Icatibant, an inhibitor of bradykinin receptor 2, for hereditary angioedema attacks
prospective experimental single-cohort study
Keywords:
Angioedemas, hereditary, Complement C1 inhibitor protein, Therapy [subheading], Receptors, bradykinin, BradykininAbstract
CONTEXT AND OBJECTIVE: Hereditary angioedema (HAE) with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil. DESIGN AND SETTING: Prospective experimental single-cohort study on the efficacy and safety of icatibant for HAE patients. METHODS: Patients with a confirmed HAE diagnosis were enrolled according to symptoms and regardless of the time since onset of the attack. Icatibant was administered in accordance with the protocol that has been approved in Brazil. Symptom severity was assessed continuously and adverse events were monitored. RESULTS: 24 attacks in 20 HAE patients were treated (female/male 19:1; 19-55 years; median 29 years of age). The symptoms were: subcutaneous edema (22/24); abdominal pain (15/24) and upper airway obstruction (10/24). The time taken until onset of relief was: 5-10 minutes (5/24; 20.8%); 10-20 (5/24; 20.8%); 20-30 (8/24; 33.4%); 30-60 (5/24; 20.8%); and 2 hours (1/24; 4.3%). The time taken for complete resolution of symptoms ranged from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites. Mild to moderate erythema and/or feelings of burning were reported by 15/24 patients, itching by 3 and no adverse effects in 6. CONCLUSION: HAE type I patients who received icatibant responded promptly; most achieved improved symptom severity within 30 minutes. Local adverse events occurred in 75% of the patients.
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References
Giavina-Bianchi P, França AT, Grumach AS, et al. Brazilian guidelines for the diagnosis and treatment of hereditary angioedema. Clinics (Sao Paulo). 2011;66(9):1627-36.
Bowen T, Cicardi M, Farkas H, et al. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol. 2010;6(1):24.
Bork K, Siedlecki K, Bosch S, Schopf RE, Kreuz W. Asphyxiation by laryngeal edema in patients with hereditary angioedema. Mayo Clin Proc. 2000;75(4):349-54.
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.
Kaplan AP. Bradykinin and the pathogenesis of hereditary angioedema. World Allergy Organ J. 2011;4(4):73-5.
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 Invest. 2002;109(8):1057-63.
Nussberger J, Cugno M, Amstutz C, et al. Plasma bradykinin in angio- oedema. Lancet. 1998;351(9117):1693-7.
Cicardi M, Banerji A, Bracho F, et al. Icatibant, a new bradykinin- receptor antagonist, in hereditary angioedema. N Engl J Med. 2010;363(6):532-41.
Longhurst HJ. Management of acute attacks of hereditary angioedema: potential role of icatibant. Vasc Health Risk Manag. 2010;6:795-802.
Lumry WR, Li HH, Levy RJ, et al. Randomized placebo-controlled trial of the bradykinin B2 receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial. Ann Allergy Asthma Immunol. 2011;107(6):529-37.
Greve J, Hoffmann TK, Schuler P, et al. Successful long-term treatment with the bradykinin B2 receptor antagonist icatibant in a patient with hereditary angioedema. Int J Dermatol. 2011;50(10):1294-5.
Farkas H, Csuka D, Zotter Z, et al. Home treatment of hereditary angioedema with icatibant administered by heath care professionals. J Allergy Clin Immunol. 2012;129(3):851-852.e2.
Boccon-Gibod I, Bouillet L. Safety and efficacy of icatibant self- administration for acute hereditary angioedema. Clin Exp Immunol. 2012;168(3):303-7.
Cicardi M, Bork K, Caballero T, 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.
Maurer M, Magerl M. Long-term prophylaxis of hereditary angioedema with androgen derivatives: a critical appraisal and potential alternatives. J Dtsch Dermatol Ges. 2011;9(2):99-107.
Maurer M, Church MK. Inflammatory skin responses induced by icatibant injection are mast cell mediated and attenuated by H(1)- antihistamines. Exp Dermatol. 2012;21(2):154-5.
Malbrán A, Fernández Romero DS, Menéndez A. Angioedema hereditario. Guia de Tratamiento. Medicina (Buenos Aires). 2012;72(2):119-23.
Grumach AS, Valle SO, Toledo E, et al. Hereditary angioedema: first report of the Brazilian registry and challenges. J Eur Acad Dermatol Venereol. 2013;27(3):e338-44.
Marqués L, Domingo D, Maravall FJ, Clotet J. Short-term prophylactic treatment of hereditary angioedema with icatibant. Allergy. 2010;65(1):137-8.
Zanichelli A, Vacchini R, Badini M, Penna V, Cicardi M. Standard care impact on angioedema because of hereditary C1 inhibitor deficiency: a 21-month prospective study in a cohort of 103 patients. Allergy. 2011;66(2):192-6.
Bork K, Frank J, Grundt B, et al. Treatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (Icatibant). J Allergy Clin Immunol. 2007;119(6):1497-503.
Wilson DA, Bork K, Shea EP, et al. Economic costs associated with acute attacks and long-term management of hereditary angioedema. Ann Allergy Asthma Immunol. 2010;104(4):314-20.
