Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis.
Journal: Multiple sclerosis (Houndmills, Basingstoke, England)
Volume: 29
Issue: 7
Year of Publication: 2023
Affiliated Institutions: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. Isfahan University of Medical Sciences, Isfahan, Iran. Dokuz Eylul University, Izmir, Turkey. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic. Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait. KTU Medical Faculty Farabi Hospital, Trabzon, Turkey. Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Catania, Italy Multiple Sclerosis Center, University of Catania, Catania, Italy. Department of Neuroscience, Imaging and Clinical Sciences, University G. D'Annunzio, Chieti, Italy. Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. Hospital Universitario Virgen Macarena, Sevilla, Spain. CHUM and Universite de Montreal, Montreal, QC, Canada. Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon. Department of Neurology, Neuroscience Research Center, Golestan University of Medical Sciences, Gorgan, Iran. Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey. Department of Neurology, School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey. Department of Neurology, Box Hill Hospital, Melbourne, VIC, Australia Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia Department of Neurology, The Alfred Hospital, Melbourne, VIC, Australia. Department of Neurology, Box Hill Hospital, Melbourne, VIC, Australia Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia MS Centre, Royal Melbourne Hospital, Melbourne, VIC, Australia. CISSS Chaudière-Appalache, Levis, QC, Canada. Hacettepe University, Ankara, Turkey. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia Department of Neurology, The Alfred Hospital, Melbourne, VIC, Australia. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia. Centro Sclerosi Multipla, UOC Neurologia, ARNAS Garibaldi, Catania, Italy. School of Medicine and Public Health, University Newcastle, Newcastle, NSW, Australia Department of Neurology, John Hunter Hospital, Hunter New England Health, Newcastle, NSW, Australia. Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey. Monash Medical Centre, Melbourne, VIC, Australia Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia. CSSS Saint-Jérôme, Saint-Jerome, QC, Canada. Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy. Hospital Germans Trias i Pujol, Badalona, Spain. Academic MS Center Zuyderland, Department of Neurology, Zuyderland Medical Center, Sittard-Geleen, The Netherlands School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands. Ospedali Riuniti di Salerno, Salerno, Italy. Department of Neuroscience, Neurology Unit, S. Maria delle Croci Hospital of Ravenna, AUSL Romagna, Ravenna, Italy. Nemocnice Jihlava, Jihlava, Czech Republic. Cliniques Universitaires Saint-Luc, Brussels, Belgium Université Catholique de Louvain, Ottignies-Louvain-la-Neuve, Belgium. Brain and Mind Centre, Sydney, NSW, Australia. Neurology, Kasr Al Ainy MS Research Unit (KAMSU), Cairo, Egypt. Department of Neurology, National MS Center, Melsbroek, Belgium. Neurology, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RCNB), Departments of Head, Spine and Neuromedicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland. Department of Neurology, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal. 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. Perron Institute for Neurological and Translational Science, University of Western Australia, Nedlands, WA, Australia Institute of Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia Sir Charles Gairdner Hospital, Nedlands, WA, Australia. Department of Neurology, University Hospital Razi - Manouba, Tunis, Tunisia Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia. Department of Neurology, University Hospital Razi - Manouba, Tunis, Tunisia. Immune Tolerance Laboratory, Ingham Institute and Department of Medicine, University of New South Wales (UNSW), Sydney, NSW, Australia. Department of Neurology, University Hospital Ghent, Ghent, Belgium. Austin Health, Melbourne, VIC, Australia. Department of Neurology, Hospital Clinico San Carlos, Madrid, Spain. Centro de Esclerosis Múltiple de Buenos Aires (CEMBA), Buenos Aires, Argentina. The University of Queensland, Brisbane, QLD, Australia Royal Brisbane and Women's Hospital, Herston, QLD, Australia. Hospital de Galdakao-Usansolo, Galdakao, Spain. Bombay Hospital Institute of Medical Sciences, Mumbai, India. Center of Neuroimmunology, Service of Neurology, Hospital Clinic de Barcelona, Barcelona, Spain. Royal Victoria Hospital, Belfast, UK. Westmead Hospital, Sydney, NSW, Australia. Department