{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:48:02Z","timestamp":1789170482764,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":["Annals of the Child Neurology Society"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Trofinetide is the first approved treatment for Rett syndrome (RTT) in the United States and Canada. Trofinetide improved the core symptoms of RTT in clinical trials, and real\u2010world evidence supports the findings of clinical trials. As RTT experts in the United States have now gained nearly 3 years of real\u2010world experience with trofinetide, a modified Delphi process was conducted in the United States to establish consensus recommendations for the practical use of trofinetide in the treatment of RTT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A multidisciplinary steering group of five trofinetide\u2010experienced RTT experts practicing at an International Rett Syndrome Foundation (IRSF)\u2010designated center of excellence convened and developed 72 consensus statements across six domains: first\u2010line use, pre\u2010treatment assessment, initiation, benefit evaluation, tolerability management, and discontinuation strategies. The statements were then assigned a 4\u2010point Likert scale for testing via email by the Delphi panel identified by the steering group. Consensus was reached for individual statements if they met the pre\u2010specified consensus threshold of \u2265\u200975% agreement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two rounds of assessments were completed by 25 respondents in each round, resulting in agreement\u2009\u2265\u200975% being reached across the final statement set. The consensus supports trofinetide as the standard of care for eligible patients with early initiation and an individualized approach to titration to maximize efficacy and tolerability. The panel reflected the steering group's view that trofinetide is efficacious. While side effects can emerge with trofinetide, they are manageable in most cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Recommendations highlight a flexible, patient\u2010centered approach to trofinetide use to optimize efficacy while addressing tolerability challenges and supporting adherence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns3.70062","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:09:08Z","timestamp":1773004148000},"page":"38-51","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Expert Consensus on Real\u2010World Use of Trofinetide for Rett Syndrome Using a Modified Delphi Method"],"prefix":"10.1002","volume":"4","author":[{"given":"Erin O'Connor","family":"Prange","sequence":"first","affiliation":[{"name":"Division of Neurology Children's Hospital of Philadelphia Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Beisang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gillette Children's Specialty Healthcare Saint Paul Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5788-0270","authenticated-orcid":false,"given":"Davut","family":"Pehlivan","sequence":"additional","affiliation":[{"name":"Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics Baylor College of Medicine Houston Texas USA"},{"name":"Blue Bird Circle Rett Center, Texas Children's Hospital Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Suter","sequence":"additional","affiliation":[{"name":"Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics Baylor College of Medicine Houston Texas USA"},{"name":"Blue Bird Circle Rett Center, Texas Children's Hospital Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Schleifer","sequence":"additional","affiliation":[{"name":"Department of Neurology Nicklaus Children's Hospital Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22124"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1229553"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1108\/mi.2016.6302"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.149"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-015-9104-y"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jar.13188"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph16010041"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2006.252"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-024-01106-y"},{"key":"e_1_2_11_12_1","unstructured":"H.Leonard K.Wong D.Doshi andJ.Downs \u201cRett Syndrome Behaviour Questionnaire (RSBQ): The Natural History of RSBQ Scores \u201d presented at the 9th World Rett Syndrome Congress; October 2\u20135 2024; Gold Coast QLD Australia."},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02398-1"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.5582\/irdr.2023.01060"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.07.002"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2024.05.018"},{"key":"e_1_2_11_17_1","first-page":"1275","volume-title":"Med (New York, NY)","author":"Percy A. K.","year":"2024"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2024.12.012"},{"key":"e_1_2_11_19_1","unstructured":"DAYBUE (trofinetide) \u201cHighlights of Prescribing Information \u201d accessed November 6 2025 https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/217026s001s003lbl.pdf."},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.16482"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/23995270.2024.2375191"},{"key":"e_1_2_11_22_1","unstructured":"D. N.Lieberman C.Correa A.Beisang et al. \u201cReal\u2010World Use of Trofinetide: A Survey of Dosing Strategies from US Rett Syndrome Centers of Excellence \u201d presented at the American Epilepsy Society (AES) Annual Meeting; December 6\u201310 2024; Los Angeles CA."},{"key":"e_1_2_11_23_1","unstructured":"E.Prange S. M.Standridge C.Smith\u2010Hicks et al. \u201cReal\u2010World Use of Trofinetide: A Survey of Tolerability from US Rett Syndrome Centers of Excellence \u201d presented at the American Epilepsy Society (AES) Annual Meeting; December 6\u201310 2024; Los Angeles CA."},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2013.12.002"},{"key":"e_1_2_11_25_1","unstructured":"Acadia Pharmaceuticals Inc. \u201cDAYBUE Canadian Product Monograph \u201d accessed November 6 2025 https:\/\/pdf.hres.ca\/dpd_pm\/00077391.PDF."},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjpo-2020-000731"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1866-1955-6-20"},{"key":"e_1_2_11_28_1","unstructured":"L.Cosand V.Abler R.Ryther andA.Beisang \u201cReal\u2010World Trofinetide Dosing for Rett Syndrome: The LOTUS Study \u201d presented at the 53rd Child Neurology Society (CNS) Annual Meeting; November 11\u201314 2024; San Diego CA USA."},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/23995270.2025.2532358"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e31824b6159"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2008.11.018"},{"key":"e_1_2_11_32_1","unstructured":"E.O'Connor Prange D.Fleysh K.Reddy H.Dubbs andE.Marsh \u201cReal\u2010World Impact of Trofinetide for Treatment of Rett Syndrome and OtherMECP2\u2010Related Diagnoses \u201d presented at the 2025 IRSF Rett Syndrome Scientific Meeting; June 9\u201311 2025; Boston MA USA."},{"key":"e_1_2_11_33_1","unstructured":"A.Peckham A.Ananth L.Robinson C.Zhu R.Revankar andL.Cosand \u201cTime to Response to Trofinetide in Patients With Rett Syndrome: Results From Trofinetide Clinical Trials \u201d presented at the 2025 IRSF Rett Syndrome Scientific Meeting; June 9\u201311 2025; Boston MA USA."},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678707.2023.2217328"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-024-03506-9"},{"key":"e_1_2_11_36_1","unstructured":"H.Levine K.Urbanik S.Kyle andV.Prakash \u201cCompatibility of Trofinetide with Ketogenic Diets in Patients With Rett Syndrome: Case Reports \u201d presented at the American Epilepsy Society (AES) 2025 Annual Meeting; December 5\u20138 2025; Atlanta GA USA."}],"container-title":["Annals of the Child Neurology Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns3.70062","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cns3.70062","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns3.70062","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:41:40Z","timestamp":1773765700000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cns3.70062"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/cns3.70062"],"URL":"https:\/\/doi.org\/10.1002\/cns3.70062","archive":["Portico"],"relation":{},"ISSN":["2831-3267","2831-3267"],"issn-type":[{"value":"2831-3267","type":"print"},{"value":"2831-3267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"2025-12-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}