{
  "abstract": "Background Ocrelizumab, a monoclonal antibody targeting CD20+ B cells, is a high-efficacy therapy for multiple sclerosis (MS).Methods Patients with relapse-onset MS treated with ocrelizumab, fingolimod, natalizumab or alemtuzumab for ≥6 months were identified from three registries: MSBase, OFSEP and Danish MS Registry. Pairwise comparisons were performed in the overall cohort and 14 predefined clinicodemographic subgroups based on sex, disease activity, MS duration, Expanded Disability Status Scale, prior therapy and reason for prior treatment cessation. Relapses, progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) were compared in pairwise-censored groups.Results Fingolimod was associated with a higher annualised relapse rate (ARR) (0.14 vs 0.06, p<0.001), relapse risk (HR 2.26, 95% CI 1.98 to 2.58), RAW (1.62, 1.08 to 2.43) and lower risk of disability improvement (0.78, 0.63 to 0.96) than ocrelizumab. Superiority of ocrelizumab over fingolimod on relapses was maintained in all subgroups. Natalizumab was associated with marginally higher ARR (0.10 vs 0.07, p<0.001), relapse risk (1.35, 1.16 to 1.57) and RAW (1.77, 1.07 to 2.94) than ocrelizumab. Alemtuzumab was associated with higher ARR (0.18 vs 0.12, p<0.001) and relapse risk (1.48, 1.25 to 1.76) than ocrelizumab, but there was no evidence for a difference in risk of RAW. There was no evidence for a difference on PIRA in any comparisons. Ocrelizumab was superior to natalizumab and alemtuzumab on relapses in patients who were not treatment-naïve, experienced disease activity on the prior therapy or stopped prior therapy due to lack of efficacy.Conclusions Ocrelizumab provides superior control of relapses and RAW, especially among patients with prior on-treatment disease activity. Treatment of PIRA remains an unmet need.",
  "authors": [
    {
      "affiliations": [
        "Clinical Outcomes Research Unit, The University of Melbourne Department of Medicine Royal Melbourne Hospital, Parkville, Victoria, Australia",
        "Neuroimmunology Centre, Department of Neurology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia"
      ],
      "name": "Izanne Roos"
    },
    {
      "affiliations": [
        "Clinical Outcomes Research Unit, The University of Melbourne Department of Medicine Royal Melbourne Hospital, Parkville, Victoria, Australia",
        "Neuroimmunology Centre, Department of Neurology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia"
      ],
      "name": "Sifat Sharmin"
    },
    {
      "affiliations": [
        "Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic"
      ],
      "name": "Dana Horakova"
    },
    {
      "affiliations": [
        "Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic"
      ],
      "name": "Eva Kubala Havrdova"
    },
    {
      "affiliations": [
        "Department of Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic"
      ],
      "name": "Jana Libertinova"
    },
    {
      "affiliations": [
        "Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic",
        "Department of Neurology, KZ a.s., Hospital Teplice, Prague, Czech Republic"
      ],
      "name": "Marta Vachova"
    },
    {
      "affiliations": [
        "Amiri Hospital, Kuwait City, Kuwait"
      ],
      "name": "Raed Alroughani"
    },
    {
      "affiliations": [
        "Department of Neurology, Karadeniz Technical University, Trabzon, Turkey"
      ],
      "name": "Cavit Boz"
    },
    {
      "affiliations": [
        "Department of Neurology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic"
      ],
      "name": "Zuzana Rous"
    },
    {
      "affiliations": [
        "Department of Neurology, Box Hill Hospital, Box Hill, Victoria, Australia",
        "Monash University Central Clinical School, Melbourne, Victoria, Australia"
      ],
      "name": "Katherine Buzzard"
    },
    {
      "affiliations": [
        "Department of Neurology, Box Hill Hospital, Box Hill, Victoria, Australia",
        "Department of Neurology, The Alfred, Melbourne, Victoria, Australia"
      ],
      "name": "Olga Skibina"
    },
    {
      "affiliations": [
        "Department of Neurology, Faculty of Medicine in Pilsen, Charles University and University Hospital Pilsen, Pilsen, Czech Republic",
        "Faculty of Medicine in Hradec Kralovec, Charles University and University Hospital Hradec Kralove, Hradec Kralove, Czech Republic"
      ],
      "name": "Marek Peterka"
    },
    {
      "affiliations": [
        "Department of Neurology, University Hospital Ostrava, Ostrava, Czech Republic"
      ],
      "name": "Pavel Hradilek"
    },
    {
      "affiliations": [
