Update on therapeutic developments for hereditary angioedema.
Remarkable progress has been made in understanding the molecular mechanisms underlying attacks of swelling in hereditary angioedema (HAE). Treatment options in the United States for this potentially life-threatening disease had remained essentially static, however, over the past 40 years. Prophylactic therapy had relied on attenuated androgens or antifibrinolytic agents. Although demonstrably effective, these drugs have been fraught with side effects. Acute therapy has been largely relegated to supportive care. In this article we discuss emerging treatments that have evolved from the recognition that kinin generation is the fundamental abnormality leading to attacks of angioedema. We will review the newly approved replacement therapy for prophylaxis of HAE attacks with C1 inhibitor (C1INH). Potential options for the acute treatment of HAE will be discussed including purified C1INH, recombinant C1INH, an inhibitor of plasma kallikrein, and a B2-receptor antagonist. The arrival of these novel therapies promises to transform the future management of HAE.
Department of Allergy, Kaiser Permanente and Department of Medicine, University of California San Diego, La Jolla, California, USA. sandra.c.christiansen@kp.org
Sandra C
SC
Christiansen
Bruce L
BL
Zuraw
D054179:Angioedemas, Hereditary / Q000188:drug therapy*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D065168:Bradykinin Receptor Antagonists; D002199:Capillary Permeability / Q000187:drug effects / Q000276:immunology; D002986:Clinical Trials as Topic; D050718:Complement C1 Inhibitor Protein / Q000008:administration & dosage / Q000627:therapeutic use*; D056947:Enzyme Replacement Therapy; D006801:Humans; D020842:Plasma Kallikrein / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D018002:Receptors, Bradykinin / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use*
D065168:Bradykinin Receptor Antagonists; D050718:Complement C1 Inhibitor Protein; D018002:Receptors, Bradykinin; D011994:Recombinant Proteins; C065679:icatibant; D020842:Plasma Kallikrein; D001920:Bradykinin