{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:48:03Z","timestamp":1789170483638,"version":"build-2803163510"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014387","name":"ACADIA Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014387","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Develop Med Child Neuro"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To describe the real\u2010world effects of trofinetide in individuals with Rett syndrome (RTT) using the 18\u2010month follow\u2010up analysis of the LOTUS study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Caregivers of any patients who were prescribed trofinetide under routine clinical care were eligible to participate. Assessments included the Behavioral Improvement Questionnaire (BIQ), the Quality of Life Inventory\u2010Disability (QI\u2010Disability) questionnaire, the Gastrointestinal Health Questionnaire, and safety monitoring. Data are reported to 12\u2009months since the initiation of trofinetide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 227 caregivers participated in this follow\u2010up. The median trofinetide dose at week 1 was 36.0% of the target dose and increased to over 80% by week 10 onwards; 55.2% of patients took the full trofinetide recommended daily dose. Caregivers (71%\u201390%) reported behavioral improvements across months 1 to 12 with the BIQ, including non\u2010verbal communication (48%\u201371%), alertness (44%\u201370%), and social interaction and connectedness (33%\u201358%). The median QI\u2010Disability total score change from baseline ranged from 4.7 to 4.6 in months 1 to 12. The incidence of diarrhea varied from weeks 1 to 12 (23%\u201350%) and months 4 to 12 (26%\u201338%); most reports of diarrhea were contained inside the patient's diaper. Safety reports were consistent with previous trofinetide clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Results from the LOTUS study show improvements in the symptoms of RTT, with early insights into managing gastrointestinal symptoms in the context of real\u2010world patient care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dmcn.16482","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T04:13:44Z","timestamp":1757650424000},"page":"407-417","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Real\u2010world benefits and tolerability of trofinetide for the treatment of Rett syndrome: The LOTUS study"],"prefix":"10.1111","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1896-0147","authenticated-orcid":false,"given":"Louise","family":"Cosand","sequence":"first","affiliation":[{"name":"Acadia Pharmaceuticals  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haya","family":"Mayman","sequence":"additional","affiliation":[{"name":"Acadia Pharmaceuticals  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7358-9037","authenticated-orcid":false,"given":"Jenny","family":"Downs","sequence":"additional","affiliation":[{"name":"The Kids Research Institute Australia, The Centre for Child Health Research, University of Western Australia  Perth WA Australia"},{"name":"Curtin School of Allied Health, Faculty of Health Sciences, Curtin University  Perth WA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Abler","sequence":"additional","affiliation":[{"name":"Acadia Pharmaceuticals  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13643-023-02169-6"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32707"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22124"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14081607"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjpo-2020-000731"},{"key":"e_1_2_8_7_1","volume-title":"DAYBUE (trofinetide) [package insert]","author":"Pharmaceuticals Acadia","year":"2024"},{"key":"e_1_2_8_8_1","unstructured":"Acadia Pharmaceuticals Inc.DAYBUE Canadian Product Monograph[cited 2025 Aug 7]. Available from:https:\/\/acadia.com\/en\u2010ca\/pdf\/our\u2010medicine\/health\u2010canada\u2010daybue\u2010product\u2010monograph\u2010october\u201011\u20102024.pdf"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02398-1"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2024.05.018"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2024.06.007"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000204788"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2023.11.005"},{"key":"e_1_2_8_14_1","unstructured":"International Rett Syndrome Foundation Rett Syndrome Research Trust. Voice of the patient report: Rett syndrome externally\u2010led patient\u2010focused drug development meeting.https:\/\/www.rettsyndrome.org\/wp\u2010content\/uploads\/2022_Rett\u2010Syndrome\u2010Voice\u2010of\u2010the\u2010Patient\u2010Report.pdf(accessed 11 November 2024)"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-023-09502-z"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/1469-7610.00236"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2020-107120"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/DBP.0000000000000815"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11136-018-2057-3"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/09638288.2019.1610801"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/07434618.2018.1462848"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000205214"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678707.2023.2217328"}],"container-title":["Developmental Medicine &amp; Child Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dmcn.16482","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dmcn.16482","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dmcn.16482","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:01:55Z","timestamp":1772996515000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/dmcn.16482"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,11]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1111\/dmcn.16482"],"URL":"https:\/\/doi.org\/10.1111\/dmcn.16482","archive":["Portico"],"relation":{},"ISSN":["0012-1622","1469-8749"],"issn-type":[{"value":"0012-1622","type":"print"},{"value":"1469-8749","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,11]]},"assertion":[{"value":"2024-12-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}