        "Department of Neurology, Pardubice Hospital, Pardubice, Czech Republic"
      ],
      "name": "Miroslav Mares"
    },
    {
      "affiliations": [
        "Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"
      ],
      "name": "Alasdair Coles"
    },
    {
      "affiliations": [
        "Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"
      ],
      "name": "J William L Brown"
    },
    {
      "affiliations": [
        "Hospital Universitario Virgen Macarena, Sevilla, Spain",
        "Institute of Biomedicine of Sevilla (IBIs), CSI, University of Seville, Seville, Spain"
      ],
      "name": "Sara Eichau Madueño"
    },
    {
      "affiliations": [
        "Neurology Unit, Ospedale S.Maria delle Croci, AUSL Romagna, Ravenna, Italy",
        "Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy"
      ],
      "name": "Matteo Foschi"
    },
    {
      "affiliations": [
        "Centre integre de sante et de services sociaux des Laurentides point de service de Saint-Jerome, Saint-Jerome, Quebec, Canada"
      ],
      "name": "Julie Prevost"
    },
    {
      "affiliations": [
        "Medical Faculty, Ondokuz Mayis Üniversitesi, Samsun, Turkey"
      ],
      "name": "Murat Terzi"
    },
    {
      "affiliations": [
        "Hôpital Notre Dame, CHUM and Universite de Montreal, Montreal, Quebec, Canada"
      ],
      "name": "Alexandre Prat"
    },
    {
      "affiliations": [
        "Hôpital Notre Dame, CHUM and Universite de Montreal, Montreal, Quebec, Canada"
      ],
      "name": "Marc Girard"
    },
    {
      "affiliations": [
        "Multiple Sclerosis Unit, Department of Neurology, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain"
      ],
      "name": "Jose E Meca-Lallana"
    },
    {
      "affiliations": [
        "Department of Medicine, Monash University, Clayton, Victoria, Australia",
        "Department of Neurology, Monash Health, Clayton, Victoria, Australia"
      ],
      "name": "Nevin John"
    },
    {
      "affiliations": [
        "Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy"
      ],
      "name": "Yolanda Blanco"
    },
    {
      "affiliations": [
        "Monash University Central Clinical School, Melbourne, Victoria, Australia",
        "Department of Neuroscience, Monash University Central Clinical School, Melbourne, Victoria, Australia"
      ],
      "name": "Anneke van der Walt"
    },
    {
      "affiliations": [
        "Department of Neuroscience, Monash University Central Clinical School, Melbourne, Victoria, Australia"
      ],
      "name": "Helmut Butzkueven"
    },
    {
      "affiliations": [
        "Université catholique de Louvain, Louvain-la-Neuve, Belgium"
      ],
      "name": "Eva Recmanova"
    },
    {
      "affiliations": [
        "UO Neurologia, Osp Garibaldi, Catania, Italy"
      ],
      "name": "Guy Laureys"
    },
    {
      "affiliations": [
        "Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium"
      ],
      "name": "Radek Ampapa"
    },
    {
      "affiliations": [
        "Department of Neurology, The University of Queensland, Brisbane, Queensland, Australia"
      ],
      "name": "Richard Macdonell"
    },
    {
      "affiliations": [
        "Department of Neurology, Razi University Hospital, Tunis, Tunisia"
      ],
      "name": "Zbysek Pavelek"
    },
    {
      "affiliations": [
        "American University of Beirut, Beirut, Lebanon"
      ],
      "name": "Samia Joseph Khoury"
    },
    {
      "affiliations": [
        "Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy"
      ],
      "name": "Emanuele D’Amico"
    },
    {
      "affiliations": [
        "Department of Neurology, Zuyderland Medical Center, Sittard-Geleen, The Netherlands",
        "School for Mental Health and Neuroscience, Department of Neurology, Maastricht University Medical Centre, Maastricht, The Netherlands"
      ],
      "name": "Oliver Gerlach"
    },
    {
      "affiliations": [
        "Université catholique de Louvain, Louvain-la-Neuve, Belgium",
        "Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium"
      ],
      "name": "Vincent Van Pesch"
    },
    {
      "affiliations": [
        "UO Neurologia, Osp Garibaldi, Catania, Italy"
      ],
      "name": "Davide Maimone"
    },
    {
      "affiliations": [
        "Department of Neurology, Waikato Hospital, Hamilton, New Zealand"
      ],
      "name": "Beatriz Romero-Ferrando"
    },
    {
      "affiliations": [
        "Department of Neurology, The University of Queensland, Brisbane, Queensland, Australia"
      ],
      "name": "Pamela A McCombe"
    },
    {
      "affiliations": [
        "Department of Neurology, Razi University Hospital, Tunis, Tunisia",
