{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:13:49Z","timestamp":1791288829684,"version":"4.3.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The impact of high-efficacy therapies (HET) on progression independent of relapse and MRI activity (PIRMA) remains poorly defined. In this context, using the French MS registry, we aimed to assess the real-life effectiveness of HET compared with moderate-efficacy therapies (MET) on PIRMA in patients with relapsing-onset multiple sclerosis.<\/jats:p>\n                  <jats:p>Data were collected from patients with relapsing-onset multiple sclerosis of the French MS registry, between January 2010 and June 2023, with a mean follow-up of 3.7 years. Patients with relapsing-onset multiple sclerosis were included in the analysis if they were treated first with HET (2666 included) or MET (7833 included) and had expanded disability status scale and MRI follow-up every 2 years. Each outcome was studied using a propensity score framework. The primary outcome was time to first PIRMA. Secondary outcomes were PIRMA incidence, time to first confirmed disability progression, relapse-associated worsening (RAW), MRI-associated worsening (MAW) and identification of risk factors associated with PIRMA.<\/jats:p>\n                  <jats:p>A total of 10 499 patients fulfilled the inclusion criteria. The mean and standard deviation (SD) age at treatment initiation was 36.4 (10.3) years, with a mean (SD) disease duration of 3.1 (5.1) years.<\/jats:p>\n                  <jats:p>The restricted mean (SD) survival time to first PIRMA was slightly, but significantly shorter in the HET group compared with the MET group [8.7 (0.08) versus 8.9 (0.05) years, P = 0.017]. However, when looking at time to first confirmed disability progression, it tend to be longer in the HET group compared with the MET group [7.6 (0.10) versus 7.3 (0.06) years, P = 0.071], and it was probably linked to the shorter time to first RAW and MAW in the MET group [9.2 (0.06) versus 8.7 (0.05) years, P &amp;lt; 0.001 for RAW; and 9.0 (0.05) versus 8.5 (0.07) years, P &amp;lt; 0.001 for MAW]. Baseline risk factors associated with increased PIRMA incidence in the whole population were high expanded disability status scale, higher age at baseline and the presence of spinal cord lesions.<\/jats:p>\n                  <jats:p>Even if HET gives better control on disability accumulation related to disease activity than MET, our real-life study suggests that PIRMA-related mechanisms are not differentially affected by HET versus MET.<\/jats:p>","DOI":"10.1093\/brain\/awag060","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T12:42:19Z","timestamp":1770813739000},"page":"2022-2031","source":"Crossref","is-referenced-by-count":8,"title":["Progression independent of relapse and MRI activity and treatment strategies in multiple sclerosis"],"prefix":"10.1093","volume":"149","author":[{"given":"Fabien","family":"Rollot","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Claude Bernard Lyon 1 , Lyon F-69000 ,","place":["France"]},{"name":"Service de Neurologie, Scl\u00e9rose en Plaques, Pathologies de la My\u00e9line et Neuro-Inflammation, Hospices Civils de Lyon , Bron F-69677 ,","place":["France"]},{"name":"Observatoire Fran\u00e7ais de la Scl\u00e9rose en Plaques, Centre de Recherche en Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292 , Lyon F-69003 ,","place":["France"]},{"name":"EUGENE DEVIC EDMUS Foundation Against Multiple Sclerosis, State-Approved Foundation , Bron F-69677 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Casey","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Claude Bernard Lyon 1 , Lyon F-69000 ,","place":["France"]},{"name":"Service de Neurologie, Scl\u00e9rose en Plaques, Pathologies de la My\u00e9line et Neuro-Inflammation, Hospices Civils de Lyon , Bron F-69677 ,","place":["France"]},{"name":"Observatoire Fran\u00e7ais de la Scl\u00e9rose en Plaques, Centre de Recherche en Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292 , Lyon F-69003 ,","place":["France"]},{"name":"EUGENE DEVIC EDMUS Foundation Against Multiple Sclerosis, State-Approved Foundation , Bron F-69677 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Kerbrat","sequence":"additional","affiliation":[{"name":"Neurology Department, MOBIDIC U_1236, Rennes University Hospital , Rennes F-35000 ,","place":["France"]},{"name":"Clinical Neuroscience Centre, CIC_P1414 INSERM, Rennes, University Hospital, Rennes University , Rennes F-35000 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Edan","sequence":"additional","affiliation":[{"name":"Neurology Department, MOBIDIC U_1236, Rennes University Hospital , Rennes F-35000 ,","place":["France"]},{"name":"Clinical Neuroscience Centre, CIC_P1414 INSERM, Rennes, University Hospital, Rennes University , Rennes F-35000 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Le Page","sequence":"additional","affiliation":[{"name":"Neurology Department, MOBIDIC U_1236, Rennes University Hospital , Rennes F-35000 ,","place":["France"]},{"name":"Clinical Neuroscience Centre, CIC_P1414 INSERM, Rennes, University Hospital, Rennes University , Rennes F-35000 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Vukusic","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Claude Bernard Lyon 1 , Lyon F-69000 ,","place":["France"]},{"name":"Service de Neurologie, Scl\u00e9rose en Plaques, Pathologies de la My\u00e9line et Neuro-Inflammation, Hospices Civils de Lyon , Bron F-69677 ,","place":["France"]},{"name":"Observatoire Fran\u00e7ais de la Scl\u00e9rose en Plaques, Centre de Recherche en Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292 , Lyon F-69003 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F-34295 ,","place":["France"]},{"name":"Department of Neurology, University of Montpellier (MUSE) , Montpellier F-34000 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Papeix","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fondation Rotschild , Paris F-75000 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Zephir","sequence":"additional","affiliation":[{"name":"CHU Lille, CRCSEP Lille, U1172, Univ Lille , Lille F-59000 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3713-2416","authenticated-orcid":false,"given":"Christine","family":"Lebrun-Frenay","sequence":"additional","affiliation":[{"name":"Neurology, UR2CA-URRIS, Centre Hospitalier Universitaire Pasteur2, Universit\u00e9 Nice C\u00f4te D\u2019Azur , Nice F-06000 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