{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:55:21Z","timestamp":1787028921456,"version":"build-2736575974"},"reference-count":21,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background\/Objectives: Uric acid (UA), a major circulating antioxidant, has been consistently reported at lower levels in multiple sclerosis (MS) patients, yet long-term UA trajectories stratified by disease-modifying therapy (DMT) efficacy remain unexplored. This study aimed to evaluate the 5-year longitudinal evolution of serum UA levels in relapsing-remitting MS (RRMS), comparing high-efficacy (HE-DMT) and moderate-efficacy (ME-DMT) treatment groups. Methods: This retrospective longitudinal cohort study included adult RRMS patients who initiated or switched DMTs between January 2020 and June 2025. Serum UA was measured at treatment initiation (T0) and annually for up to 5 years (T1\u2013T5). Linear mixed-effects models adjusted for sex, age, and EDSS were used to examine longitudinal UA trajectories. Results: A total of 222 patients were included and followed for up to 5 years across HE-DMT and ME-DMT treatment groups. Groups were comparable at baseline regarding serum UA levels despite significant differences in age, EDSS, and therapy status. Linear mixed-effects modeling demonstrated that serum UA levels changed significantly over time (F(5, 307.04) = 11.03, p &lt; 0.01), with a significant main effect of treatment type (F(1, 378.31) = 5.25, p = 0.02) and a significant time \u00d7 treatment interaction (F(5, 307.05) = 2.42, p = 0.04), indicating that UA trajectories differed between groups across the follow-up period. In the HE-DMT group, UA levels increased progressively from 4.27 mg\/dL at baseline to 5.58 mg\/dL at year 4, whereas the ME-DMT group showed an initial decline at year 1 followed by a more gradual increase from 4.19 mg\/dL to 5.04 mg\/dL at year 4. Sex was a significant independent predictor of UA levels (p &lt; 0.01), whereas age and EDSS were not. Conclusions: HE-DMTs were associated with an earlier and more pronounced increase in serum UA levels over 5 years compared with ME-DMTs, with distinct trajectories depending on treatment efficacy. These findings suggest that longitudinal UA assessment may serve as a complementary exploratory indicator of the metabolic context associated with DMT efficacy.<\/jats:p>","DOI":"10.3390\/medsci14020256","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T08:50:12Z","timestamp":1778835012000},"page":"256","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Serum Uric Acid Trajectories in Multiple Sclerosis: A 5-Year Longitudinal Comparison of High- and Moderate-Efficacy Therapies"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1544-1325","authenticated-orcid":false,"given":"Laura-Elena","family":"Cucu","sequence":"first","affiliation":[{"name":"Doctoral School, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"S\u0103c\u0103rescu","sequence":"additional","affiliation":[{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"},{"name":"Department of Neurology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1356-9581","authenticated-orcid":false,"given":"Andra","family":"Oancea","sequence":"additional","affiliation":[{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"},{"name":"Department of Medical Specialties I, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6952-9741","authenticated-orcid":false,"given":"Bogdan Emilian","family":"Ignat","sequence":"additional","affiliation":[{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"},{"name":"Department of Neurology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Grosu","sequence":"additional","affiliation":[{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"},{"name":"Department of Neurology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura-Cristina","family":"Baciu","sequence":"additional","affiliation":[{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4813-8057","authenticated-orcid":false,"given":"Costin","family":"Chirica","sequence":"additional","affiliation":[{"name":"Doctoral School, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7004-6846","authenticated-orcid":false,"given":"Gabriela","family":"Popescu","sequence":"additional","affiliation":[{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"},{"name":"Department of Medical Specialties I, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0008-9696","authenticated-orcid":false,"given":"Alexandra","family":"Ma\u0219taleru","sequence":"additional","affiliation":[{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"},{"name":"Department of Medical Specialties I, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5836-1322","authenticated-orcid":false,"given":"Maria-Magdalena","family":"Leon","sequence":"additional","affiliation":[{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"},{"name":"Department of Medical Specialties I, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"589","DOI":"10.2174\/187152712801661194","article-title":"Clonal expansion of mitochondrial DNA deletions and the progression of multiple sclerosis","volume":"11","author":"Campbell","year":"2012","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0165-5728(98)00078-2","article-title":"Peroxynitrite formation within the central nervous system in active multiple sclerosis","volume":"88","author":"Cross","year":"1998","journal-title":"J. Neuroimmunol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tanaka, M., and V\u00e9csei, L. (2020). Monitoring the redox status in multiple sclerosis. 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