{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:21:41Z","timestamp":1788531701635,"version":"build-2803163510"},"reference-count":27,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10-COHO-002"],"award-info":[{"award-number":["ANR-10-COHO-002"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Early initiation of high-efficacy therapies (HETs) has been associated with improved disease control in pediatric-onset multiple sclerosis (POMS). However, some children remain clinically stable on low-\/moderate-efficacy therapies (METs), highlighting the need for decision-support tools.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To develop a Therapeutic Escalation Score (TES) to identify children at low risk of early escalation after initiating MET.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We analyzed treatment-na\u00efve children with POMS who initiated MET between 2010 and 2024 in the French MS registry (Observatoire Fran\u00e7ais de la Scl\u00e9rose en Plaques (OFSEP)). TES was derived using Cox regression modeling based on baseline clinical and magnetic resonance imaging (MRI) variables, with internal validation in OFSEP and external validation in the Italian MS registry Registro Italiano Sclerosi Multipla (RISM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We included 455 children from OFSEP (training\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u2009303; validation\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u2009152) and 573 from RISM. TES incorporated age, year of treatment initiation, Expanded Disability Status Scale score, prior-year relapses, brain lesion location, and T2 spinal cord lesions. A TES threshold of 1.34 stratified patients by 1-year escalation risk. In OFSEP, low-risk patients had a 1-year escalation probability of 3.6% (negative predictive value: 97.0%). In RISM, discrimination was similar (area under the curve (AUC): 72.8%\u201373.8%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>TES is a baseline-only prognostic tool using routine clinical and MRI data to identify children with POMS unlikely to require early escalation after MET initiation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585261446829","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T06:14:43Z","timestamp":1780380883000},"page":"1038-1051","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["A predictive tool for early treatment escalation after initiation of moderate-efficacy therapy in pediatric-onset multiple sclerosis"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8931-4393","authenticated-orcid":false,"given":"Nail","family":"Benallegue","sequence":"first","affiliation":[{"name":"Department of Paediatric Neurology, Universit\u00e9 Angers, CHU Angers, Angers, France; Nantes Universit\u00e9, CHU Nantes, INSERM, CIC 14131413, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Rollot","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Claude Bernard, Lyon, France; Department of Neurology, H\u00f4pital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, scl\u00e9rose en plaques, pathologies de la my\u00e9line et neuro-infammation, Bron, France; Centre de Recherche en Neurosciences de Lyon, Observatoire Fran\u00e7ais de La Scl\u00e9rose en Plaques, INSERM 1028 et CNRS UMR 5292, Lyon, France; EUGENE DEVIC EDMUS Foundation Against Multiple Sclerosis, State-Approved Foundation, Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2308-1731","authenticated-orcid":false,"given":"Pietro","family":"Iaffaldano","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicines and Neurosciences, University of Bari Aldo Moro, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Lucisano","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicines and Neurosciences, University of Bari Aldo Moro, Bari, Italy; Center for Outcomes Research and Clinical Epidemiology (CORESEARCH), Pescara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4381-4613","authenticated-orcid":false,"given":"Marta","family":"Simone","sequence":"additional","affiliation":[{"name":"Department of Precision, Regenerative Medicine and Ionic Area (DiMePRe-J), University of Bari Aldo Moro, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2902-5589","authenticated-orcid":false,"given":"Alessandra","family":"Lugaresi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and NeuroMotor Sciences, IRCCS Istituto delle Scienze Neurologiche di Bologna\u2014UOSI Riabilitazione Sclerosi Multipla, Universita degli Studi di Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5918-9261","authenticated-orcid":false,"given":"Romain","family":"Casey","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Claude Bernard, Lyon, France; Department of Neurology, H\u00f4pital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, scl\u00e9rose en plaques, pathologies de la my\u00e9line et neuro-infammation, Bron, France; Centre de Recherche en Neurosciences de Lyon, Observatoire Fran\u00e7ais de La Scl\u00e9rose en Plaques, INSERM 1028 et CNRS UMR 5292, Lyon, France; EUGENE DEVIC EDMUS Foundation Against Multiple Sclerosis, State-Approved Foundation, Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3878-8820","authenticated-orcid":false,"given":"Eleonora","family":"Cocco","sequence":"additional","affiliation":[{"name":"Centro Regionale per la diagnosi e la cura della Sclerosi Multipla ASL8\u2014PO Binaghi, Medical Science and Public Health Ospedale Binaghi, University of Cagliari, Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7337-7122","authenticated-orcid":false,"given":"Sandra","family":"Vukusic","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Claude Bernard, Lyon, France; Department of Neurology, H\u00f4pital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, scl\u00e9rose en plaques, pathologies de la my\u00e9line et neuro-infammation, Bron, France; Centre de Recherche en Neurosciences de Lyon, Observatoire Fran\u00e7ais de La Scl\u00e9rose en Plaques, INSERM 1028 et CNRS UMR 5292, Lyon, France; EUGENE DEVIC EDMUS Foundation Against Multiple Sclerosis, State-Approved Foundation, Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"De Luca","sequence":"additional","affiliation":[{"name":"Centro Sclerosi Multipla\u2014Clinica