A Decade of Change: Recent Developments in Pharmacotherapy of Hereditary Angioedema (HAE)

Clin Rev Allergy Immunol. 2016 Oct;51(2):183-92. doi: 10.1007/s12016-016-8544-9.


Hereditary angioedema (HAE) due to C1 esterase inhibitor (C1-INH) deficiency (HAE-C1-INH) is a rare but medically significant disease that can be associated with considerable morbidity and mortality. Research into the pathogenesis of HAE-C1-INH has expanded greatly in the last six decades and has led to new clinical trials with novel therapeutic agents and treatment strategies. Mechanisms of pharmacotherapy include (a) supplementing C1-INH, the missing serine-protease inhibitor in HAE; (b) inhibiting the activation of the contact system and the uncontrolled release of proteases in the kallikrein-kinin system, by blocking the production/function of its components; (c) inhibiting the fibrinolytic system by blocking the production/function of its components; and (d) inhibiting the function of bradykinin at the endothelial level. Strategies for managing HAE-C1-INH are aimed at treating acute attacks, or preventing attacks, through the use of prophylactic treatment. Available agents for treating acute attacks include plasma-derived C1-INH concentrates, a recombinant C1-INH, a bradykinin B2 receptor antagonist, and a plasma kallikrein inhibitor. Long-term prophylactic treatments include attenuated androgens, plasma-derived C1-INH concentrates, and anti-fibrinolytics. Plasma-derived C1-INH and a bradykinin B2 receptor antagonist are already approved for self-administration at home. The number of management options for HAE-C1-INH has increased considerably within the past decade, thus helping to alleviate the burden of this rare disease.

Keywords: C1 inhibitor; C1-INH deficiency; Hereditary angioedema; Prophylaxis; Treatment for acute attacks.

Publication types

  • Review

MeSH terms

  • Angioedemas, Hereditary / drug therapy*
  • Angioedemas, Hereditary / etiology
  • Angioedemas, Hereditary / metabolism
  • Angioedemas, Hereditary / prevention & control
  • Antifibrinolytic Agents / therapeutic use
  • Bradykinin Receptor Antagonists / therapeutic use
  • Complement C1 Inhibitor Protein / therapeutic use
  • Disease Progression
  • Humans
  • Kallikreins / antagonists & inhibitors
  • Kinins / antagonists & inhibitors
  • Premedication


  • Antifibrinolytic Agents
  • Bradykinin Receptor Antagonists
  • Complement C1 Inhibitor Protein
  • Kinins
  • Kallikreins