of Neurology, ASL Genovese, Genova, Italy Department of Rehabilitation, M.L. Novarese Hospital, Moncrivello, Italy. St. Vincent's University Hospital, Dublin, Ireland. Royal Hobart Hospital, Hobart, TAS, Australia. Groene Hart Ziekenhuis, Gouda, The Netherlands. Department of Neurology, University Hospital Center Zagreb, Zagreb, Croatia University of Zagreb, School of Medicine, Zagreb, Croatia. College of Medicine & Health Sciences and Sultan Qaboos University Hospital, Sultan Qaboos University, Seeb, Oman. Department of Neurology, Victor Babes University of Medicine and Pharmacy, Timișoara, Romania. Hospital Universitario Donostia and IIS Biodonostia, San Sebastián, Spain. Neurology Department, King Fahad Specialist Hospital-Dammam, Khobar, Saudi Arabia. Hospital Universitario de CEMIC, Buenos Aires, Argentina. South Eastern HSC Trust, Belfast, UK. Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. University MS Centre, Hasselt-Pelt, Belgium Noorderhart Rehabilitation & MS Center, Pelt and Hasselt University, Hasselt, Belgium. AHEPA University Hospital, Thessaloniki, Greece. Rashid Hospital, Dubai, United Arab Emirates. St. Michael's Hospital, Toronto, ON, Canada. University Hospital Reina Sofia, Cordoba, Spain. Universidade Metropolitana de Santos, Santos, Brazil. Jewish General Hospital, Montreal, QC, Canada. Geelong Hospital, Geelong, VIC, Australia. Booali Sina Hospital, Neurology Department, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. St. Vincent's Hospital, Fitzroy, Melbourne, VIC, Australia. Department of Neurology, Antwerp University Hospital, Edegem, Belgium Translational Neurosciences Research Group, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium. Concord Repatriation General Hospital, Sydney, NSW, Australia. AZ Alma Ziekenhuis, Damme, Belgium. Hospital General Universitario de Alicante, Alicante, Spain. Lyell McEwin Hospital, Elizabeth Vale, SA, Australia. Division of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK Helen Durham Centre for Neuroinflammation, University Hospital of Wales, Cardiff, UK. MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia. MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, VIC, Australia.
Abstract summary
The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear.To determine whether early non-disabling relapses predict disability accumulation in RRMS.We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up.People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated ( = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs ( = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs ( = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically.This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.Authors & Co-authors: Daruwalla Cyrus C Shaygannejad Vahid V Ozakbas Serkan S Havrdova Eva Kubala EK Horakova Dana D Alroughani Raed R Boz Cavit C Patti Francesco F Onofrj Marco M Lugaresi Alessandra A Eichau Sara S Girard Marc M Prat Alexandre A Duquette Pierre P Yamout Bassem B Khoury Samia J SJ Sajedi Seyed Aidin SA Turkoglu Recai R Altintas Ayse A Skibina Olga O Buzzard Katherine K Grammond Pierre P Karabudak Rana R van der Walt Anneke A Butzkueven Helmut H Maimone Davide D Lechner-Scott Jeannette J Soysal Aysun A John Nevin N Prevost Julie J Spitaleri Daniele D Ramo-Tello Cristina C Gerlach Oliver O Iuliano Gerardo G Foschi Matteo M Ampapa Radek R van Pesch Vincent V Barnett Michael M Shalaby Nevin N D'hooghe Marie M Kuhle Jens J Sa Maria Jose MJ Fabis-Pedrini Marzena M Kermode Allan A Mrabet Saloua S Gouider Riadh R Hodgkinson Suzanne S Laureys Guy G Van Hijfte Liesbeth L Macdonell Richard R Oreja-Guevara Celia C Cristiano Edgardo E McCombe Pamela P Sanchez-Menoyo Jose Luis JL Singhal Bhim B Blanco Yolanda Y Hughes Stella S Garber Justin J Solaro Claudio C McGuigan Chris C Taylor Bruce B de Gans Koen K Habek Mario M Al-Asmi Abdullah A Mihaela Simu S Castillo Triviño Tamara T Al-Harbi Talal T Rojas Juan Ignacio JI Gray Orla O Khurana Dheeraj D Van Wijmeersch Bart B Grigoriadis Nikolaos N Inshasi Jihad J Oh Jiwon J Aguera-Morales Eduardo E Fragoso Yara Y Moore Fraser F Shaw Cameron C Baghbanian Seyed Mohammad SM Shuey Neil N Willekens Barbara B Hardy Todd A TA Decoo Danny D Sempere Angel Perez AP Field Deborah D Wynford-Thomas Ray R Cunniffe Nick G NG Roos Izanne I Malpas Charles B CB Coles Alasdair J AJ Kalincik Tomas T Brown J William L JWL
Study Outcome
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Statistics
Citations : European Medicines Agency (EMA). Tysabri, https://www.ema.europa.eu/en/medicines/human/EPAR/tysabri (2018, accessed 16 March 2022).Authors : 92
Identifiers
Doi : 10.1177/13524585231151951SSN : 1477-0970