Pediatric Drugs

, Volume 20, Issue 2, pp 135–151 | Cite as

Pharmacological Management of Hereditary Angioedema with C1-Inhibitor Deficiency in Pediatric Patients

  • Henriette FarkasEmail author
Review Article


Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is a form of bradykinin-mediated angioedema. It is a rare disorder with an onset during childhood in most instances. Therefore, familiarity with the options for the management of pediatric cases is indispensable. The recurrent angioedematous episodes do not respond to conventional treatments and may evolve into a life-threatening condition. In view of the recommendations adopted by international consensus in 2016, patient management and follow-up should be guided by an individualized strategy. During the last decade, various medicinal products with novel modes of action and different posology have been developed for the treatment of C1-INH-HAE. These drugs either inhibit the release of bradykinin (plasma-derived C1-inhibitors, recombinant C1-inhibitors, kallikrein inhibitors) or prevent the released bradykinin from binding to its receptor (bradykinin B2 receptor antagonists). This review summarizes the properties of the medicinal products currently available for the treatment of C1-INH-HAE, the indications for their use in pediatric patients, and the findings of the clinical trials conducted in this patient population. It is concluded by a brief outline of future therapeutic options.



The author wishes to thank Nóra Veszeli, Márta Debreczeni, and Kinga Viktória Kőhalmi PhD students for compiling the list of references to the literature, and for drafting the figure.

Compliance with Ethical Standards


No sources of funding were used to conduct this study or to prepare this manuscript.

Conflict of interest

The author has received honoraria, travel grants and payment for lectures from CSL Behring, Shire, Swedish Orphan Biovitrum, BioCryst, and Pharming, and/or served as a consultant for these companies.


