{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T19:07:36Z","timestamp":1792868856689,"version":"4.5.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T00:00:00Z","timestamp":1752278400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T00:00:00Z","timestamp":1752278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Activated phosphoinositide 3-kinase delta syndrome (APDS) is a rare genetic disease associated with heterogeneous manifestations, including recurrent infections, lymphoproliferation, and autoimmunity. This analysis sought to estimate the mean annual direct medical costs of manifestations associated with APDS. A burden-of-illness cost calculator was developed based on survey responses from the US clinical experts, published evidence, and the US cost sources (2023). Results from the survey provided estimates of mean annual prevalence of various manifestations associated with APDS and the mean number of times patients experienced recurrent manifestations in a year. In the base case analysis, the annual mean cost of manifestations associated with APDS per patient in the US was estimated to be $116,387 (range, $10,711\u2013$417,455) with gastrointestinal-, infection-, and hematology-related manifestations being the largest contributing factors. The weighted average scenario analysis resulted in similar estimates of mean annual manifestation costs as the base case analysis. To our knowledge, our study is the first to provide estimates of annual prevalence of manifestations associated with APDS and to estimate the annual direct medical costs for patients with APDS in the US. The high mean annual cost associated with APDS contributes to the economic burden of patients and health care payers. Patients with APDS often require off-label, symptomatic treatments for various manifestations that do not target the root cause of the disorder. These treatments are associated with high costs that may not control symptoms. This analysis provides valuable support for discussions about resource utilization and the economic burden of APDS.<\/jats:p>","DOI":"10.1007\/s10238-025-01773-1","type":"journal-article","created":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T15:58:04Z","timestamp":1752335884000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Estimated annual direct medical costs of manifestations among patients with activated phosphoinositide 3-kinase delta syndrome"],"prefix":"10.1007","volume":"25","author":[{"given":"Nicholas L.","family":"Hartog","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eveline Y.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas L.","family":"Rider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Hartline","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurabh","family":"Aggarwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8294-5002","authenticated-orcid":false,"given":"Amanda","family":"Harrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,12]]},"reference":[{"key":"1773_CR1","doi-asserted-by":"publisher","first-page":"1208567","DOI":"10.3389\/fimmu.2023.1208567","volume":"14","author":"S Vanselow","year":"2023","unstructured":"Vanselow S, Wahn V, Schuetz C. Activated PI3K\u03b4 syndrome\u2014reviewing challenges in diagnosis and treatment. Front Immunol. 2023;14:1208567.","journal-title":"Front Immunol"},{"issue":"4","key":"1773_CR2","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1016\/j.jaci.2023.06.015","volume":"152","author":"ME Maccari","year":"2023","unstructured":"Maccari ME, Wolkewitz M, Schwab C, Lorenzini T, Leiding JW, Aladjdi N, et al. Activated phosphoinositide 3-kinase \u03b4 syndrome: update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity. J Allergy Clin Immunol. 2023;152(4):984-96.e10.","journal-title":"J Allergy Clin Immunol"},{"key":"1773_CR3","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.3389\/fimmu.2018.02043","volume":"9","author":"TI Coulter","year":"2018","unstructured":"Coulter TI, Cant AJ. The treatment of activated PI3K\u03b4 syndrome. 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J Allergy Clin Immunol Pract. 2024;12(1):69\u201378.","journal-title":"J Allergy Clin Immunol Pract"},{"issue":"9","key":"1773_CR6","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1182\/blood.2019002072","volume":"135","author":"A Durandy","year":"2020","unstructured":"Durandy A, Kracker S. Increased activation of PI3 kinase-\u03b4 predisposes to B-cell lymphoma. Blood. 2020;135(9):638\u201343.","journal-title":"Blood"},{"issue":"1","key":"1773_CR7","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1186\/s13023-025-03734-z","volume":"20","author":"M Mahendran","year":"2025","unstructured":"Mahendran M, Upton JEM, Ramasubramanian R, Memmott HL, Germain G, B\u00fcsch K, et al. Overall survival among patients with activated phosphoinositide 3-kinase delta syndrome (APDS). 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Hartog reports receipt of consulting fees from Pharming Healthcare, Inc., and Amgen and speaker fees from X4 Pharmaceuticals, ADMA Biologics, Inc., Amgen, Takeda, and Pharming Healthcare, Inc. Eveline Y. Wu reports receipt of consulting fees and payment for speaker bureaus from Pharming Healthcare, Inc. Nicholas L. Rider reports receiving grants or contracts unrelated to this work from the National Institutes of Health\/National Institute of Allergy and Infectious Diseases, Centers for Disease Control and Prevention via the Jeffrey Modell Foundation, and Takeda; receiving royalties or licenses from Wolters Kluwer; receiving consulting and speaker fees for serving on advisory boards from Pharming Healthcare, Inc., Takeda, X4 Pharmaceuticals, and Grifols and for serving on a steering committee for Pharming Healthcare, Inc.; receiving support for attending meetings from Takeda, Pharming Healthcare, Inc., and Grifols; and for support in attending meetings and\/or travel (as a speaker) for Takeda and Grifols. Yang Meng is an employee of Lumanity, which received consulting fees from Pharming Healthcare, Inc. Saurabh Aggarwal is an employee of NOVEL Health Strategies and has received consulting fees from Pharming Healthcare, Inc. Brian Hartline, Philippe Adams, and Amanda Harrington are employees of Pharming Healthcare, Inc.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"This article is based on clinical expert survey data and publicly available cost information and does not contain any new studies with human participants or animals performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"246"}}