{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:06:54Z","timestamp":1789049214460,"version":"build-2803163510"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":205,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hereditary angioedema (HAE) is a rare disorder of recurrent swellings of the subcutaneous and\/or mucosal tissues due to defects in the contact system regulation of bradykinin production. The swellings can be disfiguring, cause debilitating abdominal pain, or be fatal with laryngeal obstruction. Over the last decade, there have been immense successes in management of HAE owing to the development of drugs targeting the contact system. This review focuses on management of HAE due to C1-esterase inhibitor (C1-INH) deficiency\/dysfunction, including a global perspective which is under-represented in the literature. HAE with normal C1-INH is outside the scope of this article. The review provides summaries of clinical trials that have led to licensing of new HAE medications and discusses access to these modern drugs from a global perspective.<\/jats:p>","DOI":"10.1093\/cei\/uxag043","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:44:43Z","timestamp":1784893483000},"source":"Crossref","is-referenced-by-count":0,"title":["Hereditary angioedema: on-demand treatment and long-term prophylaxis\u2014a global reality"],"prefix":"10.1093","volume":"220","author":[{"given":"Cassim","family":"Akhoon","sequence":"first","affiliation":[{"name":"Royal Free London NHS Foundation Trust, Department of Immunology , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1299-4415","authenticated-orcid":false,"given":"Sorena","family":"Kiani-Alikhan","sequence":"additional","affiliation":[{"name":"Royal Free London NHS Foundation Trust, Department of Immunology , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"2026091009112859100_uxag043-B1","doi-asserted-by":"crossref","DOI":"10.1016\/j.waojou.2022.100627","article-title":"The international WAO\/EAACI guideline for the management of hereditary angioedema\u2014the 2021 revision and update","volume":"15","author":"Maurer","year":"2022","journal-title":"World Allergy Organ J"},{"key":"2026091009112859100_uxag043-B2","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jaip.2020.08.046","article-title":"US HAEA medical advisory board 2020 guidelines for the management of hereditary angioedema","volume":"9","author":"Busse","year":"2021","journal-title":"J Allergy Clin Immunol Pract"},{"key":"2026091009112859100_uxag043-B3","doi-asserted-by":"crossref","DOI":"10.1371\/annotation\/ab8fe636-8b5b-420e-9cbf-1bef0a19b63f","article-title":"Hereditary angioedema attacks resolve faster and are shorter after early icatibant treatment","volume":"8","author":"Maurer","year":"2013","journal-title":"PLoS One"},{"key":"2026091009112859100_uxag043-B4","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S1081-1206(10)60886-1","article-title":"Fresh frozen plasma for the treatment of hereditary angioedema","volume":"98","author":"Prematta","year":"2007","journal-title":"Ann Allergy Asthma Immunol"},{"key":"2026091009112859100_uxag043-B5","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.jaci.2024.12.1079","article-title":"Interplay between on-demand treatment trials for hereditary angioedema and treatment guidelines","volume":"155","author":"Cohn","year":"2025","journal-title":"J Allergy Clin Immunol"},{"key":"2026091009112859100_uxag043-B6","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s12016-021-08854-5","article-title":"Mitigating disparity in health-care resources between countries for management of hereditary angioedema","volume":"61","author":"Jindal","year":"2021","journal-title":"Clin Rev Allergy Immunol"},{"key":"2026091009112859100_uxag043-B7","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s12016-021-08855-4","article-title":"The global registry for hereditary angioedema due to C1-inhibitor deficiency","volume":"61","author":"Zanichelli","year":"2021","journal-title":"Clin Rev Allergy Immunol"},{"key":"2026091009112859100_uxag043-B8","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jaci.2023.09.039","article-title":"Uncovering the true burden of hereditary angioedema due to C1-inhibitor deficiency: a focus on the Asia-Pacific region","volume":"153","author":"Honda","year":"2024","journal-title":"J Allergy Clin Immunol"},{"key":"2026091009112859100_uxag043-B9","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1056\/NEJMoa0805538","article-title":"Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema","volume":"363","author":"Zuraw","year":"2010","journal-title":"N Engl J Med"},{"key":"2026091009112859100_uxag043-B10","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.jaci.2009.07.017","article-title":"Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks","volume":"124","author":"Craig","year":"2009","journal-title":"J Allergy Clin Immunol"},{"key":"2026091009112859100_uxag043-B11","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1111\/j.1398-9995.2011.02702.x","article-title":"C1 esterase inhibitor concentrate in 1085 hereditary angioedema