{
  "abstract": "Background: Disability accrual in multiple sclerosis (MS) is heterogeneous. We assessed whether a 2-year multimodal evaluation could identify patients who were developing progression independent of relapse activity (PIRA) or relapse-associated worsening (RAW).\n\nMethods: Among the 81 MS patients with a 2-year follow-up and outcomes determined through 5 years, a composite for PIRA was developed using Firth’s penalized logistic regression analysis; discrimination was calculated as the area under the curve (AUC) using repeated stratified nested cross-validation.\n\nResults: In total, 21 patients (25.9%) met the PIRA criteria, 9 (11.1%) met the RAW criteria, and 1 met both criteria. A multivariate Firth regression analysis selected two variables associated with PIRA after adjustment: Modified Fatigue Impact Scale (MFIS) total score (OR 2.04, 95% CI 1.17–3.83; p = 0.011) and cerebrospinal fluid (CSF) chitinase-3-like protein 1 (CHI3L1) (OR 2.00, 95% CI 1.11–5.26; p = 0.018). Notably, the Symbol Digit Modalities Test (ΔSDMT) showed an association in the univariate analysis (OR 0.47, 95% CI 0.23–0.82; p = 0.006) but was attenuated in the multivariate analysis [odds ratio (OR) 0.64; p = 0.141]. Oligoclonal immunoglobulin G band (OCB) positivity was universal in PIRA, but the findings are inconclusive due to sparse OCB-negative observations and incomplete OCB data. Worsening gait [ΔTimed 25-Foot Walk (ΔT25FW)] and new T2 lesions showed associations in the univariate analysis that were not retained in the multivariate analysis. None of the variables had a p -value of less than 0.10 for RAW. The median out-of-sample AUC was 0.74 (95% CI 0.68–0.78).\n\nConclusion: A two-year multimodal assessment identified a biologically coherent PIRA composite driven by intrathecal neuroinflammation and fatigue. No reliable RAW predictor was found, and external validation is warranted.",
  "abstract_shown": true,
  "affiliations": [
    "Research Group in Immunotherapy and Biomodels for Autoimmunity, Instituto de Investigación Sanitaria La Fe",
    "Department of Neurology, Hospital Dr. Peset",
    "Department of Neurology, Hospital Universitario Vega Baja",
    "Clinical Memory Research Unit, Department of Clinical Sciences, Lund University",
    "Division of Hematology and Oncology, Department of Medicine, Columbia Initiative in Cell Engineering and Therapy (CICET), Columbia University Irving Medical Center"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Luis Rafael Solís-Tarazona"
    },
    {
      "affs": [
        0
      ],
      "name": "Salma Reddam"
    },
    {
      "affs": [
        1
      ],
      "name": "Ana Merchán-Cabanillas"
    },
    {
      "affs": [
        2
      ],
      "name": "Silvia Navarro-Quevedo"
    },
    {
      "affs": [
        3
      ],
      "name": "Lars Lau Raket"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Sara Gil-Perotin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a7wnywwjfyj9z.bib",
  "cited_by": 0,
  "doi": "10.3389/fneur.2026.1902455",
  "fulltext_url": "https://europepmc.org/articles/PMC13710352",
  "id": "a7wnywwjfyj9z",
  "issns": [
    "1664-2295"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fneur.2026.1902455/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2734|Multiple Sclerosis Research Studies"
    ]
  ],
  "openalex": "W7221728057",
  "pdf_url": "https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2026.1902455/pdf",
  "pmcid": "PMC13710352",
  "pmid": "42948123",
  "published": "2026-10-13",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/a7wnywwjfyj9z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:16Z",
      "native_id": "10.3389/fneur.2026.1902455",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fneur.2026.1902455/full"
    },
    {
      "first_seen": "2026-10-31T00:20:34Z",
      "native_id": "MED:42948123",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42948123"
    },
    {
      "first_seen": "2026-10-31T12:21:20Z",
      "native_id": "PMC13710352",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fneur.2026.1902455"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1664-2295",
      "subfield": "neurology"
    }
  ],
  "title": "A 2-year multimodal prospective cohort study to predict sustained progression independent of relapse activity in multiple sclerosis",
  "title_text": "A 2-year multimodal prospective cohort study to predict sustained progression independent of relapse activity in multiple sclerosis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:20Z",
  "url": "https://research.draconitic.com/paper/a7wnywwjfyj9z",
  "venue": "Frontiers in Neurology",
  "versions": []
}