  1. 1.
    Longhurst H, Cicardi M. Hereditary angio-oedema. Lancet. 2012;379(9814):474–81.CrossRefPubMedGoogle Scholar
  2. 2.
    Cicardi M, Agostoni A. Hereditary angioedema. N Engl J Med. 1996;334(25):1666–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Agostoni A, Cicardi M. Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients. Medicine (Baltimore). 1992;71(4):206–15.CrossRefPubMedGoogle Scholar
  4. 4.
    Stoppa-Lyonnet D, Tosi M, Laurent J, Sobel A, Lagrue G, Meo T. Altered C1 inhibitor genes in type I hereditary angioedema. N Engl J Med. 1987;317(1):1–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Rosen FS, Pensky J, Donaldson V, Charache P. Hereditary angioneurotic edema: two genetic variants. Science. 1965;148(3672):957–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Nussberger J, Cugno M, Cicardi M, Agostoni A. Local bradykinin generation in hereditary angioedema. J Allergy Clin Immunol. 1999;104(6):1321–2.CrossRefPubMedGoogle Scholar
  7. 7.
    Kaplan AP, Joseph K. Complement, kinins, and hereditary angioedema: mechanisms of plasma instability when C1 inhibitor is absent. Clin Rev Allergy Immunol. 2016;51(2):207–15.CrossRefPubMedGoogle Scholar
  8. 8.
    Han ED, MacFarlane RC, Mulligan AN, Scafidi J, Davis AE 3rd. Increased vascular permeability in C1 inhibitor-deficient mice mediated by the bradykinin type 2 receptor. J Clin Investig. 2002;109(8):1057–63.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Martinez-Saguer I, Farkas H. Erythema marginatum as an early symptom of hereditary angioedema: case report of 2 newborns. Pediatrics. 2016;137(2):e20152411.CrossRefPubMedGoogle Scholar
  10. 10.
    Bygum A. Hereditary angio-oedema in Denmark: a nationwide survey. Br J Dermatol. 2009;161(5):1153–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Farkas H. Pediatric hereditary angioedema due to C1-inhibitor deficiency. Allergy Asthma Clin Immunol. 2010;6(1):18.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Bork K, Meng G, Staubach P, Hardt J. Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med. 2006;119(3):267–74.CrossRefPubMedGoogle Scholar
  13. 13.
    Speletas M, Szilagyi A, Psarros F, Moldovan D, Magerl M, Kompoti M, et al. Hereditary angioedema: molecular and clinical differences among European populations. J Allergy Clin Immunol. 2015;135(2):570–3.CrossRefPubMedGoogle Scholar
  14. 14.
    Nielsen EW, Johansen HT, Holt J, Mollnes TE. C1 inhibitor and diagnosis of hereditary angioedema in newborns. Pediatr Res. 1994;35(2):184–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Farkas H, Martinez-Saguer I, Bork K, Bowen T, Craig T, Frank M, et al. International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency. Allergy. 2017;72(2):300–313.Google Scholar
  16. 16.
    Bouillet L, Longhurst H, Boccon-Gibod I, Bork K, Bucher C, Bygum A, et al. Disease expression in women with hereditary angioedema. Am J Obstet Gynecol. 2008;199(5):484 (e1-4).CrossRefPubMedGoogle Scholar
  17. 17.
    Bowen T, Cicardi M, Farkas H, Bork K, Longhurst HJ, Zuraw B, et al. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol. 2010;6(1):24.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Cicardi M, Bork K, Caballero T, Craig T, Li HH, Longhurst H, et al. Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group. Allergy. 2012;67(2):147–57.CrossRefPubMedGoogle Scholar
  19. 19.
    Cicardi M, Aberer W, Banerji A, Bas M, Bernstein JA, Bork K, et al. Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy. 2014;69(5):602–16.CrossRefPubMedGoogle Scholar
  20. 20.
    Craig T, Aygoren-Pursun E, Bork K, Bowen T, Boysen H, Farkas H, et al. WAO Guideline for the Management of Hereditary Angioedema. World Allergy Organ J. 2012;5(12):182–99.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Zotter Z, Csuka D, Szabo E, Czaller I, Nebenfuhrer Z, Temesszentandrasi G, et al. The influence of trigger factors on hereditary angioedema due to C1-inhibitor deficiency. Orphanet J Rare Dis. 2014;9:44.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Farkas H, Zotter Z, Csuka D, Szabo E, Nebenfuhrer Z, Temesszentandrasi G, et al. Short-term prophylaxis in hereditary angioedema due to deficiency of the C1-inhibitor–a long-term survey. Allergy. 2012;67(12):1586–93.PubMedGoogle Scholar
