Journal Article Ahead of print
PubMed: 42161588 DOI: 10.1136/jnnp-2026-338424
Comparative effectiveness of ocrelizumab in subgroups of patients with multiple sclerosis: a multi-registry observational cohort study.
J Neurol Neurosurg Psychiatry
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 … and 39 other 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.
- Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.
- Department of Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
- 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.
- Amiri Hospital, Kuwait City, Kuwait.
- Department of Neurology, Karadeniz Technical University, Trabzon, Turkey.
- Department of Neurology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.
- Department of Neurology, Box Hill Hospital, Box Hill, Victoria, Australia.
- Monash University Central Clinical School, Melbourne, Victoria, Australia.
- Department of Neurology, The Alfred, Melbourne, Victoria, Australia.
- 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.
- Department of Neurology, University Hospital Ostrava, Ostrava, Czech Republic.
- Department of Neurology, Pardubice Hospital, Pardubice, Czech Republic.
- Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
- Hospital Universitario Virgen Macarena, Sevilla, Spain.
- Institute of Biomedicine of Sevilla (IBIs), CSI, University of Seville, Seville, Spain.
- 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.
- Centre integre de sante et de services sociaux des Laurentides point de service de Saint-Jerome, Saint-Jerome, Quebec, Canada.
- Medical Faculty, Ondokuz Mayis Üniversitesi, Samsun, Turkey.
- Hôpital Notre Dame, CHUM and Universite de Montreal, Montreal, Quebec, Canada.
- Multiple Sclerosis Unit, Department of Neurology, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.
- Department of Medicine, Monash University, Clayton, Victoria, Australia.
- Department of Neurology, Monash Health, Clayton, Victoria, Australia.
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
- Department of Neuroscience, Monash University Central Clinical School, Melbourne, Victoria, Australia.
- Université catholique de Louvain, Louvain-la-Neuve, Belgium.
- UO Neurologia, Osp Garibaldi, Catania, Italy.
- Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
- Department of Neurology, The University of Queensland, Brisbane, Queensland, Australia.
- Department of Neurology, Razi University Hospital, Tunis, Tunisia.
- American University of Beirut, Beirut, Lebanon.
- 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.
- Department of Neurology, Waikato Hospital, Hamilton, New Zealand.
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.
- Neurology, Universitair Ziekenhuis Antwerpen, Edegem, Belgium.
- Laboratory of Experimental Hematology, Universiteit Antwerpen Faculteit geneeskunde en gezondheidswetenschappen, Wilrijk, Belgium.
- Neurology, Hospital Universitario Nacional de Colombia, Bogotá, Colombia.
- Neurosciences, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
- Department of Neurology, Faculty of Medicine, Masaryk University and University Hospital Brno, Brno, Czech Republic.
- Department of Neurology, Hospital Ceske Budejovice, Ceske Budejovice, Czech Republic.
- Neurology, Isfahan University of Medical Sciences, Isfahan, Iran (the Islamic Republic of).
- 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.
- Neurology Unit, P O Unico Macerata, ast Macerata, Macerata, Italy.
- Perron Institute, University of Western Australia, Perth, Western Australia, Australia.
- Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
- Neurology, Western Australian Neuroscience Research Institute, Nedlands, Western Australia, Australia.
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.
MeSH
Registries, Sclerosis, Multiple Sclerosis, Natalizumab, Alemtuzumab, Multiple Chronic Conditions, Cohort Studies, Therapeutics, Neurology