Prophylaxis with anti-activated factor XII for hereditary angioedema

Abstract

Hereditary angioedema is a rare autosomal dominant genetic disorder characterised by recurrent, localised swellings in various tissues including the skin, genitals, abdomen, face, and oropharyngeal region. These attacks can be painful, debilitating, and life-threatening, substantially affecting quality of life. 1 Banerji A The burden of illness in patients with hereditary angioedema. Ann Allergy Asthma Immunol. 2013; 111: 329-336 Google Scholar , 2 Bork K Hardt J Witzke G Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol. 2012; 130: 692-697 Google Scholar Inadequate control of the contact system, consisting of factor XII (FXII), plasma kallikrein, and high molecular weight kininogen, results in excessive bradykinin formation, which increases vascular permeability and thus causes angioedema attacks. 3 Fijen LM Bork K Cohn DM Current and prospective targets of pharmacologic treatment of hereditary angioedema types 1 and 2. Clin Rev Allergy Immunol. 2021; 61: 66-76 Google Scholar Prophylactic use of an anti-activated factor XII monoclonal antibody, garadacimab, for patients with C1-esterase inhibitor-deficient hereditary angioedema: a randomised, double-blind, placebo-controlled, phase 2 trialGaradacimab 200 mg and 600 mg every 4 weeks significantly reduced the number of monthly attacks versus placebo and was well tolerated during the study. Garadacimab is an efficacious, subcutaneous prophylaxis in patients with HAE-C1-INH and warrants phase 3 evaluation. Full-Text PDF