Icatibant, a New Bradykinin-Receptor Antagonist, in Hereditary Angioedema

• Published in: The New England journal of medicine Vol. 363; no. 6; pp. 532 - 541
• Main Authors: Cicardi, Marco, Banerji, Aleena, Bracho, Francisco, Malbrán, Alejandro, Rosenkranz, Bernd, Riedl, Marc, Bork, Konrad, Lumry, William, Aberer, Werner, Bier, Henning, Bas, Murat, Greve, Jens, Hoffmann, Thomas K, Farkas, Henriette, Reshef, Avner, Ritchie, Bruce, Yang, William, Grabbe, Jürgen, Kivity, Shmuel, Kreuz, Wolfhart, Levy, Robyn J, Luger, Thomas, Obtulowicz, Krystyna, Schmid-Grendelmeier, Peter, Bull, Christian, Sitkauskiene, Brigita, Smith, William B, Toubi, Elias, Werner, Sonja, Anné, Suresh, Björkander, Janne, Bouillet, Laurence, Cillari, Enrico, Hurewitz, David, Jacobson, Kraig W, Katelaris, Constance H, Maurer, Marcus, Merk, Hans, Bernstein, Jonathan A, Feighery, Conleth, Floccard, Bernard, Gleich, Gerald, Hébert, Jacques, Kaatz, Martin, Keith, Paul, Kirkpatrick, Charles H, Langton, David, Martin, Ludovic, Pichler, Christiane, Resnick, David, Wombolt, Duane, Romero, Diego S. Fernández, Zanichelli, Andrea, Arcoleo, Francesco, Knolle, Jochen, Kravec, Irina, Dong, Liying, Zimmermann, Jens, Rosen, Kimberly, Fan, Wing-Tze
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 05.08.2010
• Subjects: Acute Disease; Adult; Airway management; Allergic diseases; Angioedema; Angioedemas, Hereditary - drug therapy; Biological and medical sciences; Bradykinin - administration & dosage; Bradykinin - adverse effects; Bradykinin - analogs & derivatives; Bradykinin - therapeutic use; Bradykinin B2 Receptor Antagonists; Clinical Medicine; Data collection; Double-Blind Method; Female; General aspects; Humans; Immunopathology; Injections, Subcutaneous; Intention to Treat Analysis; Klinisk medicin; Lungmedicin och allergi; Male; Medical and Health Sciences; Medical research; Medical sciences; Medicin och hälsovetenskap; Respiratory Medicine and Allergy; Skin allergic diseases. Stinging insect allergies; Statistics, Nonparametric; Studies; Tranexamic Acid - therapeutic use; Medicine; Allergy; Immunopathology; Skin disease; Angioneurotic edema; Bradykinin antagonist; Hereditary; B2 bradykinin receptor; Icatibant; Hormonal receptor; Genetic disease; Biological receptor
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa0906393

Two randomized trials evaluated the effect of the bradykinin-receptor antagonist icatibant in patients with hereditary angioedema presenting with acute attacks. The primary end point in each trial was the median time to clinically significant relief of symptoms. In one trial, the primary end point was reached significantly faster with icatibant than with tranexamic acid. In the other trial, the primary end point was not reached significantly faster with icatibant than with placebo. Hereditary angioedema is an autosomal dominant disorder caused by a deficiency of C1 esterase inhibitor, which has a regulatory role in the classic complement pathway and in the coagulation, fibrinolytic, and kallikrein–kinin (contact-system) cascades. Reduced activity of C1 esterase inhibitor may result in an elevated plasma level of bradykinin, 1 , 2 the key mediator of symptoms in hereditary angioedema. 3 , 4 Patients with hereditary angioedema present with acute attacks of subcutaneous and submucosal edema that can affect the upper airways, face, extremities, genitals, and gastrointestinal tract. 5 – 7 Pharyngolaryngeal edema, which is potentially life-threatening because of the risk of upper-airway obstruction, can also . . .