Hereditary Angioedema: The Economics of Treatment of an Orphan Disease

Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is characterized by relapsing skin swellings, abdominal pain attacks, and, less frequently, potentially life-threatening laryngeal attacks. This study determined the mortality of patients with and without the diagnosis of HAE-C1-INH and analyzed fatal laryngeal attacks. A cohort of 728 patients from 182 families with HAE-C1-INH was evaluated for death cases by analyzing pedigrees. Detailed information on fatal laryngeal attacks in 36 patients was obtained by questioning relatives and treating physicians. Of the 214 patients who had died, 70 asphyxiated during a laryngeal attack. Mortality by asphyxiation was higher in patients with undiagnosed HAE-C1-INH (63 cases) than in patients with diagnosed HAE-C1-INH (7 cases). The lifespan of asphyxiated patients with undiagnosed HAE-C1-INH was on average ∼31 years shorter than patients with undiagnosed HAE-C1-INH who died of other causes. Three phases were distinguished in the fatal laryngeal attacks. Phase 1, the predyspnea phase, lasted on average for 3.7 ± 3.2 hours (range, 0-11 hours). Phase 2, the dyspnea phase, lasted on average for 41 ± 49 minutes (range, 2 minutes to 4 hours). Phase 3, the loss of consciousness phase, lasted on average for 8.9 ± 5.1 minutes (range, 2-20 minutes). The high mortality in patients with undiagnosed HAE-C1-INH underscores the need to identify these patients and diagnose their condition. The analysis of fatal laryngeal attacks gives further insight into their course, thus helping to avoid fatalities in the future. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Objective To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010). Methods The Canadian Hereditary Angioedema Network (CHAEN)/Réseau Canadien d'angioédème héréditaire (RCAH) http://www.haecanada.com and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring) held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus approach. The Consensus document was reviewed at the meeting and then circulated for review. Results This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference. Conclusions Consensus approach is only an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches including quality of life and cost benefit analyses, followed by large head-to-head clinical trials and then evidence-based guidelines and standards for HAE disease management.