{
  "abstract": "Introduction Late-onset multiple sclerosis (LOMS) now comprises over 10% of MS diagnoses in contemporary cohorts. The effectiveness of disease-modifying therapies (DMTs) in LOMS is unclear. We aimed to establish the comparative effectiveness of moderate–high-efficacy versus low-efficacy DMTs in LOMS.Methods Using data from the MSBase registry, this multicentre cohort study included people with MS with symptom onset after age 50. Covariates were balanced using inverse-probability-treatment-weighting (IPTW). Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP), confirmed disability improvement (CDI), relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA).Results Of 1032 participants, 472 received moderate–high-efficacy DMTs and 560 received low-efficacy DMTs. IPTW-weighted ARR was 0.06 for moderate–high-efficacy and 0.09 for low-efficacy DMTs, corresponding to an ARR ratio of 0.68 (95% CI 0.50 to 0.93, p=0.01). HR for time to first relapse was 0.66 (95% CI 0.47 to 0.91, p=0.01) in favour of moderate–high-efficacy DMTs.Among 856 participants with adequate follow-up, 37% experienced CDP over a median of 4.43 years, with most events (83.6%) attributable to PIRA. The HR for time to CDP was 0.78 (p=0.08) and RAW was 0.69 (p=0.31) in favour of moderate–high-efficacy DMTs, though neither reached statistical significance. There was no difference in CDI or PIRA.Conclusion Moderate–high-efficacy DMTs reduced relapse risk in LOMS. Relapse activity was low. CDP was common and driven by PIRA. Although the CDP and RAW results did not reach statistical significance, the overall findings support the initial use of moderate–high-efficacy DMTs in LOMS.",
  "authors": [
    {
      "affiliations": [
        "University of Tasmania Menzies Institute for Medical Research, Hobart, Tasmania, Australia",
        "Neurology, Royal Hobart Hospital, Hobart, Tasmania, Australia"
      ],
      "name": "Yi Chao Foong"
    },
    {
      "affiliations": [
        "Department of Neuroscience, Monash University, Clayton, Victoria, Australia"
      ],
      "name": "Daniel Merlo"
    },
    {
      "affiliations": [
        "Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia",
        "Melbourne Brain Centre, Parkville, Victoria, Australia"
      ],
      "name": "Melissa Gresle"
    },
    {
      "affiliations": [
        "Department of Neurology, Box Hill Hospital, Box Hill, Victoria, Australia"
      ],
      "name": "Katherine Buzzard"
    },
    {
      "affiliations": [
        "Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic"
      ],
      "name": "Dana Horakova"
    },
    {
      "affiliations": [
        "Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic"
      ],
      "name": "Eva Kubala Havrdova"
    },
    {
      "affiliations": [
        "Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia",
        "Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia"
      ],
      "name": "Tomas Kalincik"
    },
    {
      "affiliations": [
        "Clinical Outcomes Research Unit, The University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia"
      ],
      "name": "Izanne Roos"
    },
    {
      "affiliations": [
        "Departments of Nephrology and Neurology, Liverpool Hospital, Chipping Norton, New South Wales, Australia",
        "Liverpool Hospital, Liverpool, New South Wales, Australia"
      ],
      "name": "Suzanne Hodgkinson"
    },
    {
      "affiliations": [
        "The University of Newcastle, Newcastle, New South Wales, Australia"
      ],
      "name": "Jeannette Lechner-Scott"
    },
    {
      "affiliations": [
        "UOSI Riabilitazione Sclerosi Multipla, IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy",
        "Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy"
      ],
      "name": "Alessandra Lugaresi"
    },
    {
      "affiliations": [
        "Neurology, Jacobs Comprehensive MS Treatment and Research Center, Buffalo, New York, USA"
      ],
      "name": "Bianca Weinstock-Guttman"
    },
    {
      "affiliations": [
        "Dokuz Eylul University, İzmir, Turkey"
      ],
      "name": "Serkan Ozakbas,"
    },
    {
      "affiliations": [
        "Department of Neuroscience, S Maria delle Croci Hospital, Ravenna, Italy"
      ],
      "name": "Andrea Surcinelli"
    },
    {
      "affiliations": [
        "Neurology Unit, Ospedale S.Maria delle Croci, AUSL Romagna, Ravenna, Italy"
      ],
      "name": "Matteo Foschi"
    },
    {
      "affiliations": [
        "Karadeniz Technical University, Trabzon, Turkey"
      ],
      "name": "Cavit Boz"
    },
    {
      "affiliations": [
        "Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon",
        "American University of Beirut, Beirut, Lebanon"