  23. 23.
    Farkas H, Csuka D, Zotter Z, Varga L, Fust G. Prophylactic therapy in children with hereditary angioedema. J Allergy Clin Immunol. 2013;131(2):579–82 (e1–2).CrossRefPubMedGoogle Scholar
  24. 24.
    Farkas H, Kőhalmi K, Veszeli N, Varga L. Safety of plasma-derived C1-inhibitor treatment in pediatric patients with hereditary angioedema due to C1-inhibitor deficiency—a long-term survey. J Allergy Clin Immunol. 2017;139(2):p1A–4A, AB1–AB394, 739.Google Scholar
  25. 25.
    Kreuz W, Rusicke E, Martinez-Saguer I, Aygoren-Pursun E, Heller C, Klingebiel T. Home therapy with intravenous human C1-inhibitor in children and adolescents with hereditary angioedema. Transfusion. 2012;52(1):100–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Aygoren-Pursun E, Martinez-Saguer I, Rusicke E, Klingebiel T, Kreuz W. On demand treatment and home therapy of hereditary angioedema in Germany—the Frankfurt experience. Allergy Asthma Clin Immunol. 2010;6(1):21.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Longhurst HJ, Farkas H, Craig T, Aygoren-Pursun E, Bethune C, Bjorkander J, et al. HAE international home therapy consensus document. Allergy Asthma Clin Immunol. 2010;6(1):22.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Bygum A, Andersen KE, Mikkelsen CS. Self-administration of intravenous C1-inhibitor therapy for hereditary angioedema and associated quality of life benefits. Eur J Dermatol. 2009;19(2):147–51.PubMedGoogle Scholar
  29. 29.
    Abdel-Karim O, Dizdarevic A, Bygum A. Hereditary angioedema: children should be considered for training in self-administration. Pediatr Dermatol. 2014;31(6):e132–5.CrossRefPubMedGoogle Scholar
  30. 30.
    Farkas H, Varga L, Szeplaki G, Visy B, Harmat G, Bowen T. Management of hereditary angioedema in pediatric patients. Pediatrics. 2007;120(3):e713–22.CrossRefPubMedGoogle Scholar
  31. 31.
    Brackertz D, Kueppers F. Hereditary angioneurotic oedema. Lancet. 1973;2(7830):680.CrossRefPubMedGoogle Scholar
  32. 32.
    Berinert® US prescribing information. Revised: Sep 2016.
  33. 33.
    Ebo DG, Verweij MM, De Knop KJ, Hagendorens MM, Bridts CH, De Clerck LS, et al. Hereditary angioedema in childhood: an approach to management. Paediatr Drugs. 2010;12(4):257–68.CrossRefPubMedGoogle Scholar
  34. 34.
    Farkas H, Harmat G, Fust G, Varga L, Visy B. Clinical management of hereditary angio-oedema in children. Pediatr Allergy Immunol. 2002;13(3):153–61.CrossRefPubMedGoogle Scholar
  35. 35.
    Farkas H, Jakab L, Temesszentandrasi G, Visy B, Harmat G, Fust G, et al. Hereditary angioedema: a decade of human C1-inhibitor concentrate therapy. J Allergy Clin Immunol. 2007;120(4):941–7.CrossRefPubMedGoogle Scholar
  36. 36.
    Craig TJ, Schneider LC, MacGinnitie AJ. Plasma-derived C1-INH for managing hereditary angioedema in pediatric patients: a systematic review. Pediatr Allergy Immunol. 2015;26(6):537–44.CrossRefPubMedGoogle Scholar
  37. 37.
    Martinez-Saguer I, Rusicke E, Aygoren-Pursun E, von Hentig N, Klingebiel T, Kreuz W. Pharmacokinetic analysis of human plasma-derived pasteurized C1-inhibitor concentrate in adults and children with hereditary angioedema: a prospective study. Transfusion. 2010;50(2):354–60.CrossRefPubMedGoogle Scholar
  38. 38.
    Craig TJ, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz D, Obtulowicz K, et al. Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. J Allergy Clin Immunol. 2009;124(4):801–8.CrossRefPubMedGoogle Scholar
  39. 39.
    Craig TJ, Bewtra AK, Bahna SL, Hurewitz D, Schneider LC, Levy RJ, et al. C1 esterase inhibitor concentrate in 1085 hereditary angioedema attacks–final results of the I.M.P.A.C.T.2 study. Allergy. 2011;66(12):1604–11.CrossRefPubMedGoogle Scholar
  40. 40.
    Schneider L, Hurewitz D, Wasserman R, Obtulowicz K, Machnig T, Moldovan D, et al. C1-INH concentrate for treatment of acute hereditary angioedema: a pediatric cohort from the I.M.P.A.C.T. studies. Pediatr Allergy Immunol. 2013;24(1):54–60.CrossRefPubMedGoogle Scholar
  41. 41.
