{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T10:45:43Z","timestamp":1782211543282,"version":"3.54.5"},"reference-count":48,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Neurol Disord"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Pediatric-onset multiple sclerosis (POMS) is the onset of MS before the age of 18 and accounts for 3%\u20135% of all multiple sclerosis (MS) cases. Natalizumab (NTZ) is among the higher-efficacy disease-modifying treatments (HETs) in MS and is increasingly used for POMS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>In this systematic review and meta-analysis, we aimed to discuss the debate on the efficacy and safety of natalizumab use in POMS, providing quantitative results on relapse rate, disability progression, adverse events (AEs), and JC virus seropositivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>The primary endpoint for meta-analysis was the mean difference (MD) in annualized relapse rate (ARR) after natalizumab compared to before treatment. Secondary outcomes were the MD of Expanded Disability Status Scale (EDSS) and the proportion of POMS patients experiencing AEs and JC virus seropositivity after natalizumab treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data sources and methods:<\/jats:title>\n                    <jats:p>We performed a comprehensive search of PubMed, Embase, Web of Science, and Scopus between January 1, 1991 and May 1, 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In this systematic review, 18 non-randomized interventional studies including 922 patients with POMS were included. Natalizumab therapy was associated with a mean reduction in ARR of \u22121.962 relapses per patient-year from baseline (95% confidence interval (CI): \u22122.449 to \u22121.475;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.001). The drug was also associated with a statistically significant improvement in disability, with a mean change in EDSS of \u22120.807 from baseline (95% CI: \u22121.078 to \u22120.536;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.001). After treatment, 18% of patients experienced AEs (95% CI: 0.11\u20130.25), and JC virus seropositivity was observed in 12% (95% CI: 0.07\u20130.17). No case of progressive multifocal leukoencephalopathy was reported among the 922 natalizumab-treated patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Natalizumab may represent a viable therapeutic option for POMS patients exhibiting highly active disease or serves as an effective alternative in those with inadequate response to initial treatment. The safety profile remains acceptable, with most AEs being manageable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration:<\/jats:title>\n                    <jats:p>PROSPERO (CRD42024583911). This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17562864261440657","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T12:40:37Z","timestamp":1776516037000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Natalizumab for pediatric multiple sclerosis: a systematic review and meta-analysis"],"prefix":"10.1177","volume":"19","author":[{"given":"Yasin","family":"Ebne-Ali-Heydari","sequence":"first","affiliation":[{"name":"School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aryana","family":"Ramezani","sequence":"additional","affiliation":[{"name":"School of Medicine, Isfahan University of Medical Sciences, Isfahan 8174, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirmohammad","family":"Jozayi","sequence":"additional","affiliation":[{"name":"School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9468-1561","authenticated-orcid":false,"given":"Mahdi","family":"Norouzi","sequence":"additional","affiliation":[{"name":"School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parto","family":"Zohrabi","sequence":"additional","affiliation":[{"name":"School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8180-8153","authenticated-orcid":false,"given":"Hasan","family":"Kaveyee","sequence":"additional","affiliation":[{"name":"School of Medicine, Isfahan University of Medical Sciences, Isfahan 8174, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102260"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.5603\/PJNNS.a2020.0069"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2013.06.004"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2025.106263"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/children12030259"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-025-04338-7"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-022-00965-7"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1800149"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-019-0129-0"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-024-12610-y"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(24)00047-6"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1177\/17562864251372752"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-023-01383-4"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.2670"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/1756285610381526"},{"key":"e_1_3_4_17_2","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page MJ","year":"2021","unstructured":"Page MJ, et al. 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