.Terraube V, O‘Donnell JS, Jenkins PV: Factor VIII and von Willebrand factor interaction: biological, clinical and therapeutic importance. Haemophilia 2010; 16: 3–13 CrossRef MEDLINE
e9.Konkle BA, Shapiro A, Quon DV, et al.: BIVV001: The first investigational factor VIII therapy to break through the VWF ceiling in hemophilia A, with potential for extended protection for one week or longer. Presented at 60th Annual American Society of Hematology Meeting and Exposition 1–4 December 2018, San Diego, CA, USA, Blood 2018 CrossRef
e10.Coyle TE, Reding MT, Lin JC, Michaels LA, Shah A, Powell J: Phase I study of BAY 94–9027, a PEGylated B domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A. J Thromb Haemost 2014; 12, 488–96 CrossRef MEDLINE PubMed Central
e11.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, 317–25.
e12.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, 126, 1078–85 CrossRef MEDLINE PubMed Central
e13.Tiede A, Brand B, Fischer R, et al.: Enhancing the pharmacokinetic properties of recombinant factor VIII: first in human trial of glycoPEgylated recombinant factor VIII in patients with hemophilia A. J Thromb Haemost 2013; 11, 670–8 CrossRef MEDLINE
e14.Martinowitz U, Lubetsky A: Phase I/II, open-label, multicenter, safety, efficacy and PK study of a recombinant coagulation factor IX albumin fusion protein (rFIX-FP) in subjects with hemophilia B. Thromb Res 2013; 131 (Suppl 2): S11–4 CrossRef
e15.Powell JS, Pasi KJ, Ragni MV, et al.: Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. N Engl J Med 2013; 369: 2313–23 CrossRef MEDLINE
e16.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: 2695–701 CrossRef MEDLINE
e17.Hermans C, van Damme A, Dolan G, Maes P, Peerlinck K: UK Haemophilia Centre Doctors‘ Organisation guidance on the use of extended-half-life coagulation factor concentrates in routine clinical practice: report of a meeting on their adoption by Belgian haemophilia treaters. Haemophilia 2018; 24: e378–.80 CrossRef MEDLINE
e18.Lorenzoni V, Triulzi I, Turchetti G: Budget impact analysis of the use of extended half-life recombinant factor VIII (efmoroctocog alfa) for the treatment of congenital haemophilia a: the Italian National Health System perspective. BMC Health Serv Res 2018; 18: 596 CrossRef MEDLINE PubMed Central
e19.Henry N, Jovanović J, Schlueter M, Kritikou P, Wilson K, Myrén KJ: Cost-utility analysis of life-long prophylaxis with recombinant factor VIIIFc vs recombinant factor VIII for the management of severe hemophilia A in Sweden. J Med Econ 2018; 21: 318–25 CrossRef MEDLINE
e20.McMullen S, Buckley B, Hall E, Kendter J, Johnston K: Budget impact analysis of prolonged half-life recombinant FVIII therapy for hemophilia in the United States. Value Health 2017; 20: 93–9 CrossRef MEDLINE
e21.Callaghan MU, Negrier C, Paz-Priel I: Emicizumab treatment is efficacious and well tolerated long term in persons with haemophilia A (PwHA) with or without FVIII inhibitors: pooled data from four HAVEN studies. Presented at the International Society on Thrombosis and Haemostasis, Melbourne, Australia, 6–10 July 2019.
e22.Paz-Priel I, Chang T, Asikanius E, et al.: Immunogenicity of emicizumab in people with hemophilia A (PwHA): results from the HAVEN 1–4 studies. Presented at 60th ASH Annual Meeting & Exposition, December 1–4, 2018, San Diego, CA CrossRef
e23.IQWIG: [A19–26] Emicizumab (Hämophilie A) – Nutzenbewertung gemäß § 35a SGB V www.iqwig.de/de/projekte-ergebnisse/projekte/arzneimittelbewertung/2019/a19–26-emicizumab-haemophilie-a-nutzenbewertung-gemaess-35a-sgb-v.11924.html (last accessed on 24 September 2019).
e24.Gemeinsamer Bundesauschuss: Nutzenbewertungsverfahren zum Wirkstoff Emicizumab. www.g-ba.de/bewertungsverfahren/nutzenbewertung/355/ (last accessed on 24 September 2019).
e25.Gemeinsamer Bundesauschuss: Nutzenbewertungsverfahren zum Wirkstoff Emicizumab (neues Anwendungsgebiet: Hämophilie A, ohne Hemmkörper). www.g-ba.de/bewertungsverfahren/nutzenbewertung/449/#beschluesse (last accessed on 24 September 2019).
e26.National Institute for Health and Care Excellence: Commissioning Support Programme. Scope to inform clinical evidence review of:Emicizumab for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with haemophilia A without factor VIII inhibitors. www.nice.org.uk/Media/Default/About/what-we-do/Commissioning-Support-Programme/ID014-emicizumab-scope.pdf. (last accessed on 24 September 2019).
e27.European medicine agency. Fachinformation Emicizumab. www.ema.europa.eu/en/documents/product-information/hemlibra-epar-product-information_de.pdf (last accessed on 24 September 2019).
e28.Boutin S, Monteilhet V, Veron P, et al.: Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors. Hum Gene Ther 2010; 21: 704–12 CrossRef MEDLINE