    Farkas H, Varga L, Moldovan D, Obtulowicz K, Shirov T, Machnig T, et al. Assessment of inhibitory antibodies in patients with hereditary angioedema treated with plasma-derived C1 inhibitor. Ann Allergy Asthma Immunol. 2016;117(5):508–13.CrossRefPubMedGoogle Scholar
  42. 42.
    Busse P, Baker J, Martinez-Saguer I, Bernstein JA, Craig T, Magerl M, et al. Safety of C1-inhibitor concentrate use for hereditary angioedema in pediatric patients. J Allergy Clin Immunol Pract. 2017;5(4):1142–5.CrossRefPubMedGoogle Scholar
  43. 43.
  44. 44.
    Lumry W, Manning ME, Hurewitz DS, Davis-Lorton M, Fitts D, Kalfus IN, et al. Nanofiltered C1-esterase inhibitor for the acute management and prevention of hereditary angioedema attacks due to C1-inhibitor deficiency in children. J Pediatr. 2013;162(5):1017–22 (e1–2).CrossRefPubMedGoogle Scholar
  45. 45.
    Schranz J, Ledford D, Gower R, Soteres D, Jacobson KW, Li H, et al. Safety and efficacy of C1 esterase inhibitor for acute attacks in children with hereditary angioedema less than 12 years of age. Special issue: abstracts from the European Academy of Allergy and Clinical Immunology Congress, 7–11 June 2014, Copenhagen, Denmark. Allergy. 2014;69(Issue Supplement s99):1–646.Google Scholar
  46. 46.
    Hack CE, Relan A, van Amersfoort ES, Cicardi M. Target levels of functional C1-inhibitor in hereditary angioedema. Allergy. 2012;67(1):123–30.CrossRefPubMedGoogle Scholar
  47. 47.
    Farkas H, Aygören-Pürsün E, Martinez-Saguer I, Kessel A, Hao J, Lu P, et al. The use of a C1 esterase inhibitor concentrate to manage hereditary angioedema attacks is children. European Academy of Allergy and Clinical Immunology Congress, 17–21 June 2017. Helsinki, Finnland. Oral Abstract Session (OAS 27). 2017.Google Scholar
  48. 48.
    Lumry W, Soteres D, Gower R, Jacobson KW, Li HH, Chen H, et al. Safety and efficacy of C1 esterase inhibitor for acute attacks in children with hereditary angioedema. Pediatr Allergy Immunol. 2015;26(7):674–80.CrossRefPubMedGoogle Scholar
  49. 49.
    Grant JA, White MV, Li HH, Fitts D, Kalfus IN, Uknis ME, et al. Preprocedural administration of nanofiltered C1 esterase inhibitor to prevent hereditary angioedema attacks. Allergy Asthma Proc. 2012;33(4):348–53.CrossRefPubMedGoogle Scholar
  50. 50.
    Aygoren-Pursun E, Soteres D, Moldovan D, Christensen J, Van Leerberghe A, Hao J, et al. Preventing hereditary angioedema attacks in children using Cinryze(R): interim efficacy and safety phase 3 findings. Int Arch Allergy Immunol. 2017;173(2):114–9.CrossRefPubMedGoogle Scholar
  51. 51.
    Zuraw BL, Cicardi M, Longhurst HJ, Bernstein JA, Li HH, Magerl M, et al. Phase II study results of a replacement therapy for hereditary angioedema with subcutaneous C1-inhibitor concentrate. Allergy. 2015;70(10):1319–28.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Longhurst H, Cicardi M, Craig T, Bork K, Grattan C, Baker J, et al. Prevention of hereditary angioedema attacks with a subcutaneous C1 inhibitor. N Engl J Med. 2017;376(12):1131–40.CrossRefPubMedGoogle Scholar
  53. 53.
    A study to evaluate the long-term clinical safety and efficacy of subcutaneously administered C1-esterase inhibitor in the prevention of hereditary angioedema. Accessed 2 Aug 2017.
  54. 54.
    Relan A, Bakhtiari K, van Amersfoort ES, Meijers JC, Hack CE. Recombinant C1-inhibitor: effects on coagulation and fibrinolysis in patients with hereditary angioedema. BioDrugs. 2012;26(1):43–52.CrossRefPubMedGoogle Scholar
  55. 55.
    van Veen HA, Koiter J, Vogelezang CJ, van Wessel N, van Dam T, Velterop I, et al. Characterization of recombinant human C1 inhibitor secreted in milk of transgenic rabbits. J Biotechnol. 2012;162(2–3):319–26.CrossRefPubMedGoogle Scholar
  56. 56.
    Ruconest (C1 esterase inhibitor [recombinant]). Full prescribing information. Accessed 2 Aug 2017.
  57. 57.
    Farrell C, Hayes S, Relan A, van Amersfoort ES, Pijpstra R, Hack CE. Population pharmacokinetics of recombinant human C1 inhibitor in patients with hereditary angioedema. Br J Clin Pharmacol. 2013;76(6):897–907.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Baker JW, Reshef A, Moldovan D, Harper JR, Relan A, Riedl MA. Recombinant human C1-esterase inhibitor to treat acute hereditary angioedema attacks in adolescents. J Allergy Clin Immunol Pract. 2017;5(4):1091–7.CrossRefPubMedGoogle Scholar