      ],
      "name": "Samia Joseph Khoury"
    },
    {
      "affiliations": [
        "Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon",
        "Neurology Department, American University of Beirut, Beirut, Lebanon"
      ],
      "name": "Bassem Yamout"
    },
    {
      "affiliations": [
        "Universitair Ziekenhuis Gent, Gent, Belgium"
      ],
      "name": "Guy Laureys"
    },
    {
      "affiliations": [
        "Hospital Clinic and Institut d'Investigació Biomèdica August Pi I Sunyer (IDIBAPS), Center for Neuroimmunology, Service of Neurology Barcelona, ES, Barcelona, Spain"
      ],
      "name": "Yolanda Blanco"
    },
    {
      "affiliations": [
        "Neurosciences, The Alfred, Melbourne, Victoria, Australia"
      ],
      "name": "Olga Skibina"
    },
    {
      "affiliations": [
        "Neurology, University Hospital Basel, Basel, Switzerland"
      ],
      "name": "Jens Kuhle"
    },
    {
      "affiliations": [
        "Department of Medicine, Monash University, Clayton, Victoria, Australia",
        "Department of Neurology, Monash Health, Clayton, Victoria, Australia"
      ],
      "name": "Nevin John"
    },
    {
      "affiliations": [
        "Amiri Hospital, Kuwait City, Kuwait"
      ],
      "name": "Raed Alroughani"
    },
    {
      "affiliations": [
        "Centre integre de sante et de services sociaux des Laurentides point de service de Saint-Jerome, Saint-Jerome, Québec, Canada"
      ],
      "name": "Julie Prevost"
    },
    {
      "affiliations": [
        "Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium"
      ],
      "name": "Vincent Van Pesch"
    },
    {
      "affiliations": [
        "Istituto di Tecnologie Avanzate Biomediche (ITAB), Dipartimento di Neuroscienze e Imaging e Scienze Cliniche; Centro Sclerosi Multipla, Clinica Neurologica, Ospedale SS Annunziata, Università degli Studi Gabriele d’Annunzio Chieti Pescara, Chieti, Italy",
        "Division of Psychological Medicine and Clinical Neurosciences, University Hospital of Wales; Helen Durham Centre for Neuroinflammation, Cardiff University School of Medicine, Cardiff, UK"
      ],
      "name": "Valentina Tomassini"
    },
    {
      "affiliations": [
        "Hôpital Notre Dame, CHUM and Universite de Montreal, Montreal, Québec, Canada"
      ],
      "name": "Alexandre Prat"
    },
    {
      "affiliations": [
        "Hopital Notre Dame, Montreal, Québec, Canada"
      ],
      "name": "Marc Girard"
    },
    {
      "affiliations": [
        "Ondokuz Mayis Üniversitesi, Samsun, Turkey"
      ],
      "name": "Murat Terzi"
    },
    {
      "affiliations": [
        "Neurology, Isfahan University of Medical Sciences, Isfahan, The Islamic Republic of Iran"
      ],
      "name": "Vahid Shaygannejad"
    },
    {
      "affiliations": [
        "Nemocnice Jihlava, Jihlava, Czech Republic"
      ],
      "name": "Radek Ampapa"
    },
    {
      "affiliations": [
        "Department of Neurology, Craigavon Area Hospital, Portadown, UK"
      ],
      "name": "Orla Gray"
    },
    {
      "affiliations": [
        "Isfahan Multiple Sclerosis Society, Isfahan, The Islamic Republic of Iran"
      ],
      "name": "Masoud Etemadifar"
    },
    {
      "affiliations": [
        "Neurology Department, Hospital de São João, Porto, Portugal"
      ],
      "name": "Joana Guimarães"
    },
    {
      "affiliations": [
        "UQCCR, The University of Queensland, Brisbane, Queensland, Australia"
      ],
      "name": "Pamela A McCombe"
    },
    {
      "affiliations": [
        "Department of Neurology, Zuyderland Medical Center, Sittard-Geleen, The Netherlands, Sittard-Geleen, Netherlands"
      ],
      "name": "Oliver Gerlach"
    },
    {
      "affiliations": [
        "Department of Head and Neck Neurology, ASL3 Genovese, Genova, Italy"
      ],
      "name": "Claudio Solaro"
    },
    {
      "affiliations": [
        "Department of Neuroscience, Monash University Central Clinical School, Melbourne, Victoria, Australia"
      ],
      "name": "Helmut Butzkueven"
    },
    {
      "affiliations": [
        "Monash University, Melbourne, Victoria, Australia"
      ],
      "name": "Chao Zhu"
    },
    {
      "affiliations": [
        "Monash University Central Clinical School, Melbourne, Victoria, Australia",
        "Alfred Hospital, Melbourne, Victoria, Australia"
      ],
      "name": "Anneke van der Walt"
    },
    {
      "affiliations": [
        "The Alfred, Melbourne, Québec, Australia"
      ],
      "name": "MSBase Study Group"
    }
  ],
  "title": "Moderate–high efficacy disease-modifying therapies reduce relapse risk in late-onset multiple sclerosis",
  "uid": "54b32e7f-37a9-5353-9e64-c649c042822c"
}