Comparative effectiveness of ocrelizumab in subgroups of patients with multiple sclerosis: a multi-registry observational cohort study
Year: 2026
Type: article
Study design: Observational Study
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: Izanne Roos, Sifat Sharmin, Dana Horakova, Eva Kubala Havrdova, Jana Libertinova, Marta Vachova, Raed Alroughani, Cavit Boz, Zuzana Rous, Katherine Buzzard, Olga Skibina, Marek Peterka, Pavel Hradilek, Miroslav Mares, Alasdair Coles, J William L Brown, Sara Eichau Madueño, Matteo Foschi, Julie Prevost, Murat Terzi, Alexandre Prat, Marc Girard, Jose E Meca-Lallana, Nevin John, Yolanda Blanco, Anneke van der Walt, Helmut Butzkueven, Eva Recmanova, Guy Laureys, Radek Ampapa, Richard Macdonell, Zbysek Pavelek, Samia Joseph Khoury, Emanuele D’Amico, Oliver Gerlach, Vincent Van Pesch, Davide Maimone, Beatriz Romero-Ferrando, Pamela A McCombe, Saloua Mrabet, Barbara Willekens, Simón Cárdenas-Robledo, Cristina Ramo-Tello, Pavel Stourac, Jana Houskova, Vahid Shaygannejad, Suzanne Hodgkinson, Elisabetta Cartechini, Allan G Kermode, Marzena Fabis-Pedrini, William M Carroll, Mark Slee, José Luis Sánchez-Menoyo, Abdullah Al-Asmi, Guillaume Mathey, Claire Giannesini, Laure Michel, Jonathan Ciron, Jérôme De Sèze, Aurelie Ruet, Arnaud Kwiatkowski, Helene Zephir, Caroline Papeix, Christine Lebrun-Frenay, Thibault Moreau, Eric Berger, Pierre Clavelou, Jean Pelletier, Olivier Casez, Bertrand Bourre, Abir Wahab, Laurent Magy, Jean-Philippe Camdessanché, Ines Doghri, Maia Tchikviladze, Finn Sellebjerg, Jeppe Romme Christensen, Henrik Boye Jensen, Zsolt Illes, Stephan Bramow, Peter V Rasmussen, Morten Leif Stilund, Jakob Schäfer, Matthias Kant, Arkadiusz Weglewski, Sandra Vukusic, Melinda Magyari, David-Axel Laplaud, Tomas Kalincik
Institutions: The Royal Melbourne Hospital, The University of Melbourne, Charles University, General University Hospital in Prague, University Hospital in Motol, Amiri Hospital, Karadeniz Technical University, University Hospital Olomouc, Palacký University Olomouc, Box Hill Hospital, Monash University, The Alfred Hospital, University Hospital Hradec Králové, University Hospital Ostrava, Pardubice Region, University of Cambridge, Hospital Universitario Virgen Macarena, Instituto de Biomedicina de Sevilla, Universidad de Sevilla, University of L'Aquila, Ospedale "Santa Maria delle Croci" di Ravenna, Centre Intégré de Santé et de Services Sociaux des Laurentides, Ondokuz Mayıs University, Hôpital Notre-Dame, Université de Montréal, Hospital Universitario Virgen de la Arrixaca, Monash Medical Centre, Monash Health, University of Foggia, UCLouvain, Ospedale Garibaldi, Cliniques Universitaires Saint-Luc, The University of Queensland, American University of Beirut, Maastricht University Medical Centre, Zuyderland Medisch Centrum, Waikato Hospital, Waikato District Health Board, Tunis University, Faculté de médecine de Tunis, Tunis El Manar University, University of Antwerp, Antwerp University Hospital, Hospital Universitario Nacional de Colombia, Hospital Universitari Germans Trias i Pujol, Masaryk University, University Hospital Brno, Nemocnice České Budějovice, Isfahan University of Medical Sciences, Liverpool Hospital, Ingham Institute, Ospedale di Macerata, University of Macerata, Murdoch University, The University of Western Australia, Perron Institute for Neurological and Translational Science, Flinders Medical Centre, Hospital de Galdakao, Sultan Qaboos University, Centre Hospitalier Régional et Universitaire de Nancy, Université de Lorraine, Pitié-Salpêtrière Hospital, Centre Hospitalier Universitaire de Rennes, Centre Hospitalier Universitaire de Toulouse, Centre National de la Recherche Scientifique, Université de Strasbourg, Université de Bordeaux, Inserm, Centre Hospitalier Universitaire de Bordeaux, Centre d'Investigation Clinique Plurithématique de Bordeaux, Groupe Hospitalier de l'Institut Catholique de Lille, Université de Lille, Lille Neurosciences & Cognition, Fondation Ophtalmologique Adolphe de Rothschild, Université Nice Sophia Antipolis, CHU Dijon Bourgogne, Centre Hospitalier Universitaire de Besançon, Université Clermont Auvergne, Assistance Publique Hôpitaux de Marseille, Centre Hospitalier Universitaire de Rouen, Centre Hospitalier Universitaire Henri-Mondor, Hôpitaux Universitaires Henri-Mondor, Centre Hospitalier Universitaire de Limoges, Centre Hospitalier Universitaire de Saint-Étienne, Centre Hospitalier Universitaire de Tours, Hôpital Foch, Copenhagen University Hospital, Danish Multiple Sclerosis Center, University of Southern Denmark, Kolding Hospital, Lillebaelt Hospital, Aarhus University Hospital, Regionshospitalet Herning, Aalborg University Hospital, Sygehus Sønderjylland, University of Copenhagen, Herlev Hospital, École Normale Supérieure de Lyon, Centre de Recherche en Neurosciences de Lyon, Hospices Civils de Lyon, Observatoire Français de la Sclérose en Plaques, Rigshospitalet, Centre Hospitalier Universitaire de Nantes, Center for Research in Transplantation and Translational Immunology
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7161815631