{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T16:32:09Z","timestamp":1754152329518,"version":"3.41.2"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hereditary angioedema (HAE) is a genetic disorder characterized by episodic subcutaneous and submucosal swelling. Patient-reported outcome measures (PROMs) are recommended for routine clinical assessment by international guidelines and are used as secondary outcome measures in pivotal clinical trials for novel investigational drugs. The Angioedema Control Test (AECT) and Hereditary Angioedema Activity Score (HAE-AS) are validated tools designed to aid in HAE patient assessment, but the extent to which they measure different disease outcomes is unclear. The aim of this study was to examine how these measures correlate and inform clinical practice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a retrospective study of patients with HAE types 1 and 2 at the Edmonton Angioedema Center of Reference and Excellence. AECT and HAE-AS scores were obtained from patient-completed questionnaires during routine visits. Multiple linear regression was used to examine the association between HAE-AS and AECT scores with age, sex, and long-term prophylaxis (LTP) status as predictors. Receiver operating characteristic (ROC) analysis was used to determine the optimal HAE-AS score cutoff that predicts poor disease control as determined by the AECT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were 25 participants included with a mean age of 39.4 years (SD = 13.7), 72% of whom were female. Most had HAE Type 1 (76%) and 52% were receiving LTP. SC C1-inhibitor therapy was the most common LTP (36%). Most had well managed disease with a median AECT score of 11.88 (range: 5-16) and HAE-AS of 5.84 (range: 0-13). A statistically significant but weak negative correlation was found between AECT and HAE-AS (\u03b2=\u22120.67, p=0.002). ROC analysis showed that an HAE-AS score &amp;gt;5 had a sensitivity of 100% and specificity of 61% for poor disease control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The AECT and HAE-AS instruments are weakly correlated, indicating that they provide related but distinct information to the practicing clinician. Using both AECT and HAE-AS in clinical practice can thus provide a more comprehensive patient evaluation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1631448","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T04:10:21Z","timestamp":1753157421000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Disease control and disease activity in hereditary angioedema: two sides of the same coin?"],"prefix":"10.3389","volume":"16","author":[{"given":"Behzad","family":"Heibati","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Borle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Ritchie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adil","family":"Adatia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"100627","DOI":"10.1016\/j.waojou.2022.100627","article-title":"The international WAO\/EAACI guideline for the management of hereditary angioedema\u2013The 2021 revision and update","volume":"15","author":"Maurer","year":"2022","journal-title":"World Allergy Organ J"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/all.15214","article-title":"The international WAO\/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update","volume":"77","author":"Maurer","year":"2022","journal-title":"Allergy"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-021-08835-8","article-title":"Pathophysiology of hereditary angioedema (HAE) beyond the SERPING1 gene","volume":"60","author":"Sharma","year":"2021","journal-title":"Clin Rev Allergy Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.therap.2020.02.011","article-title":"Update on bradykinin-mediated angioedema in 2020","volume":"75","author":"Lepelley","year":"2020","journal-title":"Therapies"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2013.06.004","article-title":"Hereditary angioedema with normal C1-INH (HAE type III)","volume":"1","author":"Riedl","year":"2013","journal-title":"J Allergy Clin Immunology: In Practice"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/falgy.2022.835503","article-title":"SERPING1 variants and C1-INH biological function: a close relationship with C1-INH-HAE","volume":"3","author":"Drouet","year":"2022","journal-title":"Front Allergy"},{"key":"B7","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s13223-019-0376-8","article-title":"The international\/Canadian hereditary angioedema guideline","volume":"15","author":"Betschel","year":"2019","journal-title":"Allergy Asthma Clin Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/all.14293","article-title":"Definition, aims, and implementation of GA(2) LEN\/HAEi Angioedema Centers of Reference and Excellence","volume":"75","author":"Maurer","year":"2020","journal-title":"Allergy"},{"key":"B9","doi-asserted-by":"publisher","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":"B10","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.1016\/j.jaip.2021.03.057","article-title":"Randomized trial of the efficacy and safety of berotralstat (BCX7353) as an oral prophylactic therapy for hereditary angioedema: results of APeX-2 through 48 weeks (Part 2)","volume":"9","author":"Wedner","year":"2021","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B11","doi-asserted-by":"publisher","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":"B12","doi-asserted-by":"publisher","first-page":"e12295","DOI":"10.1002\/clt2.12295","article-title":"Sensitivity to change and minimal clinically important difference of the angioedema control test","volume":"13","author":"Fijen","year":"2023","journal-title":"Clin Transl Allergy"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/all.12007","article-title":"Development and construct validation