  59. 59.
    Bernstein JA, Relan A, Harper JR, Riedl M. Sustained response of recombinant human C1 esterase inhibitor for acute treatment of hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2017;118(4):452–5.CrossRefPubMedGoogle Scholar
  60. 60.
    Reshef A, Grivcheva-Panovska V, Kivity S, Klimaszewska-Rembiasz M, Moldovan D, Bellizzi L, et al. Safety and efficacy of rhC1-INH for the treatment of HAE attacks in pediatric patients. Annual Scientific Meeting of American College of Allergy, Asthma & Immunology, November 5–9, 2015. San Antonio (Texas). Annals of Allergy, Asthma & Immunology. 2015.Google Scholar
  61. 61.
    Riedl MA, Grivcheva-Panovska V, Moldovan D, Baker J, Yang WH, Giannetti BM, et al. Recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema: a phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial. Lancet. 2017;390(10102):1595–602.Google Scholar
  62. 62.
    Schneider L, Lumry W, Vegh A, Williams AH, Schmalbach T. Critical role of kallikrein in hereditary angioedema pathogenesis: a clinical trial of ecallantide, a novel kallikrein inhibitor. J Allergy Clin Immunol. 2007;120(2):416–22.CrossRefPubMedGoogle Scholar
  63. 63.
    KALBITOR® (ecallantide). Full prescribing information.
  64. 64.
    Cicardi M, Levy RJ, McNeil DL, Li HH, Sheffer AL, Campion M, et al. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med. 2010;363(6):523–31.CrossRefPubMedGoogle Scholar
  65. 65.
    Levy RJ, Lumry WR, McNeil DL, Li HH, Campion M, Horn PT, et al. EDEMA4: a phase 3, double-blind study of subcutaneous ecallantide treatment for acute attacks of hereditary angioedema. Ann Allergy Asthma Immunol. 2010;104(6):523–9.CrossRefPubMedGoogle Scholar
  66. 66.
    Lumry WR, Bernstein JA, Li HH, MacGinnitie AJ, Riedl M, Soteres DF, et al. Efficacy and safety of ecallantide in treatment of recurrent attacks of hereditary angioedema: open-label continuation study. Allergy Asthma Proc. 2013;34(2):155–61.CrossRefPubMedGoogle Scholar
  67. 67.
    MacGinnitie AJ, Davis-Lorton M, Stolz LE, Tachdjian R. Use of ecallantide in pediatric hereditary angioedema. Pediatrics. 2013;132(2):e490–7.CrossRefPubMedGoogle Scholar
  68. 68.
    Bernstein JA, Qazi M. Ecallantide: its pharmacology, pharmacokinetics, clinical efficacy and tolerability. Expert Rev Clin Immunol. 2010;6(1):29–39.CrossRefPubMedGoogle Scholar
  69. 69.
    Study to assess the tolerability and safety of ecallantide in children and adolescents with hereditary angioedema. Accessed 4 Aug 2017.
  70. 70.
    Hock FJ, Wirth K, Albus U, Linz W, Gerhards HJ, Wiemer G, et al. Hoe 140 a new potent and long acting bradykinin-antagonist: in vitro studies. Br J Pharmacol. 1991;102(3):769–73.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Cicardi M, Banerji A, Bracho F, Malbran A, Rosenkranz B, Riedl M, et al. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010;363(6):532–41.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    ANNEX I. Summary of product characteristics. Firazyr 30 mg solution for injection in pre-filled syringe. Accessed 4 Aug 2017.
  73. 73.
    FIRAZYR® (icatibant). Full prescribing information (2011) Accessed 4 Aug 2017.
  74. 74.
    Farkas H, Reshef A, Aberer W, Caballero T, McCarthy L, Hao J, et al. Treatment effect and safety of icatibant in pediatric patients with hereditary angioedema. J Allergy Clin Immunol Pract. 2017;5(6):1671–1678.e2.Google Scholar
  75. 75.
    Leach JK, Spencer K, Mascelli M, McCauley TG. Pharmacokinetics of single and repeat doses of icatibant. Clin Pharmacol Drug Dev. 2015;4(2):105–11.CrossRefPubMedGoogle Scholar
  76. 76.
    Hanizah N, Affirul CA, Farah NA, Shamila MA, Ridzuan MI. Novel usage of fresh frozen plasma in hereditary angioedema. Clin Ter. 2016;167(6):182–4.PubMedGoogle Scholar
  77. 77.
    Gelfand JA, Sherins RJ, Alling DW, Frank MM. Treatment of hereditary angioedema with danazol. Reversal of clinical and biochemical abnormalities. N Engl J Med. 1976;295(26):1444–8.CrossRefPubMedGoogle Scholar
