XXXIII Congreso Nacional de la Sociedad Española de Trombosis y Hemostasia

XXXIII Congreso Nacional de la Sociedad Española de Trombosis y Hemostasia 46 Desventajas Posiblemente, lo único que puede ensombrecer esta terapia disruptiva para los pacientes con hemofilia, son los eventos trom- boembólicos y el desarrollo de MIT aparecidos en pacientes que han recibido concomitantemente emicizumab y CCPa en el con- texto de los ensayos clínicos. Bibliografía 1. Nilsson IM, et al. Twenty-five years’ experience of prophy- lactic treatment in severe haemophilia A and B. J Intern Med 1992;232(1):25-32. 2. Manco-Johnson MJ, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 2007;357(6):535-44. 3. Gringeri A, et al. A randomized clinical trial of prophylaxis in chil- dren with hemophilia A (the ESPRIT Study). J Thromb Haemost 2011;9(4):700-10. 4. Gouw SC, et al. Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study. Blood 2013;121(20): 4046-55. 5. Berntorp E. Haemophilia treatment in 2030. Haemophilia 2016;22(Suppl 5):15-9. 6. Wang W, Wang EQ, and Balthasar JP. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 2008;84(5):548-58. 7. Baker MP, et al. Immunogenicity of protein therapeutics: The key causes, consequences and challenges. Self Nonself 2010;1(4):314-22. 8. Kitazawa T, et al. A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model. Nat Med 2012;18(10):1570-4. 9. Muto A, et al. Anti-factor IXa/X bispecific antibody ACE910 pre- vents joint bleeds in a long-term primate model of acquired hemo- philia A. Blood 2014;124(20):3165-71. 10. Uchida N, et al. A first-in-human phase 1 study of ACE910, a novel factor VIII-mimetic bispecific antibody, in healthy subjects. Blood 2016;127(13):1633-41. 11. Hartmann R, Knappe S, Ewenstein BM, Valentino L, Scheiflinger F. Synergistic Effects of a Procoagulant Bispecific Antibody and FEI- BA or Factor VIIa on Thrombin Generation. Blood 2016;128:4952. 12. Adamkewicz O, Soeda T, Suzkisachiyo ,Takehisakitazawa. In vitro thrombin generation testing and in vivo venous stasis model for assessing the pro-coagulant effects of FVIII. Emicizumab; rFVIIa and aPCC. Haemophilia 2017;23(2):11-27. 13. Hilden I, et al. Hemostatic effect of a monoclonal antibody mAb 2021 blocking the interaction between FXa and TFPI in a rabbit hemophilia model. Blood 2012;119(24):5871-8. 14. Chowdary P, et al. Safety and pharmacokinetics of anti-TFPI antibody (concizumab) in healthy volunteers and patients with hemophilia: a ran- domized first human dose trial. J Thromb Haemost 2015;13(5):743-54. 15. Ragni MV. Targeting Antithrombin to Treat Hemophilia. N Engl J Med 2015;373(4):389-91. 16. Bolliger D, et al. Heterozygous antithrombin deficiency improves in vivo haemostasis in factor VIII-deficient mice. Thromb Haemost 2010;103(6):1233-8. 17. Sehgal A, et al. An RNAi therapeutic targeting antithrombin to rebal- ance the coagulation system and promote hemostasis in hemophilia. Nat Med 2015;21(5):492-7. 18. Pasi KJ. Fitusiran, an Investigational rnai therapeutic targeting anti- thrombin for the treatment of hemophilia: updated results from a phase 1 and phase 1/2 extension study in patients with inhibitors. Abstract 1397 58th ASHAnnual Meeting & Exposition. San Diego, California; 2015. 19. Berntorp E, Shapiron AD. Modern haemophilia care. Lancet 2012;379(9824):1447-56.