HAE therapies: past present and future

Hereditary angioedema with reduced C1 inhibitor function (HAE) is an autosomal dominant disease characterized by recurrent episodes of potentially life-threatening angioedema. The pathophysiology of HAE as well as the molecular mechanisms underlying attacks of swelling in HAE have been gradually dissected over the past 50 years [1-3]. These advances have led to a rapidly changing set of therapeutic options for patients with HAE.HAE patients typically begin to swell in childhood, and often suffer increased symptoms about the time of puberty, and continue to experience recurrent attacks of angioedema throughout the remainder of their lives [4]. Attacks of angioedema in HAE can be severe and prolonged, typically lasting 3-5 days before the patient is well again. Abdominal attacks may result in hospitalization and all to often lead to inappropriate intra-abdominal surgery, while oro-pharyngeal-laryngeal attacks can be life-threatening [4-6]. Despite striking advances in medical knowledge, HAE patients continue to die from laryngeal attacks [7,8]. The disease thus imposes an enormous burden on patients as well as their families, often preventing them from leading a productive life.Because of the significant morbidity and mortality associated with HAE, careful management of these patients is essential. The management of HAE required attention to three areas: treatment of acute episodes of angioedema, long-term prophylaxis, and short-term prophylaxis [4,5,9,10]. To help the clinician navigate the changing therapeutic landscape, this article will review the past, current, and future options for treating HAE patients in the United States.Attacks of angioedema in patients with HAE involve subcutaneous tissues (primarily involving extremities, genitalia or the face), the intestine, and the respiratory tract. Attacks typically but not invariably follow a trajectory in which the angioedema increases for 24 hours then slowly decreases over the following 48-72 hours. Importantly,