{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:42:06Z","timestamp":1791013326430,"version":"4.1.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"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. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rett syndrome (RTT) is a rare, progressive MECP2-related neurodevelopmental disorder with substantial lifelong morbidity that persists into adulthood. Although survival has improved, adults often experience evolving multisystem complications and fragmented transition care. Trofinetide (TROF) is approved for ages \u22652\u202fyears old, yet data on adults with RTT in the real-world setting remains limited; this study evaluated demographics and characteristics of adults &amp;gt;20\u202fyears of age who are treated vs. untreated with TROF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective analysis of individuals with RTT diagnosis (ICD-10-CM: F84.2) from a linked medical claims and specialty pharmacy database from 01\/01\/2021 to 09\/30\/2024 was conducted. RTT individuals were categorized into two groups based on treatment status: treated group (index date: 1st TROF prescription (RX) 04\/01\/2023 to 03\/31\/2024) and untreated group (index date: assigned date using a risk set sampling method). Individuals who were \u226420\u202fyears of age at index date or had diagnosis for brain trauma or cerebrovascular disease prior to RTT diagnosis were excluded. RTT individuals were required to have continuous enrollment for \u22656\u202fmonths pre-index and post-index. Demographics and clinical characteristics were assessed during pre-index among the treated and untreated groups. Continuous variables were summarized as means and SD; categorical variables as counts and percentages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There were 1,820 adult RTT individuals (&amp;gt;20\u202fyear old) eligible for the analysis: treated group (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f290 [15.9%]) and untreated group (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f1,530 [84.1%]). Mean age (SD) at index date was 30.9 (9.9) years (treated group) vs. 33.5 (10.0) years (untreated); and 5.5% vs. 6.7% were males in the treated vs. untreated groups, respectively. Treated group had higher rates of differential diagnoses, but similar rates of baseline comorbidities among both. Treated group also had higher rates of RTT related clinical features vs. untreated group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this real-world analysis, only 16% of eligible adult RTT individuals were initiated on TROF, while 84% remain untreated. There is a high unmet need for adult individuals with RTT to initiate treatment with TROF. Treated group had higher rates of RTT related clinical features and differential diagnoses; however, the observation that TROF is being used in adults with greater to similar baseline complexity compared to untreated may provide reassurance for prescribers to consider TROF in adults who were untreated.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1856312","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T04:25:59Z","timestamp":1785126359000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Characteristics of adult individuals with Rett syndrome treated or untreated with trofinetide in the United States"],"prefix":"10.3389","volume":"17","author":[{"given":"Nazia","family":"Rashid","sequence":"first","affiliation":[{"name":"Medical Affairs, Acadia Pharmaceuticals Inc","place":["San Diego, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa","family":"Peckham","sequence":"additional","affiliation":[{"name":"Medical Affairs, Acadia Pharmaceuticals Inc","place":["San Diego, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod Kumar","family":"Yakkala","sequence":"additional","affiliation":[{"name":"Anlitiks Inc","place":["Windermere, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Cosand","sequence":"additional","affiliation":[{"name":"Medical Affairs, Acadia Pharmaceuticals Inc","place":["San Diego, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krithika","family":"Rajagopalan","sequence":"additional","affiliation":[{"name":"Anlitiks Inc","place":["Windermere, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/13810","article-title":"Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2","volume":"23","author":"Amir","year":"1999","journal-title":"Nat Genet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1002\/ana.22124","article-title":"Rett syndrome: revised diagnostic criteria and nomenclature","volume":"68","author":"Neul","year":"2010","journal-title":"Ann Neurol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"8277","DOI":"10.3390\/ijms26178277","article-title":"MECP2 dysfunction in Rett syndrome: molecular mechanisms, multisystem pathology, and emerging therapeutic strategies","volume":"26","author":"Choi","year":"2025","journal-title":"Int J Mol 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