{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T23:31:50Z","timestamp":1777937510675,"version":"3.51.4"},"reference-count":36,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"EDMUS Foundation"},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1129189"],"award-info":[{"award-number":["1129189"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1140766"],"award-info":[{"award-number":["1140766"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1157717"],"award-info":[{"award-number":["1157717"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007459","name":"Multiple Sclerosis International Federation","doi-asserted-by":"publisher","award":["MSIF-ARSEP McDonald Fellowship Grant"],"award-info":[{"award-number":["MSIF-ARSEP McDonald Fellowship Grant"]}],"id":[{"id":"10.13039\/501100007459","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1\u2009year of exposure to MS treatment and 3\u2009years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>High baseline disability scores, annualised relapse rate (ARR) \u2a7e 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) &lt; 6 and ARR &lt; 1 had mean lag of 26.6\u2009weeks (95% CI = 18.2\u201334.9), males with EDSS &lt; 6 and ARR &lt; 1 31.0\u2009weeks (95% CI = 25.3\u201336.8), females with EDSS &lt; 6 and ARR \u2a7e 1 44.8\u2009weeks (95% CI = 24.5\u201365.1), and females with EDSS \u2a7e 6 and ARR &lt; 1 54.3\u2009weeks (95% CI = 47.2\u201361.5).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1352458520981300","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T19:41:45Z","timestamp":1610653305000},"page":"1838-1851","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Determinants of therapeutic lag in multiple sclerosis"],"prefix":"10.1177","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0371-3666","authenticated-orcid":false,"given":"Izanne","family":"Roos","sequence":"first","affiliation":[{"name":"CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia\/Melbourne MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia"}]},{"given":"Emmanuelle","family":"Leray","sequence":"additional","affiliation":[{"name":"Rennes University, EHESP, REPERES \u2013 EA 7449, Rennes, France\/Rennes University, CHU Rennes, Inserm, CIC 1414 [(Centre d\u2019Investigation Clinique de Rennes)], Rennes, France"}]},{"given":"Federico","family":"Frascoli","sequence":"additional","affiliation":[{"name":"Faculty of Science, Engineering and Technology, School of Science, Department of Mathematics, Swinburne University of Technology, Melbourne, VIC, Australia"}]},{"given":"Romain","family":"Casey","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Claude Bernard Lyon 1, Lyon, France\/Hospices Civils de Lyon, Service de Neurologie, scl\u00e9rose en plaques, pathologies de la my\u00e9line et neuro-inflammation, Bron, France\/Observatoire Fran\u00e7ais de la Scl\u00e9rose en Plaques, Centre de Recherche en Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292, Lyon, France\/EUGENE DEVIC EDMUS Foundation Against Multiple Sclerosis, State-Approved Foundation, Bron, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7737-5834","authenticated-orcid":false,"given":"J William L","family":"Brown","sequence":"additional","affiliation":[{"name":"CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia\/Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1915-0036","authenticated-orcid":false,"given":"Dana","family":"Horakova","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic"}]},{"given":"Eva Kubala","family":"Havrdova","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic"}]},{"given":"Marc","family":"Debouverie","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nancy University Hospital, Nancy, France\/Universit\u00e9 de Lorraine, APEMAC, Nancy, France"}]},{"given":"Maria","family":"Trojano","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6923-0846","authenticated-orcid":false,"given":"Francesco","family":"Patti","sequence":"additional","affiliation":[{"name":"GF Ingrassia Department, University of Catania, Catania, Italy\/Policlinico G Rodolico, Catania, Italy"}]},{"given":"Guillermo","family":"Izquierdo","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen Macarena, Sevilla, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9159-3128","authenticated-orcid":false,"given":"Sara","family":"Eichau","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen Macarena, Sevilla, Spain"}]},{"given":"Gilles","family":"Edan","sequence":"additional","affiliation":[{"name":"Centre