{
  "abstract": "Background Patients aged ≥35 years at multiple sclerosis (MS) onset with an Expanded Disability Status Scale (EDSS) ≥3 in the first year are at highest risk of aggressive MS (EDSS ≥6 within 10 years). Those without these features are at lowest risk. We aimed to assess whether high-efficacy therapy improves outcomes in high-risk patients and whether its benefit varies by MS severity.Methods This longitudinal cohort study analysed MSBase and OFSEP registry data. Patients were categorized into high- or low-risk of aggressive MS. Within each risk strata, relapse and disability accumulation were compared between those receiving high-efficacy therapy (fingolimod, cladribine, monoclonal antibodies) vs. other/no therapy. Marginal structural models, adjusting for demographics, MS course, relapses, disability, and MRI activity, were used to evaluate treatment effects and interaction with aggressive MS risk.Results 4560 patients (893 high risk, 3667 low risk) were studied. Continuous treatment with high-efficacy therapy vs other/no therapy reduced the risk of relapse and disability accumulation in patients at both high-risk and low-risk of aggressive MS.There was no evidence of an interaction between aggressive MS risk and treatment strategy. The risk of relapse was lowest in patients at low-risk of aggressive MS treated with high-efficacy therapy (HR0.58, 95%CI 0.54–0.62). High-efficacy therapy reduced the risk of disability accumulation across both aggressive MS risk strata.Conclusion High-efficacy therapy reduces relapse and disability accumulation in patients at both high- and low-risk of aggressive MS, with no differential treatment benefit. These findings support widespread use of high-efficacy therapy in relapsing MS.",
  "authors": [
    {
      "affiliations": [
        "CORe Unit, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia",
        "Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia"
      ],
      "name": "Izanne Roos"
    },
    {
      "affiliations": [
        "CORe Unit, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia"
      ],
      "name": "Sifat Sharmin"
    },
    {
      "affiliations": [
        "Department of Neurology, John Hunter Hospital, Hunter New England Health, Newcastle, NSW, Australia"
      ],
      "name": "Jeannette Lechner-Scott"
    },
    {
      "affiliations": [
        "Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia",
        "Department of Neurology, Box Hill Hospital, Monash University, Melbourne, VIC, Australia",
        "Department of Neuroscienes, Eastern health Clinical School, Monash University, Melbourne, VIC, Australia"
      ],
      "name": "Katherine Buzzard"
    },
    {
      "affiliations": [
        "Department of Neuroscienes, Eastern health Clinical School, Monash University, Melbourne, VIC, Australia",
        "Department of Neurology, Alfred Hospital, Melbourne, VIC, Australia",
        "Department of Neurology, Box Hill Hospital, Melbourne, VIC, Australia"
      ],
      "name": "Olga Skibina"
    },
    {
      "affiliations": [
        "Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia",
        "Department of Neurology, Alfred Hospital, Melbourne, VIC, Australia"
      ],
      "name": "Anneke van der Walt"
    },
    {
      "affiliations": [
        "Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia",
        "Department of Neurology, Alfred Hospital, Melbourne, VIC, Australia"
      ],
      "name": "Helmut Butzkueven"
    },
    {
      "affiliations": [
        "Brain and Mind Centre, Sydney, NSW, Australia"
      ],
      "name": "Michael Barnett"
    },
    {
      "affiliations": [
        "Department of Neurology, Austin Health, Melbourne, VIC, Australia",
        "Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia"
      ],
      "name": "Richard Macdonell"
    },
    {
      "affiliations": [
        "Department of Neurology, Monash Health, Clayton, VIC, Australia"
      ],
      "name": "Nevin John"
    },
    {
      "affiliations": [
        "Immune tolerance laboratory Ingham Institute and Dept of Medicine, University of NSW, Sydney, NSW, Australia"
      ],
      "name": "Suzanne Hodgkinson"
    },
    {
      "affiliations": [
        "Flinders University, Adelaide, SA, Australia"
      ],
      "name": "Mark Slee"
    },
    {
      "affiliations": [
        "Department of Neurology, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia",
        "University of Queensland, Brisbane, QLD, Australia"
      ],
      "name": "Pamela McCombe"
    },
    {
      "affiliations": [
        "Westmead Hospital, Sydney, NSW, Australia"
      ],
      "name": "Justin Garber"
    },
    {
      "affiliations": [
        "Perron Institute for Neurological and Translational Science, University of Western Australia, Nedlands, WA, Australia",
        "Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, WA, Australia",
        "Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia"
      ],
      "name": "Allan G Kermode"
    },
    {
      "affiliations": [
        "Perron Institute for Neurological and Translational Science, University of Western Australia, Nedlands, WA, Australia",
        "Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, WA, Australia"
      ],
      "name": "Marzena J Fabis-Pedrini"
    },
    {
      "affiliations": [
        "Perron Institute for Neurological and Translational Science, University of Western Australia, Nedlands, WA, Australia",
        "Sir Charles Gairdner Hospital, Nedlands, WA, Australia"
      ],
      "name": "William M Carroll"
    },
    {
      "affiliations": [
        "Royal Hobart Hospital, Hobart, TAS, Australia",
        "Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia"
      ],
      "name": "Bruce Taylor"
    },
    {
      "affiliations": [
        "University of Lyon, Lyon"
      ],
      "name": "Sandra Vukusic"
    },
    {
      "affiliations": [
        "CORe Unit, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia",
        "Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia"
      ],
      "name": "Tomas Kalincik"
    }
  ],
  "title": "3614 Preserving neurological function in people at high and low risk of aggressive multiple sclerosis",
  "uid": "3775679c-ba8d-53e8-9fd8-533a51157b15"
}