title: A Decade of Change: Recent Developments in Pharmacotherapy of Hereditary Angioedema (HAE).
abstract: 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.
authors.affiliation: Department of Dermatology, Johannes Gutenberg University, Langenbeckstr 1, 55131, Mainz, Germany. bork@hautklinik.klinik.uni-mainz.de.
authors.forename: Konrad
authors.initials: K
authors.lastname: Bork
mesh_terms: D054179:Angioedemas, Hereditary / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D000933:Antifibrinolytic Agents / Q000627:therapeutic use; D065168:Bradykinin Receptor Antagonists / Q000627:therapeutic use; D050718:Complement C1 Inhibitor Protein / Q000627:therapeutic use; D018450:Disease Progression; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors; D007705:Kinins / Q000037:antagonists & inhibitors; D011292:Premedication
chemical_list: D000933:Antifibrinolytic Agents; D065168:Bradykinin Receptor Antagonists; D050718:Complement C1 Inhibitor Protein; D007705:Kinins; D007610:Kallikreins
keywords: C1 inhibitor; C1-INH deficiency; Hereditary angioedema; Prophylaxis; Treatment for acute attacks