The risk of secondary progressive multiple sclerosis is geographically determined but modifiable.
Journal: Brain : a journal of neurology
Volume: 146
Issue: 11
Year of Publication: 2023
Affiliated Institutions:
CORe, Department of Medicine, University of Melbourne, Melbourne , Australia.
Faculty of Medicine, Dokuz Eylul University, Konak/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.
Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Catania , Italy.
Division of Neurology, Department of Medicine, Amiri Hospital, Sharq , Kuwait.
Multiple Sclerosis Unit, Hospital Universitario Virgen Macarena, Sevilla , Spain.
Faculty of Medicine, Karadeniz Technical University, Karadeniz Technical University Farabi Hospital, Trabzon , Turkey.
Faculty of Medicine, Ain Shams University, Cairo , Egypt.
Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio, Chieti , Italy.
Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna , Italy.
Department of Neurology, Jacobs Multiple Sclerosis Center for Treatment and Research, University at Buffalo, Buffalo , USA.
CHUM MS Center, Faculty of Medicine, Universite de Montreal, Montreal HL M, Canada.
Faculty of Medicine, Mayis University, Samsun , Turkey.
Department NEUROFARBA, University of Florence, Florence , Italy.
Department of Neurology, Hacettepe University, Ankara , Turkey.
Neuro Rive-Sud, Hôpital Charles LeMoyne, Quebec JV J, Canada.
Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut , Lebanon.
Médecine spécialisée, CISSS Chaudière-Appalaches, Levis GX A, Canada.
School of Medicine and Public Health, University of Newcastle, Newcastle , Australia.
Department of Neurology, Box Hill Hospital, Melbourne , Australia.
Department of Neurology, The Alfred Hospital, Melbourne , Australia.
Department of Neurology, Haydarpasa Numune Training and Research Hospital, Istanbul , Turkey.
Department of Neurology, School of Medicine, Koc University, Koc University Research Center for Translational Medicine (KUTTAM), Istanbul , Turkey.
Centro Sclerosi Multipla, UOC Neurologia, ARNAS Garibaldi, Catania , Italy.
Perron Institute, University of Western Australia, Nedlands , Australia.
Department of Neurology, Kasr Al Ainy MS Research Unit (KAMSU), Cairo , Egypt.
Service de Neurologie, Cliniques Universitaires Saint-Luc, Brussels BXL, Belgium.
Monash Medical Centre, Melbourne , Australia.
Department of Neurology, Razi Hospital, Manouba , Tunisia.
Academic MS Center Zuyderland, Department of Neurology, Zuyderland Medical Center, Sittard-Geleen , The Netherlands.
Department of Neurology, Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul , Turkey.
Multiple Sclerosis Clinic, Brain and Mind Centre, Sydney , Australia.
Neurologic Clinic and Policlinic, Departments of Medicine and Clinical Research, University Hospital and University of Basel, Basel , Switzerland.
Department of Neurology, Royal Victoria Hospital, Belfast BT BA, UK.
Department of Neurology, Centro Hospitalar Universitario de Sao Joao, Porto -, Portugal.
Immune tolerance laboratory Ingham Institute and Department of Medicine, University of New South Wales, Sydney , Australia.
Department of Neurology, Hospital Clinico San Carlos, Madrid , Spain.
MS centrum, Nemocnice Jihlava, Jihlava , Czech Republic.
Department of Neurology, Aarhus University Hospital, Arhus C , Denmark.
Department of Neurology, Hospital Germans Trias i Pujol, Badalona , Spain.
Centro Sclerosi Multipla, Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino , Italy.
Royal Brisbane and Women's Hospital, University of Queensland, Brisbane , Australia.
Department of Neurology, Royal Hobart Hospital, Hobart , Australia.
Département de neurologie, CSSS Saint-Jérôme, Saint-Jerome JZ T, Canada.
Department of Neuroscience, Neurology Unit, S. Maria delle Croci Hospital of Ravenna, Ravenna , Italy.
College of Medicine and Public Health, Flinders University, Adelaide , Australia.
Department of Neurology, St Vincent's University Hospital, Dublin D TF, Ireland.
Department of Neurology, Universitary Hospital Ghent, Ghent , Belgium.
Department of Neurology, Groene Hart Hospital, Gouda BB, The Netherlands.
Department of Rehabilitation, CRRF 'Mons. Luigi Novarese', Moncrivello (VC) , Italy.
Barlo Multiple Sclerosis Centre, St. Michael's Hospital, Toronto MBW, Canada.
Department of Neurology, Austin Health, Melbourne , Australia.
Department of Neurology, University Hospital Reina Sofia, Cordoba , Spain.
Department of Neurology, Bombay Hospital Institute of Medical Sciences, Mumbai , India.
Department of Neurology, South Eastern HSC Trust, Belfast BT, UK.
Department of Neurology, Westmead Hospital, Sydney , Australia.
Rehabilitation and MS-Centre Overpelt, Hasselt University, Hasselt , Belgium.
Clinic of Neurology II, Emergency Clinical County Hospital 'Pius Brinzeu', Timisoara , Romania.
Department of Neurology, Hospital Universitario Donostia, San Sebastián , Spain.
Department of Neurology, Hospital de Galdakao-Usansolo, Galdakao , Spain.
Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh , India.
Department of Medicine, Sultan Qaboos University Hospital, Al-Khodh , Oman.