        "Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia"
      ],
      "name": "Saloua Mrabet"
    },
    {
      "affiliations": [
        "Neurology, Universitair Ziekenhuis Antwerpen, Edegem, Belgium",
        "Laboratory of Experimental Hematology, Universiteit Antwerpen Faculteit geneeskunde en gezondheidswetenschappen, Wilrijk, Belgium"
      ],
      "name": "Barbara Willekens"
    },
    {
      "affiliations": [
        "Neurology, Hospital Universitario Nacional de Colombia, Bogotá, Colombia"
      ],
      "name": "Simón Cárdenas-Robledo"
    },
    {
      "affiliations": [
        "Neurosciences, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain"
      ],
      "name": "Cristina Ramo-Tello"
    },
    {
      "affiliations": [
        "Department of Neurology, Faculty of Medicine, Masaryk University and University Hospital Brno, Brno, Czech Republic"
      ],
      "name": "Pavel Stourac"
    },
    {
      "affiliations": [
        "Department of Neurology, Hospital Ceske Budejovice, Ceske Budejovice, Czech Republic"
      ],
      "name": "Jana Houskova"
    },
    {
      "affiliations": [
        "Neurology, Isfahan University of Medical Sciences, Isfahan, Iran (the Islamic Republic of)"
      ],
      "name": "Vahid Shaygannejad"
    },
    {
      "affiliations": [
        "Immune Tolerance Laboratory, Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia",
        "Liverpool Hospital Department of Neurology and Neurophysiology, Liverpool, New South Wales, Australia"
      ],
      "name": "Suzanne Hodgkinson"
    },
    {
      "affiliations": [
        "Neurology Unit, P O Unico Macerata, ast Macerata, Macerata, Italy"
      ],
      "name": "Elisabetta Cartechini"
    },
    {
      "affiliations": [
        "Perron Institute, University of Western Australia, Perth, Western Australia, Australia",
        "Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia"
      ],
      "name": "Allan G Kermode"
    },
    {
      "affiliations": [
        "Perron Institute, University of Western Australia, Perth, Western Australia, Australia",
        "Neurology, Western Australian Neuroscience Research Institute, Nedlands, Western Australia, Australia"
      ],
      "name": "Marzena Fabis-Pedrini"
    },
    {
      "affiliations": [
        "Perron Institute, University of Western Australia, Perth, Western Australia, Australia",
        "Western Australian Neuroscience Research Institute, Nedlands, Western Australia, Australia"
      ],
      "name": "William M Carroll"
    },
    {
      "affiliations": [
        "Neurology, Flinders Medical Centre, Adelaide, South Australia, Australia"
      ],
      "name": "Mark Slee"
    },
    {
      "affiliations": [
        "Department of Neurology, Galdakao Hospital, Vizcaya, Spain"
      ],
      "name": "José Luis Sánchez-Menoyo"
    },
    {
      "affiliations": [
        "Sultan Qaboos University College of Medicine and Health Sciences, Seeb, Oman"
      ],
      "name": "Abdullah Al-Asmi"
    },
    {
      "affiliations": [
        "Neurology, Université de Lorraine, CHRU-Nancy, Nancy, France"
      ],
      "name": "Guillaume Mathey"
    },
    {
      "affiliations": [
        "Département de neurologie, Hôpital Pitié-Salpêtrière, Paris, France"
      ],
      "name": "Claire Giannesini"
    },
    {
      "affiliations": [
        "Centre Hospitalier Universitaire de Rennes, Rennes, France"
      ],
      "name": "Laure Michel"
    },
    {
      "affiliations": [
        "Department of Neurology, Centre Hospitalier Universitaire de Toulouse, Toulouse, France"
      ],
      "name": "Jonathan Ciron"
    },
    {
      "affiliations": [
        "LINC, University of Strasbourg and CNRS, Strabsourg, France"
      ],
      "name": "Jérôme De Sèze"
    },
    {
      "affiliations": [
        "Service de Neurologie, Inserm-CHU CIC-P0005, CHU de Bordeaux, Bordeaux, France",
        "Médecine, Université de Bordeaux, Bordeaux, France"
      ],
      "name": "Aurelie Ruet"
    },
    {
      "affiliations": [
        "Neurology, GHICL, Lille, France"
      ],
      "name": "Arnaud Kwiatkowski"
    },
    {
      "affiliations": [
        "Neurology, University of Lille, Lille, France",
        "INSERM U1172, Lille, France"
      ],
      "name": "Helene Zephir"
    },
    {
      "affiliations": [
        "Fondation Ophtalmologique Adolphe de Rothschild, Paris, France"
      ],
      "name": "Caroline Papeix"
    },
    {
      "affiliations": [
        "Neurologie, University of Nice Sophia Antipolis Faculty of Medicine, Nice, France",
        "UR2CA-URRIS, Nice, France"
      ],
      "name": "Christine Lebrun-Frenay"
    },
    {
      "affiliations": [