Neurologica Policlinico SS. Annunziata, Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Mathey","sequence":"additional","affiliation":[{"name":"Neurology, Universit\u00e9 de Lorraine, CHRU-Nancy, Nancy, France; Universit\u00e9 de Lorraine, Inserm, INSPIIRE, Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6923-0846","authenticated-orcid":false,"given":"Francesco","family":"Patti","sequence":"additional","affiliation":[{"name":"Department of GF Ingrassia, Section of Neurosciences, Universit\u00e0 degli Studi di Catania, Catania, Italy; Centro Sclerosi Multipla\u2014AOL Policlinico Vittorio Emanuele\u2014Universit\u00e0 di Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7699-0328","authenticated-orcid":false,"given":"Elisabeth","family":"Maillart","sequence":"additional","affiliation":[{"name":"Neurology Department, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, APHP, Paris, France; Centre de Ressources et de Comp\u00e9tences SEP, Paris, France; Centre de R\u00e9f\u00e9rence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3325-3760","authenticated-orcid":false,"given":"Maria Pia","family":"Amato","sequence":"additional","affiliation":[{"name":"Dipartimento NEUROFARBA\u2014Sezione Neuroscienze\u2014Universit\u00e0 degli Studi di Firenze\u2014Centro SM SODc Riabilitazione Neurologica\u2014AOU Careggi, Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Michel","sequence":"additional","affiliation":[{"name":"Neurology Department, Clinical Neuroscience Centre, CIC_P1414 INSERM, Rennes University Hospital, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Fantozzi","sequence":"additional","affiliation":[{"name":"Centro Sclerosi Multipla\u2014IRCCS Neuromed, MS Centre, Pozzilli (IS), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3386-6308","authenticated-orcid":false,"given":"Jonathan","family":"Ciron","sequence":"additional","affiliation":[{"name":"Department of Neurology, CRC-SEP, Centre Hospitalier Universitaire de Toulouse, H\u00f4pital Pierre-Paul Riquet, Toulouse, France; Institut Toulousain Des Maladies Infectieuses Et Inflammatoires (Infinity), INSERM UMR 1291, CNRS UMR 5051, Universit\u00e9 Toulouse III, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"De Robertis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Vito Fazzi, Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"De S\u00e8ze","sequence":"additional","affiliation":[{"name":"Department of Neurology Et Centre d\u2019Investigation Clinique, CHU de Strasbourg, INSERM 1434, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Gabriella","family":"Coniglio","sequence":"additional","affiliation":[{"name":"Center for Multiple Sclerosis Contrada Cattedra Ambulante, Presidio Ospedaliero Madonna delle Grazie, Matera, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0020-8739","authenticated-orcid":false,"given":"Aur\u00e9lie","family":"Ruet","sequence":"additional","affiliation":[{"name":"Department of Neurology, CHU de Bordeaux, Bordeaux, France; Universit\u00e9 de Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-0479","authenticated-orcid":false,"given":"Massimo","family":"Filippi","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, Centro Sclerosi Multipla\u2014IRCCS Ospedale San Raffaele, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Labauge","sequence":"additional","affiliation":[{"name":"CRC SEP, Department of Neurology, University Hospital of Montpellier, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8795-1768","authenticated-orcid":false,"given":"Sebastiano Giuseppe","family":"Crisafulli","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Neurologico Carlo Besta, Neuroimmunology and Neuromuscular Diseases Unit, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Zephir","sequence":"additional","affiliation":[{"name":"P\u00f4le Des Neurosciences Et de L\u2019appareil Locomoteur, CRC-SEP, H\u00f4pital Roger Salengro, Universit\u00e9 de Lille, Inserm, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4818-3806","authenticated-orcid":false,"given":"Diana","family":"Ferraro","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Neurology Unit, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Baggiovara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Papeix","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Fondation Adolphe de Rothschild Hospital, Universit\u00e9 Paris\u2014Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3713-2416","authenticated-orcid":false,"given":"Christine","family":"Lebrun-Frenay","sequence":"additional","affiliation":[{"name":"Department of Neurology, CHU Nice, UR2CA-URRIS Cote d\u2019Azur University, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Trojano","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicines and Neurosciences, University of Bari Aldo Moro, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6113-6938","authenticated-orcid":false,"given":"David Axel","family":"Laplaud","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU Nantes, INSERM, CIC 14131413, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France; CRC-SEP, Department of Neurology, H\u00f4pital Nord Laennec, CHU Nantes, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002884"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.2125"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.5566"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(24)00047-6"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458517732843"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26052"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2023.104942"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25737"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1800149"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.4455"},{"key":"e_1_3_3_12_2","article-title":"Interferon beta-1b in treatment-naive paediatric patients with relapsing-remitting multiple sclerosis: Two-year results from the BETAPAEDIC study","volume":"3","author":"Gartner J","year":"2017","unstructured":"Gartner J, Bruck W, Weddige A, et al. Interferon beta-1b in treatment-naive paediatric patients with relapsing-remitting multiple sclerosis: Two-year results from the BETAPAEDIC study. 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