{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:25:58Z","timestamp":1790821558655,"version":"4.1.0"},"reference-count":26,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"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":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Progression independent of relapse and MRI activity (PIRMA) is a major contributor to long-term disability in relapsing-remitting multiple sclerosis (RRMS). In Latin America, limited access to high-efficacy disease-modifying therapies (DMTs) may influence PIRMA risk, but real-world evidence is scarce. We aimed to estimate the causal effect of DMT efficacy on PIRMA in an Argentine cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We conducted a retrospective observational study including 264 adults with RRMS meeting predefined disability follow-up criteria. Treatment exposure was modeled as a time-varying variable (low-efficacy vs moderate-\/high-efficacy), applying a 60-day pharmacological lag after treatment switches. To address time-dependent confounding, we used a marginal structural model with overlap weighting and a weighted Cox proportional hazards model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Median age at treatment initiation was 31.5\u2009years, 62.1% were female, and median baseline EDSS was 1.0. Over a median follow-up of 7\u2009years, 26 PIRMA events occurred. Exposure to low- or moderate-efficacy DMTs was associated with a significantly higher risk of PIRMA compared with high-efficacy therapies (HR 7.05; 95% CI 1.15\u201343.35).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Exposure to low-\/moderate-efficacy disease-modifying therapies was associated with a substantially higher risk of PIRMA compared with high-efficacy treatments, supporting the potential benefit of early access to high-efficacy therapies in RRMS<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585261442036","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:47:01Z","timestamp":1777524421000},"page":"737-746","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Early use of high-efficacy disease-modifying therapies reduces the risk of progression independent of relapse and MRI activity in patients with relapsing-remitting multiple sclerosis"],"prefix":"10.1177","volume":"32","author":[{"given":"Mar\u00eda F","family":"Guarnaschelli","sequence":"first","affiliation":[{"name":"Department of Neurology, Fleni, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4142-8375","authenticated-orcid":false,"given":"Mariano","family":"Marrodan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fleni, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Braian E","family":"Sosa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fleni, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina I","family":"Perez Arana","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fleni, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio F","family":"Farez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fleni, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela P","family":"Fiol","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fleni, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda C","family":"Ysrraelit","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fleni, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4756-9889","authenticated-orcid":false,"given":"Jorge","family":"Correale","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fleni, Buenos Aires, Argentina; IQUIFIB, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"issue":"5","key":"e_1_3_3_2_2","first-page":"1603","article-title":"How patients with multiple sclerosis acquire disability","volume":"145","author":"Lublin FD","year":"2022","unstructured":"Lublin FD, H\u00e4ring DA, Ganjgahi H, et al. How patients with multiple sclerosis acquire disability. Brain 2022; 145(5): 1603\u20131615.","journal-title":"Brain"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac111"},{"issue":"12","key":"e_1_3_3_4_2","article-title":"Using the progression independent of relapse activity framework to unveil the pathobiological foundations of multiple sclerosis","volume":"102","author":"Ciccarelli O","year":"2024","unstructured":"Ciccarelli O, Barkhof F, Calabrese M, et al. Using the progression independent of relapse activity framework to unveil the pathobiological foundations of multiple sclerosis. Neurology 2024; 102(12): e2090\u2013e2102.","journal-title":"Neurology"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.27034"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2023.07.002"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-021-10836-8"},{"key":"e_1_3_3_8_2","first-page":"974","article-title":"Active and non-active progression independent of relapse activity in early relapsing-remitting multiple sclerosis: Association with inflammatory activity","volume":"95","author":"Maarouf A","year":"2024","unstructured":"Maarouf A, Stellmann JP, Rico A, et al. Active and non-active progression independent of relapse activity in early relapsing-remitting multiple sclerosis: Association with inflammatory activity. J Neurol Neurosurg Psychiatry 2024; 95: 974\u2013978.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03901-6"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/0962280216668554"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-200009000-00011"},{"issue":"1","key":"e_1_3_3_12_2","first-page":"250","article-title":"Addressing extreme propensity scores via the overlap weights","volume":"188","author":"Li F","year":"2019","unstructured":"Li F, Thomas LE, Li F. Addressing extreme propensity scores via the overlap weights. Am J Epidemiol 2019; 188(1): 250\u2013257.","journal-title":"Am J Epidemiol"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.3331"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.1568"},{"issue":"10","key":"e_1_3_3_15_2","first-page":"606","article-title":"Multiple sclerosis progression: Time for a new mechanism-driven framework","volume":"19","author":"Kuhlmann T","year":"2023","unstructured":"Kuhlmann T, Moccia M, Coetzee T, et al. Multiple sclerosis progression: Time for a new mechanism-driven framework. 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