attacks\u2014final results of the I.M.P.A.C.T.2 study","volume":"66","author":"Craig","year":"2011","journal-title":"Allergy"},{"key":"2026091009112859100_uxag043-B12","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1586\/eci.10.19","article-title":"Summary of the international multicenter prospective angioedema C1-inhibitor trials 1 and 2 (IMPACT1 and 2)","volume":"6","author":"Krassilnikova","year":"2010","journal-title":"Expert Rev Clin Immunol"},{"key":"2026091009112859100_uxag043-B13","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s40261-013-0064-2","article-title":"Immunosafety of recombinant human C1-inhibitor in hereditary angioedema: evaluation of IgE antibodies","volume":"33","author":"Hack","year":"2013","journal-title":"Clin Drug Investig"},{"key":"2026091009112859100_uxag043-B14","author":"European Medicines Agency"},{"key":"2026091009112859100_uxag043-B15","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.jaci.2010.07.021","article-title":"Recombinant human C1-inhibitor for the treatment of acute angioedema attacks in patients with hereditary angioedema","volume":"126","author":"Zuraw","year":"2010","journal-title":"J Allergy Clin Immunol"},{"key":"2026091009112859100_uxag043-B16","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.anai.2013.12.004","article-title":"Recombinant human C1-esterase inhibitor relieves symptoms of hereditary angioedema attacks: phase 3, randomized, placebo-controlled trial","volume":"112","author":"Riedl","year":"2014","journal-title":"Ann Allergy Asthma Immunol"},{"key":"2026091009112859100_uxag043-B17","author":"Electronic Medicines Compendium (EMC)"},{"key":"2026091009112859100_uxag043-B18","author":"Electronic Medicines Compendium (EMC)"},{"key":"2026091009112859100_uxag043-B19","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.anai.2017.01.029","article-title":"Sustained response of recombinant human C1 esterase inhibitor for acute treatment of hereditary angioedema attacks","volume":"118","author":"Bernstein","year":"2017","journal-title":"Ann Allergy Asthma Immunol"},{"key":"2026091009112859100_uxag043-B20","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.anai.2011.08.015","article-title":"Randomized placebo-controlled trial of the bradykinin B2 receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial","volume":"107","author":"Lumry","year":"2011","journal-title":"Ann Allergy Asthma Immunol"},{"key":"2026091009112859100_uxag043-B21","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1056\/NEJMoa0906393","article-title":"Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema","volume":"363","author":"Cicardi","year":"2010","journal-title":"N Engl J Med"},{"key":"2026091009112859100_uxag043-B22","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1056\/NEJMoa0905079","article-title":"Ecallantide for the treatment of acute attacks in hereditary angioedema","volume":"363","author":"Cicardi","year":"2010","journal-title":"N Engl J Med"},{"key":"2026091009112859100_uxag043-B23","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.anai.2010.04.012","article-title":"EDEMA4: a phase 3, double-blind study of subcutaneous ecallantide treatment for acute attacks of hereditary angioedema","volume":"104","author":"Levy","year":"2010","journal-title":"Ann Allergy Asthma Immunol"},{"key":"2026091009112859100_uxag043-B24","author":"U.S. Food and Drug Administration"},{"key":"2026091009112859100_uxag043-B25","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1056\/NEJMoa2314192","article-title":"Oral sebetralstat for on-demand treatment of hereditary angioedema attacks","volume":"391","author":"Riedl","year":"2024","journal-title":"N Engl J Med"},{"key":"2026091009112859100_uxag043-B26","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1001\/archinte.161.20.2417","article-title":"Hereditary angioedema: a broad review for clinicians","volume":"161","author":"Nzeako","year":"2001","journal-title":"Arch Intern Med"},{"key":"2026091009112859100_uxag043-B27","doi-asserted-by":"crossref","DOI":"10.1016\/j.waojou.2019.100049","article-title":"Fresh frozen plasma for on-demand hereditary angioedema treatment in South Africa and Iran","volume":"12","author":"Wentzel","year":"2019","journal-title":"World Allergy Organ J"},{"key":"2026091009112859100_uxag043-B28","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1016\/j.anai.2023.08.122","article-title":"Deucrictibant immediate-release capsule reduces time to end of progression of hereditary angioedema attacks\u2019 manifestations","volume":"131","author":"Riedl","year":"2023","journal-title":"Ann Allergy Asthma Immunol"},{"key":"2026091009112859100_uxag043-B29","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jaci.2024.03.007","article-title":"Deucrictibant for angioedema due to acquired C1-inhibitor deficiency: a randomized-controlled trial","volume":"154","author":"Petersen","year":"2024","journal-title":"J Allergy Clin Immunol"},{"key":"2026091009112859100_uxag043-B30","author":"Pharvaris Netherlands B.V"},{"key":"2026091009112859100_uxag043-B31","author":"Pharvaris Netherlands