{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T09:39:40Z","timestamp":1788514780706,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Multiple sclerosis (MS) is a major cause of disability, particularly among young adults, with fatigue affecting up to 95% of patients. Despite the availability of disease\u2010modifying therapies (DMTs), their impact on MS\u2010related fatigue (MSF) remains uncertain. This study investigates changes in fatigue levels among individuals with relapsing\u2013remitting MS (RRMS) following the initiation of highly effective therapies (HETs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic search of MEDLINE, PubMed, Scopus, and PsycINFO identified studies involving adults with RRMS treated with HETs and assessed using validated fatigue measures at baseline and follow\u2010up. Data on demographics, MS duration, DMT type, and fatigue scores were extracted. Meta\u2010analyses using a random\u2010effects model calculated standardized mean differences (SMD) in fatigue scores post\u2010treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eighteen studies comprising 4138 RRMS patients and 3806 person\u2010years of follow\u2010up were included. The overall SMD was \u22120.34 (95% CI \u22120.47 to \u22120.21), indicating a small but significant reduction in fatigue. Continuous treatments (e.g., natalizumab, ocrelizumab, fingolimod) showed significant improvements, while immune reconstituting therapies (e.g., alemtuzumab) did not. Among fatigue domains, only physical fatigue showed a significant reduction, particularly with natalizumab (SMD\u2009=\u2009\u22121.25; 95% CI \u22122.43 to \u22120.06) and when assessed using the fatigue scale for motor and cognitive functions scale (SMD\u2009=\u2009\u22121.52; 95% CI \u22122.87 to \u22120.17).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MS\u2010related fatigue levels, especially in its physical aspect, decrease after the initiation of HET. This finding reinforced the role of neuroinflammation in driving fatigue and highlighted the need for domain\u2010specific research and treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70385","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T12:49:49Z","timestamp":1761137389000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>MS<\/scp>\n                    Fatigue Post High\u2010Efficacy Treatment"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9895-5216","authenticated-orcid":false,"given":"C.","family":"Sales","sequence":"first","affiliation":[{"name":"ANU College of Law, Governance and Policy Australian National University  Canberra Australia"},{"name":"Department of Neurology The North Canberra Hospital  Canberra Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Neurology The North Canberra Hospital  Canberra Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1701-7111","authenticated-orcid":false,"given":"T.","family":"Wijeratne","sequence":"additional","affiliation":[{"name":"Department of Neurology &amp; Stroke Services, Western Health  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3842-5683","authenticated-orcid":false,"given":"A.","family":"Bruestle","sequence":"additional","affiliation":[{"name":"John Curtin School of Medical Research Australian National University  Canberra Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6481-0748","authenticated-orcid":false,"given":"N.","family":"Cherbuin","sequence":"additional","affiliation":[{"name":"ANU College of Law, Governance and Policy Australian National University  Canberra Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30443-5"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458517694432"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-021-02396-1"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2024.1457788"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7525-6-100"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2022.103954"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458518799580"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.01074"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph182312445"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7525-4-79"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/17562864211039648"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2023.105065"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-014-0220-1"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.0405"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/20552173211007523"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058643"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2017.10.008"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-022-11134-7"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2023.104677"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-010-9491-z"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-018-0483-0"},{"key":"e_1_2_11_23_1","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions (Version 6.3)","author":"Higgins J. 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