  78. 78.
    Pappalardo E, Zingale LC, Cicardi M. Increased expression of C1-inhibitor mRNA in patients with hereditary angioedema treated with Danazol. Immunol Lett. 2003;86(3):271–6.CrossRefPubMedGoogle Scholar
  79. 79.
    Longhurst H, Zinser E. Prophylactic therapy for hereditary angioedema. Immunol Allergy Clin North Am. 2017;37(3):557–70.CrossRefPubMedGoogle Scholar
  80. 80.
    Riedl MA. Critical appraisal of androgen use in hereditary angioedema: a systematic review. Ann Allergy Asthma Immunol. 2015;114(4):281–8 (e7).CrossRefPubMedGoogle Scholar
  81. 81.
    Barakat A, Castaldo AJ. Hereditary angioedema: danazol therapy in a 5-year-old child. Am J Dis Child. 1993;147(9):931–2.PubMedGoogle Scholar
  82. 82.
    Church JA. Oxandrolone treatment of childhood hereditary angioedema. Ann Allergy Asthma Immunol. 2004;92(3):377–8.CrossRefPubMedGoogle Scholar
  83. 83.
    Kohalmi KV, Veszeli N, Luczay A, Varga L, Farkas H. Effect of danazol treatment on growth in pediatric patients with hereditary angioedema due to C1-inhibitor deficiency. Orv Hetil. 2017;158(32):1269–76.CrossRefPubMedGoogle Scholar
  84. 84.
    Saule C, Boccon-Gibod I, Fain O, Kanny G, Plu-Bureau G, Martin L, et al. Benefits of progestin contraception in non-allergic angioedema. Clin Exp Allergy. 2013;43(4):475–82.CrossRefPubMedGoogle Scholar
  85. 85.
    Kessel A, Farkas H, Kivity S, Veszeli N, Kohalmi KV, Engel-Yeger B. The relationship between anxiety and quality of life in children with hereditary angioedema. Pediatr Allergy Immunol. 2017;28(7):692–698.Google Scholar
  86. 86.
    Engel-Yeger B, Farkas H, Kivity S, Veszeli N, Kohalmi KV, Kessel A. Health-related quality of life among children with hereditary angioedema. Pediatr Allergy Immunol. 2017;28(4):370–6.CrossRefPubMedGoogle Scholar
  87. 87.
    Cornpropst M, Collis P, Collier J, Babu YS, Wilson R, Zhang J, et al. Safety, pharmacokinetics, and pharmacodynamics of avoralstat, an oral plasma kallikrein inhibitor: phase 1 study. Allergy. 2016;71(12):1676–83.CrossRefPubMedGoogle Scholar
  88. 88.
    Aygoren-Pursun E, Magerl M, Graff J, Martinez-Saguer I, Kreuz W, Longhurst H, et al. Prophylaxis of hereditary angioedema attacks: a randomized trial of oral plasma kallikrein inhibition with avoralstat. J Allergy Clin Immunol. 2016;138(3):934–6 (e5).CrossRefPubMedGoogle Scholar
  89. 89.
    Aygoeren-Pursun E, Bygum A, Steiner UC, Magerl M, Grivcheva-Panovska V, Farkas H, et al. Bcx7353, a once-daily oral kallikrein inhibitor, is effective and safe in the prophylaxis of acute attacks in patients with hereditary angioedema: attack-level analysis of the apex-1 study. Abstracts from the 10th C1-inhibitor deficiency workshop (O-15). 18–21 May 2017, Budapest (Hungary). Allergy Asthma Clin Immunol. 2017, vol 13, no Suppl 2.Google Scholar
  90. 90.
    Kenniston JA, Faucette RR, Martik D, Comeau SR, Lindberg AP, Kopacz KJ, et al. Inhibition of plasma kallikrein by a highly specific active site blocking antibody. J Biol Chem. 2014;289(34):23596–608.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Chyung Y, Vince B, Iarrobino R, Sexton D, Kenniston J, Faucette R, et al. A phase 1 study investigating DX-2930 in healthy subjects. Ann Allergy Asthma Immunol. 2014;113(4):460–6 (e2).CrossRefPubMedGoogle Scholar
  92. 92.
    Banerji A, Busse P, Shennak M, Lumry W, Davis-Lorton M, Wedner HJ, et al. Inhibiting plasma kallikrein for hereditary angioedema prophylaxis. N Engl J Med. 2017;376(8):717–28.CrossRefPubMedGoogle Scholar
  93. 93.
  94. 94.
    Bhattacharjee G, Revenko AS, Crosby JR, May C, Gao D, Zhao C, et al. Inhibition of vascular permeability by antisense-mediated inhibition of plasma kallikrein and coagulation factor 12. Nucl Acid Ther. 2013;23(3):175–87.CrossRefGoogle Scholar
  95. 95.
    Bork K. A decade of change: recent developments in pharmacotherapy of hereditary angioedema (HAE). Clin Rev Allergy Immunol. 2016;51(2):183–92.CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  1. 1.3rd Department of Internal Medicine, Hungarian Angioedema CenterSemmelweis UniversityBudapestHungary

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