hospitalier universitaire de Rennes, H\u00f4pital Pontchaillou, Service de neurologie, CIC1414 INSERM, Rennes, France"}]},{"given":"Alexandre","family":"Prat","sequence":"additional","affiliation":[{"name":"CHUM MS Center and Universite de Montreal, Montreal, QC, Canada"}]},{"given":"Marc","family":"Girard","sequence":"additional","affiliation":[{"name":"CHUM MS Center and Universite de Montreal, Montreal, QC, Canada"}]},{"given":"Pierre","family":"Duquette","sequence":"additional","affiliation":[{"name":"CHUM MS Center and Universite de Montreal, Montreal, QC, Canada"}]},{"given":"Marco","family":"Onofrj","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Imaging, and Clinical Sciences, University G. d\u2019Annunzio, Chieti, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2902-5589","authenticated-orcid":false,"given":"Alessandra","family":"Lugaresi","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italia\/Dipartimento di Scienze Biomediche e Neuromotorie, Universit\u00e0 di Bologna, Bologna, Italia"}]},{"given":"Pierre","family":"Grammond","sequence":"additional","affiliation":[{"name":"CISSS Chaudi\u00e8re-Appalache, L\u00e9vis, QC, Canada"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3386-6308","authenticated-orcid":false,"given":"Jonathan","family":"Ciron","sequence":"additional","affiliation":[{"name":"H\u00f4pital Pierre-Paul Riquet, Department of Neurology, CHU de Toulouse, CRC-SEP, Toulouse, France"}]},{"given":"Aur\u00e9lie","family":"Ruet","sequence":"additional","affiliation":[{"name":"University Bordeaux, Bordeaux, France\/INSERM U1215, Neurocentre Magendie, Bordeaux, France\/Department of Neurology, CHU de Bordeaux, CIC Bordeaux CIC1401, Bordeaux, France"}]},{"given":"Serkan","family":"Ozakbas","sequence":"additional","affiliation":[{"name":"Dokuz Eylul University, Konak\/Izmir, Turkey"}]},{"given":"J\u00e9r\u00f4me","family":"De Seze","sequence":"additional","affiliation":[{"name":"CHU de Strasbourg, Department of Neurology and Clinical Investigation Center, CIC (centre d\u2019investigation clinique) INSERM 1434, Strasbourg, France"}]},{"given":"C\u00e9line","family":"Louapre","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau, ICM, Assistance Publique H\u00f4pitaux de Paris APHP, D\u00e9partement de neurologie, H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re, Paris, France"}]},{"given":"H\u00e9l\u00e8ne","family":"Zephir","sequence":"additional","affiliation":[{"name":"CHU Lille, CRCSEP Lille, Univ Lille, U1172, Lille, France"}]},{"given":"Maria Jos\u00e9","family":"S\u00e1","sequence":"additional","affiliation":[{"name":"Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o and Universidade Fernando Pessoa, Porto, Portugal"}]},{"given":"Patrizia","family":"Sola","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy"}]},{"given":"Diana","family":"Ferraro","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, Modena, Italy"}]},{"given":"Pierre","family":"Labauge","sequence":"additional","affiliation":[{"name":"CHU de Montpellier, MS Unit, Montpellier, France\/University of Montpellier (MUSE), Montpellier, France"}]},{"given":"Gilles","family":"Defer","sequence":"additional","affiliation":[{"name":"CHU de Caen, MS Expert Centre, Department of Neurology, avenue de la C\u00f4te-de-Nacre, Normandy University, Caen, France"}]},{"given":"Roberto","family":"Bergamaschi","sequence":"additional","affiliation":[{"name":"IRCCS Mondino Foundation, Pavia, Italy"}]},{"given":"Christine","family":"Lebrun-Frenay","sequence":"additional","affiliation":[{"name":"CRCSEP Nice, UR2CA, Universit\u00e9 Nice Cote d\u2019Azur, Centre hospitalier universitaire de Nice, Hopital Pasteur 2, Nice, France"}]},{"given":"Cavit","family":"Boz","sequence":"additional","affiliation":[{"name":"KTU Medical Faculty Farabi Hospital, Trabzon, Turkey"}]},{"given":"Elisabetta","family":"Cartechini","sequence":"additional","affiliation":[{"name":"UOC Neurologia, Azienda Sanitaria Unica Regionale Marche \u2013 AV3, Macerata, Italy"}]},{"given":"Thibault","family":"Moreau","sequence":"additional","affiliation":[{"name":"CHU de Dijon, Department of Neurology, EA4184, Dijon, France"}]},{"given":"David","family":"Laplaud","sequence":"additional","affiliation":[{"name":"CHU de Nantes, Service de Neurologie & CIC015 INSERM, Nantes, France\/CRTI-Inserm U1064, Nantes, France"}]},{"given":"Jeannette","family":"Lechner-Scott","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University