{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T23:38:55Z","timestamp":1777937935580,"version":"3.51.4"},"reference-count":24,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"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":["Mult Scler"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Objectives:<\/jats:title>\n                    <jats:p>\n                      It remains uncertain whether the relative benefit of disease-modifying treatments (DMTs) diminish as patients age because of a natural decline of inflammatory disease activity. To better capture the balance of benefit and harm, the statistical concept of the\n                      <jats:italic toggle=\"yes\">Number Needed to Treat<\/jats:italic>\n                      (NNT) provides a useful and easily interpretable metric.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We examined the relationship between treatment efficacy and age by applying the NNT concept to three pivotal randomized clinical trials of high-efficacy DMTs: AFFIRM, SENTINEL, and DECIDE (3,954 participants together). NNTs were calculated to determine how many individuals within each age group would need to be treated to prevent one additional inflammatory event (by different definitions of significant inflammation).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Inflammatory disease activity decreased with advancing age, resulting in progressively higher NNTs in older participants. For instance, in the SENTINEL trial, the NNT to prevent one additional new\/enlarging T2 lesion annually was one for the youngest patients (\u2a7d30\u2009years) compared with 10 for the oldest (&gt;50\u2009years). Similarly, in AFFIRM, the NNT to prevent one relapse was two in the youngest group (\u2a7d30\u2009years) versus four in the oldest (41\u201350\u2009years).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion:<\/jats:title>\n                    <jats:p>NNTs provide a framework for contextualizing treatment efficacy against potential harms, supporting more individualized therapeutic decision-making.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585261429245","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T07:18:41Z","timestamp":1773991121000},"page":"429-439","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Diminishing returns of disease-modifying treatment in older participants of multiple sclerosis clinical trials"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6705-5864","authenticated-orcid":false,"given":"Eva","family":"Strijbis","sequence":"first","affiliation":[{"name":"Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jop","family":"Mostert","sequence":"additional","affiliation":[{"name":"Department of Neurology, Rijnstate Hospital, Arnhem, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4378-0089","authenticated-orcid":false,"given":"Miguel","family":"D\u2019Haeseleer","sequence":"additional","affiliation":[{"name":"Universitair Ziekenhuis Brussel, Brussels, Belgium; National Multiple Sclerosis Center, Melsbroek, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ester","family":"Moral","sequence":"additional","affiliation":[{"name":"Neurology, Hospital Universitario de Bellvitge, L\u2019Hospitalet de Llobregat, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Brieva Ruiz","sequence":"additional","affiliation":[{"name":"Neuroimmunology Group, Department of Neurology, Hospital Universitari Arnau de Vilanova, Lleida, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7748-6104","authenticated-orcid":false,"given":"Jacynthe","family":"Comtois","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Montreal, Montreal, QC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6347-5957","authenticated-orcid":false,"given":"Joep","family":"Killestein","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7358-6872","authenticated-orcid":false,"given":"Pavle","family":"Repovic","sequence":"additional","affiliation":[{"name":"Swedish Neuroscience Institute Multiple Sclerosis Center, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3579-5205","authenticated-orcid":false,"given":"Tarrant","family":"McPherson","sequence":"additional","affiliation":[{"name":"Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8455-980X","authenticated-orcid":false,"given":"Gary","family":"Cutter","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9972-5092","authenticated-orcid":false,"given":"Marcus","family":"Koch","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, University of Calgary, Calgary, AB, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012603"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.145805"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/13524585241272938"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00577"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c332"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198806303182605"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2012.12.001"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2019-322348"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa044397"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa044396"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1501481"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","unstructured":"Kurtzke JF. Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology 1983; 33(11): 1444\u20131452.","DOI":"10.1212\/WNL.33.11.1444"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458517703193"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.27034"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.317.7168.1309"},{"key":"e_1_3_2_17_2","unstructured":"Posit [Internet]. Posit. https:\/\/www.posit.co\/ (accessed 18 October 2024)."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2009.08.006"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2021.102988"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2023.578066"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458518775550"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00154-0"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa145"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000013014"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007035"}],"container-title":["Multiple Sclerosis Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13524585261429245","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13524585261429245","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13524585261429245","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:20:43Z","timestamp":1777695643000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13524585261429245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,20]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1177\/13524585261429245"],"URL":"https:\/\/doi.org\/10.1177\/13524585261429245","relation":{},"ISSN":["1352-4585","1477-0970"],"issn-type":[{"value":"1352-4585","type":"print"},{"value":"1477-0970","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,20]]}}}