        "Neurologie, CHU de Dijon, Dijon, France"
      ],
      "name": "Thibault Moreau"
    },
    {
      "affiliations": [
        "Department of Neurology, University hospital, Besancon, France"
      ],
      "name": "Eric Berger"
    },
    {
      "affiliations": [
        "Department of Neurology, University of ClermontFerrand, ClermontFerrand, France"
      ],
      "name": "Pierre Clavelou"
    },
    {
      "affiliations": [
        "Neurology, CHU Marseille, Marseille, France"
      ],
      "name": "Jean Pelletier"
    },
    {
      "affiliations": [
        "Neurologie, Université de Grenoble, Grenoble, France"
      ],
      "name": "Olivier Casez"
    },
    {
      "affiliations": [
        "Neurology, CHU de Rouen, Rouen, France"
      ],
      "name": "Bertrand Bourre"
    },
    {
      "affiliations": [
        "Neurology, Hospital Group Henri Mondor, Créteil, France"
      ],
      "name": "Abir Wahab"
    },
    {
      "affiliations": [
        "Neurology, CHU Limoges, Limoges, France"
      ],
      "name": "Laurent Magy"
    },
    {
      "affiliations": [
        "Neurology, University Hospital of Saint-Etienne, Saint-Etienne, France"
      ],
      "name": "Jean-Philippe Camdessanché"
    },
    {
      "affiliations": [
        "Neurology, CHRU Tours CPU, Saint-Cyr-sur-Loire, France"
      ],
      "name": "Ines Doghri"
    },
    {
      "affiliations": [
        "Department of Neurology, Hôpital Foch, Suresnes, France"
      ],
      "name": "Maia Tchikviladze"
    },
    {
      "affiliations": [
        "Copenhagen University Hospital Danish Multiple Sclerosis Research Center, Glostrup, Denmark"
      ],
      "name": "Finn Sellebjerg"
    },
    {
      "affiliations": [
        "Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen, Denmark"
      ],
      "name": "Jeppe Romme Christensen"
    },
    {
      "affiliations": [
        "Department of Brain and Nerve Diseases, Lillebealt Hospital, Kolding, Denmark",
        "Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark"
      ],
      "name": "Henrik Boye Jensen"
    },
    {
      "affiliations": [
        "Department of Neurology, University of Southern Denmark, Odense, Denmark"
      ],
      "name": "Zsolt Illes"
    },
    {
      "affiliations": [
        "Department of Neurology, Glostrup, Copenhagen University Hospital, Kobenhavn, Denmark"
      ],
      "name": "Stephan Bramow"
    },
    {
      "affiliations": [
        "Department of Neurology, Aarhus University Hospital, Aarhus, Denmark"
      ],
      "name": "Peter V Rasmussen"
    },
    {
      "affiliations": [
        "Department of Neurology, Gødstrup Hospital, Herning, Denmark"
      ],
      "name": "Morten Leif Stilund"
    },
    {
      "affiliations": [
        "Department of Neurology, Aalborg University Hospital, Aalborg, Denmark"
      ],
      "name": "Jakob Schäfer"
    },
    {
      "affiliations": [
        "Brain and Nerve Diseases, Hospital of Southern Jutland, Sønderborg, Denmark"
      ],
      "name": "Matthias Kant"
    },
    {
      "affiliations": [
        "Department of Neurology, Herlev Hospital, Herlev, Denmark",
        "University of Copenhagen Department of Clinical Medicine, Copenhagen, Denmark"
      ],
      "name": "Arkadiusz Weglewski"
    },
    {
      "affiliations": [
        "Service de Neurologie A, Hopital Neurologique, Hospices Civils de Lyon, LyonBron, France",
        "Observatoire Français de la Sclérose en Plaques, Centre de Recherche en Neurosciences de Lyon, INSERM U758-ENS Lyon, Lyon, France"
      ],
      "name": "Sandra Vukusic"
    },
    {
      "affiliations": [
        "The Danish Multiple Sclerosis Registry, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark"
      ],
      "name": "Melinda Magyari"
    },
    {
      "affiliations": [
        "Neurology Department, University Hospital Centre Nantes, Nantes, France",
        "Transplantation and Immunology Research Centre, INSERM, INSERM, Nantes, France"
      ],
      "name": "David-Axel Laplaud"
    },
    {
      "affiliations": [
        "Clinical Outcomes Research Unit, The University of Melbourne Department of Medicine Royal Melbourne Hospital, Parkville, Victoria, Australia",
        "Neuroimmunology Centre, Department of Neurology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia"
      ],
      "name": "Tomas Kalincik"
    },
    {
      "affiliations": [],
      "name": "On behalf of the MSBase, OFSEP and Danish MS Registries"
    }
  ],
  "title": "Comparative effectiveness of ocrelizumab in subgroups of patients with multiple sclerosis: a multi-registry observational cohort study",
  "uid": "66f5e758-ed1b-5ee9-989b-33a81fd68fa1"
}