Newcastle, Newcastle, NSW, Australia\/Department of Neurology, John Hunter Hospital, Hunter New England Health, Newcastle, NSW, Australia"}]},{"given":"Francois","family":"Grand\u2019Maison","sequence":"additional","affiliation":[{"name":"Neuro Rive-Sud, Quebec, QC, Canada"}]},{"given":"Oliver","family":"Gerlach","sequence":"additional","affiliation":[{"name":"Department of Neurology, Zuyderland Medical Center, Sittard-Geleen, The Netherlands"}]},{"given":"Murat","family":"Terzi","sequence":"additional","affiliation":[{"name":"Medical Faculty, 19 Mayis University, Samsun, Turkey"}]},{"given":"Franco","family":"Granella","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, Parma, Italy\/Department of General Medicine, Parma University Hospital, Parma, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5436-5804","authenticated-orcid":false,"given":"Raed","family":"Alroughani","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait"}]},{"given":"Gerardo","family":"Iuliano","sequence":"additional","affiliation":[{"name":"Ospedali Riuniti di Salerno, Salerno, Italy"}]},{"given":"Vincent","family":"Van Pesch","sequence":"additional","affiliation":[{"name":"Cliniques universitaires Saint-Luc, UCLouvain, Bruxelles, Belgium"}]},{"given":"Bart","family":"Van Wijmeersch","sequence":"additional","affiliation":[{"name":"Rehabilitation and MS-Centre Overpelt and Hasselt University, Hasselt, Belgium"}]},{"given":"Daniele LA","family":"Spitaleri","sequence":"additional","affiliation":[{"name":"Neurological Unit AORN San G. Moscati, Avellino, Italy"}]},{"given":"Aysun","family":"Soysal","sequence":"additional","affiliation":[{"name":"Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey"}]},{"given":"Eric","family":"Berger","sequence":"additional","affiliation":[{"name":"CHU de Besan\u00e7on, Department of Neurology, Besan\u00e7on, France"}]},{"given":"Julie","family":"Prevost","sequence":"additional","affiliation":[{"name":"CSSS Saint-J\u00e9r\u00f4me, Saint-Jerome, QC, Canada"}]},{"given":"Eduardo","family":"Aguera-Morales","sequence":"additional","affiliation":[{"name":"Hospital Universitario Reina Sofia Cordoba (IMIBIC), Cordoba, Spain"}]},{"given":"Pamela","family":"McCombe","sequence":"additional","affiliation":[{"name":"University of Queensland, Brisbane, QLD, Australia\/Royal Brisbane and Women\u2019s Hospital, Herston, QLD, Australia"}]},{"given":"Tamara","family":"Castillo Trivi\u00f1o","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Biodonostia, Hospital Universitario Donostia, San Sebastian, Spain"}]},{"given":"Pierre","family":"Clavelou","sequence":"additional","affiliation":[{"name":"CHU Clermont-Ferrand, Department of Neurology, Clermont-Ferrand, France\/Universit\u00e9 Clermont Auvergne, Inserm, Neuro-Dol, Clermont-Ferrand, France"}]},{"given":"Jean","family":"Pelletier","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, APHM, H\u00f4pital de la Timone, P\u00f4le de Neurosciences Cliniques, Service de Neurologie, Marseille, France"}]},{"given":"Recai","family":"Turkoglu","sequence":"additional","affiliation":[{"name":"Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey"}]},{"given":"Bruno","family":"Stankoff","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9s, UPMC Paris 06, Brain and Spine Institute, ICM, H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re, Inserm UMR S 1127, CNRS UMR 7225, Pars, France\/Department of Neurology, AP-HP, Saint-Antoine Hospital, Paris, France"}]},{"given":"Olivier","family":"Gout","sequence":"additional","affiliation":[{"name":"Fondation Adolphe de Rothschild de l\u2019\u0153il et du cerveau, Department of Neurology, Paris, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8671-7747","authenticated-orcid":false,"given":"Eric","family":"Thouvenot","sequence":"additional","affiliation":[{"name":"CHU de N\u00eemes, Department of Neurology, N\u00eemes, France\/Institut de G\u00e9nomique Fonctionnelle, UMR5203, INSERM 1191, Universit\u00e9 de Montpellier, Montpellier, France"}]},{"given":"Olivier","family":"Heinzlef","sequence":"additional","affiliation":[{"name":"Centre hospitalier intercommunal de Poissy Saint-Germain-en-Laye, Departement of Neurology, Poissy, France"}]},{"given":"Youssef","family":"Sidhom","sequence":"additional","affiliation":[{"name":"Department of Neurology \u2013 LR 18 SP03 \u2013 CIC Neurosciences, Razi Hospital, La Manouba, 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