of the angioedema quality of life questionnaire","volume":"67","author":"Weller","year":"2012","journal-title":"Allergy"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/all.14144","article-title":"Development of the Angioedema Control Test-A patient-reported outcome measure that assesses disease control in patients with recurrent angioedema","volume":"75","author":"Weller","year":"2020","journal-title":"Allergy"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2021.02.026","article-title":"How to measure disease activity, impact, and control in patients with recurrent wheals, angioedema, or both","volume":"9","author":"Katelaris","year":"2021","journal-title":"J Allergy Clin Immunology: In Practice"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2050","DOI":"10.1016\/j.jaip.2020.02.038","article-title":"Validation of the Angioedema Control Test (AECT)\u2014a patient-reported outcome instrument for assessing angioedema control","volume":"8","author":"Weller","year":"2020","journal-title":"J Allergy Clin Immunology: In\u00a0Practice"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/all.12900","article-title":"The Angioedema Quality of Life Questionnaire (AE-QoL)\u2013assessment of sensitivity to change and minimal clinically important difference","volume":"71","author":"Weller","year":"2016","journal-title":"Allergy"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2015-000202","article-title":"Systematic review of patient-reported outcome measures (PROMs) for assessing disease activity in rheumatoid arthritis","volume":"2","author":"Hendrikx","year":"2016","journal-title":"RMD Open"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2017.00212","article-title":"Disease severity, activity, impact, and control and how to assess them in patients with hereditary angioedema","volume":"4","author":"Bygum","year":"2017","journal-title":"Front Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.18176\/jiaci.0479","article-title":"HAE-AS: A specific disease activity scale for hereditary angioedema with C1-inhibitor deficiency","volume":"31","author":"Forjaz","year":"2021","journal-title":"J Investig Allergol Clin Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13223-021-00537-2","article-title":"Assessment and management of disease burden and quality of life in patients with hereditary angioedema: a consensus report","volume":"17","author":"Bork","year":"2021","journal-title":"Allergy Asthma Clin Immunol"},{"key":"B22","doi-asserted-by":"publisher","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":"New Engl J Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1339421","article-title":"Berotralstat in hereditary angioedema due to C1 inhibitor deficiency: first real-world evidence from a Canadian center","volume":"15","author":"Srinivasan","year":"2024","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1413547","article-title":"Centralized care model for hereditary angioedema overcomes geographical barriers","volume":"15","author":"Holmes","year":"2024","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(1950)3:1<32::AID-CNCR2820030106>3.0.CO;2-3","article-title":"Index for rating diagnostic tests","volume":"3","author":"Youden","year":"1950","journal-title":"Cancer"},{"key":"B26","doi-asserted-by":"publisher","first-page":"100758","DOI":"10.1016\/j.waojou.2023.100758","article-title":"A narrative review of recent literature of the quality of life in hereditary angioedema patients","volume":"16","author":"Chong-Neto","year":"2023","journal-title":"World Allergy Organ J"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2020.02.018","article-title":"Patient-reported burden of hereditary angioedema: findings from a patient survey in the United States","volume":"124","author":"Banerji","year":"2020","journal-title":"Ann Allergy Asthma Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/all.14680","article-title":"Impact of lanadelumab on health-related quality of life in patients with hereditary angioedema in the HELP study","volume":"76","author":"Lumry","year":"2021","journal-title":"Allergy"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2023.04.017","article-title":"Hereditary angioedema: a review of the current and evolving treatment landscape","volume":"11","author":"Betschel","year":"2023","journal-title":"J Allergy Clin Immunology: In\u00a0Practice"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2005.09.064","article-title":"Hereditary angioedema: new findings concerning symptoms, affected organs, and course","volume":"119","author":"Bork","year":"2006","journal-title":"Am J Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2013.08.019","article-title":"The burden of illness in patients with hereditary angioedema","volume":"111","author":"Banerji","year":"2013","journal-title":"Ann Allergy Asthma Immunol"},{"key":"B32","doi-asserted-by":"publisher","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":"B33","doi-asserted-by":"publisher","first-page":"2050","DOI":"10.1016\/j.jaip.2020.02.038","article-title":"Validation of the angioedema control test (AECT)-A patient-reported outcome instrument for assessing angioedema control","volume":"8","author":"Weller","year":"2020","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00350-1","article-title":"Efficacy\u00a0and\u00a0safety 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"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1631448\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T04:10:23Z","timestamp":1753157423000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1631448\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,22]]},"references-count":34,"alternative-id":["10.3389\/fimmu.2025.1631448"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1631448","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2025,7,22]]},"article-number":"1631448"}}