B.V"},{"key":"2026091009112859100_uxag043-B32","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1056\/NEJMoa1613627","article-title":"Prevention of hereditary angioedema attacks with a subcutaneous C1 inhibitor","volume":"376","author":"Longhurst","year":"2017","journal-title":"N Engl J Med"},{"key":"2026091009112859100_uxag043-B33","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13223-019-0362-1","article-title":"Subcutaneous C1 inhibitor for prevention of attacks of hereditary angioedema: additional outcomes and subgroup analysis of a placebo-controlled randomized study","volume":"15","author":"Li","year":"2019","journal-title":"Allergy Asthma Clin Immunol"},{"key":"2026091009112859100_uxag043-B34","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1001\/jama.2018.16773","article-title":"Effect of lanadelumab compared with placebo on prevention of hereditary angioedema attacks: a randomized clinical trial","volume":"320","author":"Banerji","year":"2018","journal-title":"JAMA"},{"key":"2026091009112859100_uxag043-B35","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1111\/all.15011","article-title":"Long-term prevention of hereditary angioedema attacks with lanadelumab: the HELP OLE study","volume":"77","author":"Banerji","year":"2022","journal-title":"Allergy"},{"key":"2026091009112859100_uxag043-B36","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1111\/all.15620","article-title":"Lanadelumab for the prevention of hereditary angioedema attacks: a real-world UK audit","volume":"78","author":"Dorr","year":"2023","journal-title":"Allergy"},{"key":"2026091009112859100_uxag043-B37","doi-asserted-by":"crossref","first-page":"3882","DOI":"10.1007\/s12325-025-03226-3","article-title":"Sustained effectiveness, tolerability, and safety of long-term prophylaxis with lanadelumab in hereditary angioedema: the prospective, phase 4, noninterventional EMPOWER real-world study","volume":"42","author":"Bernstein","year":"2025","journal-title":"Adv Ther"},{"key":"2026091009112859100_uxag043-B38","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jaci.2020.10.015","article-title":"Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: a randomized, double-blind, placebo-controlled phase 3 trial","volume":"148","author":"Zuraw","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"2026091009112859100_uxag043-B39","author":"Electronic Medicines Compendium (EMC)"},{"key":"2026091009112859100_uxag043-B40","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s12016-024-09006-1","article-title":"Hereditary angioedema attacks in patients receiving long-term prophylaxis: a systematic review","volume":"67","author":"Longhurst","year":"2024","journal-title":"Clin Rev Allergy Immunol"},{"key":"2026091009112859100_uxag043-B41","author":"Canadian Agency for Drugs and Technologies in Health"},{"key":"2026091009112859100_uxag043-B42","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1111\/all.70086","article-title":"National audit of long-term real-world outcomes of berotralstat use in UK patients with hereditary angioedema","volume":"81","author":"Elbashir","year":"2026","journal-title":"Allergy"},{"key":"2026091009112859100_uxag043-B43","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/S0140-6736(23)00350-1","article-title":"Efficacy and safety of garadacimab, a factor XIIa inhibitor for hereditary angioedema prevention (VANGUARD): a global, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial","volume":"401","author":"Craig","year":"2023","journal-title":"Lancet"},{"key":"2026091009112859100_uxag043-B44","author":"U.S. Food and Drug Administration"},{"key":"2026091009112859100_uxag043-B45","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1056\/NEJMoa2402478","article-title":"Efficacy and safety of donidalorsen for hereditary angioedema","volume":"391","author":"Riedl","year":"2024","journal-title":"N Engl J Med"},{"key":"2026091009112859100_uxag043-B46","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2011-000524","article-title":"Long-term prophylaxis in hereditary angio-oedema: a systematic review","volume":"2","author":"Costantino","year":"2012","journal-title":"BMJ Open"},{"key":"2026091009112859100_uxag043-B47","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1056\/NEJM197612232952602","article-title":"Treatment of hereditary angioedema with danazol: reversal of clinical and biochemical abnormalities","volume":"295","author":"Gelfand","year":"1976","journal-title":"N Engl J Med"},{"key":"2026091009112859100_uxag043-B48","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1056\/NEJM197208312870907","article-title":"Tranexamic acid therapy in hereditary angioneurotic edema","volume":"287","author":"Sheffer","year":"1972","journal-title":"N Engl J Med"},{"key":"2026091009112859100_uxag043-B49","author":"Pharvaris Netherlands B.V"},{"key":"2026091009112859100_uxag043-B50","author":"Pharvaris Netherlands B.V"},{"key":"2026091009112859100_uxag043-B51","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.anai.2025.03.016","article-title":"Safety and pharmacokinetics of long-acting plasma kallikrein inhibitor navenibart (STAR-0215) in healthy adults","volume":"135","author":"Lumry","year":"2025","journal-title":"Ann Allergy Asthma Immunol"},{"key":"2026091009112859100_uxag043-B52","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1056\/NEJMoa2309149","article-title":"CRISPR-Cas9 in vivo gene editing of KLKB1 for hereditary angioedema","volume":"390","author":"Longhurst","year":"2024","journal-title":"N Engl J Med"},{"key":"2026091009112859100_uxag043-B53","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jaci.2024.06.011","article-title":"An LNP-CRISPR gene editing drug demonstrates efficacy and safety in patients with hereditary angioedema following in vivo administration","volume":"154","author":"Pardi","year":"2024","journal-title":"J Allergy Clin Immunol"},{"key":"2026091009112859100_uxag043-B54","doi-asserted-by":"crossref","first-page":"10","DOI":"10.2500\/aap.2020.41.190005","article-title":"Long-term safety outcomes of prekallikrein (Fletcher factor) deficiency: a systematic literature review of case reports","volume":"41","author":"Girolami","year":"2020","journal-title":"Allergy Asthma Proc"},{"key":"2026091009112859100_uxag043-B55","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1111\/jth.14805","article-title":"Severe plasma prekallikrein deficiency: clinical characteristics, novel KLKB1 mutations, and estimated prevalence","volume":"18","author":"Barco","year":"2020","journal-title":"J Thromb Haemost"},{"key":"2026091009112859100_uxag043-B56","doi-asserted-by":"crossref","first-page":"2870","DOI":"10.1016\/j.jaip.2024.06.041","article-title":"Disparities in geography and race in hereditary angioedema: analysis of 64 trials and 4354 patients","volume":"12","author":"Mak","year":"2024","journal-title":"J Allergy Clin Immunol Pract"},{"key":"2026091009112859100_uxag043-B57","article-title":"Equitable access to clinical trials: how do we achieve it?","volume":"43","author":"Acu\u00f1a-Villaordu\u00f1a","year":"2023","journal-title":"Am Soc Clin Oncol Educ Book"},{"key":"2026091009112859100_uxag043-B58","author":"WMA"},{"key":"2026091009112859100_uxag043-B59","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2021.7075","article-title":"Evaluation of drug trials in high-, middle-, and low-income countries and local commercial availability of newly approved drugs","volume":"4","author":"Miller","year":"2021","journal-title":"JAMA Netw Open"},{"key":"2026091009112859100_uxag043-B60","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1001\/jamainternmed.2025.6060","article-title":"Physical accessibility of medicines in countries hosting trials for FDA approvals","volume":"186","author":"Lee","year":"2026","journal-title":"JAMA Intern Med"},{"key":"2026091009112859100_uxag043-B61","article-title":"Challenges of globalization of cancer drug trials- recruitment in LMICs, approval in HICs","volume":"7","author":"Gyawali","year":"2022","journal-title":"Lancet Reg Health\u2014Am"},{"key":"2026091009112859100_uxag043-B62","article-title":"Clinical validity of dried blood spot assay for the measurement of functional C1 inhibitor in angioedema due to C1 inhibitor deficiency","volume":"4","author":"Bernstein","year":"2025","journal-title":"J Allergy Clin Immunol Glob"},{"key":"2026091009112859100_uxag043-B63","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1710-1492-9-29","article-title":"Hereditary angioedema with C1 inhibitor deficiency: delay in diagnosis in Europe","volume":"9","author":"Zanichelli","year":"2013","journal-title":"Allergy Asthma Clin Immunol"},{"key":"2026091009112859100_uxag043-B64","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/cei.12159","article-title":"A UK national audit of hereditary and acquired angioedema","volume":"175","author":"Jolles","year":"2013","journal-title":"Clin Exp Immunol"},{"key":"2026091009112859100_uxag043-B65","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1111\/cea.70284","article-title":"Unearthing hereditary angioedema in India-epidemiology from Chandigarh and Reasi, India","volume":"56","author":"Jindal","year":"2026","journal-title":"Clin Exp Allergy J Br Soc Allergy Clin Immunol"},{"key":"2026091009112859100_uxag043-B66","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1097\/00005792-199207000-00003","article-title":"Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients","volume":"71","author":"Agostoni","year":"1992","journal-title":"Medicine (Baltimore)"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cei\/advance-article-pdf\/doi\/10.1093\/cei\/uxag043\/70017115\/uxag043.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/220\/1\/uxag043\/70017115\/uxag043.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/220\/1\/uxag043\/70017115\/uxag043.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:11:38Z","timestamp":1789045898000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/doi\/10.1093\/cei\/uxag043\/8741804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":66,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,6]]}},"URL":"https:\/\/doi.org\/10.1093\/cei\/uxag043","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"uxag043"}}