{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T12:12:49Z","timestamp":1780575169857,"version":"3.54.1"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: The role of age and time-dependent variables in determining the response to disease-modifying therapies (DMTs) has aroused growing interest in the Multiple Sclerosis (MS) field. Although it is a very hot topic, related literature on the subject is considerably lacking. Objectives: The aim of this study is to deepen the understanding of how time-dependent variables influence disability accumulation and drug response in an MS population, assuming DMF as the first-line treatment, and to expand our knowledge of the risk\u2013benefit evaluation of DMF. Methods: We investigated, in a real-world setting, the efficacy of Dimethyl Fumarate (DMF) in naive versus switcher MS patients, correlated with age, in preventing disability accumulation. Starting from an initial population of 234 DMF-treated patients, we selected 169 of them based on their similar time in therapy (TinT) with DMF of 5.9 \u00b1 2.3 year and sex ratio. Of these, 74 were naive and 95 were lateral switchers at the start of treatment. The mean Expanded Disability Status Scale (EDSS), Disease Duration (DD), age and age at onset were compared between groups. Results: The switcher group showed higher EDSS and age compared to the naive group (2.7 vs. 1.8, p &lt; 0.001; 40.2 vs. 35.5, p = 0.005, respectively). Age correlated with DD, EDSS and age at onset in both naive (r = 0.39, p = 0.007; r = 0.53, p = 0.000; r = 0.63, p = 0.000, respectively) and switcher (r = 0.46, p = 0.002; r = 0.49, p = 0.000; r = 0.61, p = 0.000, respectively) groups. Kaplan\u2013Meier curves, adjusted for age, also indicated that the naive group retained an EDSS score status of 0.5\u20133.5 more frequently (p &lt; 0.001) and reached elevated disability less frequently (p = 0.002) than switchers. The mean EDSS percentage ratio between paired naive and switcher patients, representing the differential neurological impairment (DNI), was 69%, inversely correlating with age in both naive (r = \u22120.52, p &lt; 0.001) and switcher patients (r = \u22120.47, p &lt; 0.001). Finally, logistic regression analysis indicated age as an independent and predictive variable with respect to EDSS. Conclusions: We conclude that age is the main contributor to disability progression and the primary predictive factor for treatment effectiveness for DMF in both naive and switcher MS patients.<\/jats:p>","DOI":"10.3390\/ph18111730","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T10:07:03Z","timestamp":1763114823000},"page":"1730","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Age-Related Efficacy of Dimethyl Fumarate in Naive Versus Switcher Multiple Sclerosis Patients: A Multicenter Population-Based Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7587-8112","authenticated-orcid":false,"given":"Roberto","family":"De Masi","sequence":"first","affiliation":[{"name":"Laboratory of Neuroproteomics, Multiple Sclerosis Centre, \u201cF. Ferrari\u201d Hospital, 73042 Casarano, Lecce, Italy"},{"name":"Complex Operative Unit of Neurology, \u201cF. Ferrari\u201d Hospital, 73042 Casarano, Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2403-9228","authenticated-orcid":false,"given":"Stefania","family":"Orlando","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroproteomics, Multiple Sclerosis Centre, \u201cF. Ferrari\u201d Hospital, 73042 Casarano, Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assunta","family":"Greco","sequence":"additional","affiliation":[{"name":"Departmental-Level Simple Operative Unit of Cardiology, \u201cF. Ferrari\u201d Hospital, 73042 Casarano, Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carmela","family":"Costa","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Ophthalmology, \u201cV. Fazzi\u201d Hospital, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1177\/1352458520970841","article-title":"Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition","volume":"26","author":"Walton","year":"2020","journal-title":"Mult. Scler."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0165-5728(99)00081-8","article-title":"Pathogenesis of tissue injury in MS lesions","volume":"98","author":"Trapp","year":"1999","journal-title":"J. Neuroimmunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0074-7742(07)79006-2","article-title":"Molecular mimicry in multiple sclerosis","volume":"79","author":"Libbey","year":"2007","journal-title":"Int. Rev. 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