Neurology Department, King Fahad Specialist Hospital-Dammam, Khobar , Saudi Arabia.
Hospital Fernandez, Buenos Aires , Argentina.
Department of Neurology, Universidade Metropolitana de Santos, Santos -, Brazil.
Department of Clinical Neurosciences, Division of Neurology, Faculty of Medicine, Geneva University Hospital, Geneva , Switzerland.
Department of Neurology, Medical Center Leeuwarden, Leeuwarden AD, The Netherlands.
Neuroscience Department, Barwon Health, University Hospital Geelong, Geelong , Australia.
Department of Neurology, St Vincents Hospital, Fitzroy, Melbourne , Australia.
Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen , Hungary.
Department of Neurology, Hospital General Universitario de Alicante, Alicante , Spain.
Department of Neurology, McGill University, Montreal HT E, Canada.
Department of Neurology & Neuro-Rehabilitation, AZ Alma Ziekenhuis, Sijsele-Damme , Belgium.
Department of Neurology, Antwerp University Hospital, Edegem , Belgium.
Ospedale Civico Lugano, Lugano , Switzerland.
St Vincent's Hospital Sydney, Sydney , Australia.
Concord Repatriation General Hospital, Sydney , Australia.
Royal North Shore Hospital, Sydney , Australia.
Abstract summary
Geographical variations in the incidence and prevalence of multiple sclerosis have been reported globally. Latitude as a surrogate for exposure to ultraviolet radiation but also other lifestyle and environmental factors are regarded as drivers of this variation. No previous studies evaluated geographical variation in the risk of secondary progressive multiple sclerosis, an advanced form of multiple sclerosis that is characterized by steady accrual of irreversible disability. We evaluated differences in the risk of secondary progressive multiple sclerosis in relation to latitude and country of residence, modified by high-to-moderate efficacy immunotherapy in a geographically diverse cohort of patients with relapsing-remitting multiple sclerosis. The study included relapsing-remitting multiple sclerosis patients from the global MSBase registry with at least one recorded assessment of disability. Secondary progressive multiple sclerosis was identified as per clinician diagnosis. Sensitivity analyses used the operationalized definition of secondary progressive multiple sclerosis and the Swedish decision tree algorithm. A proportional hazards model was used to estimate the cumulative risk of secondary progressive multiple sclerosis by country of residence (latitude), adjusted for sex, age at disease onset, time from onset to relapsing-remitting phase, disability (Multiple Sclerosis Severity Score) and relapse activity at study inclusion, national multiple sclerosis prevalence, government health expenditure, and proportion of time treated with high-to-moderate efficacy disease-modifying therapy. Geographical variation in time from relapsing-remitting phase to secondary progressive phase of multiple sclerosis was modelled through a proportional hazards model with spatially correlated frailties. We included 51 126 patients (72% female) from 27 countries. The median survival time from relapsing-remitting phase to secondary progressive multiple sclerosis among all patients was 39 (95% confidence interval: 37 to 43) years. Higher latitude [median hazard ratio = 1.21, 95% credible interval (1.16, 1.26)], higher national multiple sclerosis prevalence [1.07 (1.03, 1.11)], male sex [1.30 (1.22, 1.39)], older age at onset [1.35 (1.30, 1.39)], higher disability [2.40 (2.34, 2.47)] and frequent relapses [1.18 (1.15, 1.21)] at inclusion were associated with increased hazard of secondary progressive multiple sclerosis. Higher proportion of time on high-to-moderate efficacy therapy substantially reduced the hazard of secondary progressive multiple sclerosis [0.76 (0.73, 0.79)] and reduced the effect of latitude [interaction: 0.95 (0.92, 0.99)]. At the country-level, patients in Oman, Tunisia, Iran and Canada had higher risks of secondary progressive multiple sclerosis relative to the other studied regions. Higher latitude of residence is associated with a higher probability of developing secondary progressive multiple sclerosis. High-to-moderate efficacy immunotherapy can mitigate some of this geographically co-determined risk.
Authors & Co-authors:
Sharmin Sifat S
Roos Izanne I
Simpson-Yap Steve S
Malpas Charles C
Sánchez Marina M MM
Ozakbas Serkan S
Horakova Dana D
Havrdova Eva K EK
Patti Francesco F
Alroughani Raed R
Izquierdo Guillermo G
Eichau Sara S
Boz Cavit C
Zakaria Magd M
Onofrj Marco M
Lugaresi Alessandra A
Weinstock-Guttman Bianca B
Prat Alexandre A
Girard Marc M
Duquette Pierre P
Terzi Murat M
Amato Maria Pia MP
Karabudak Rana R
Grand'Maison Francois F
Khoury Samia J SJ
Grammond Pierre P
Lechner-Scott Jeannette J
Buzzard Katherine K
Skibina Olga O
van der Walt Anneke A
Butzkueven Helmut H
Turkoglu Recai R
Altintas Ayse A
Maimone Davide D
Kermode Allan A
Shalaby Nevin N
Pesch Vincent V VV
Butler Ernest E
Sidhom Youssef Y
Gouider Riadh R
Mrabet Saloua S
Gerlach Oliver O
Soysal Aysun A
Barnett Michael M
Kuhle Jens J
Hughes Stella S
Sa Maria J MJ
Hodgkinson Suzanne S
Oreja-Guevara Celia C
Ampapa Radek R
Petersen Thor T
Ramo-Tello Cristina C
Spitaleri Daniele D
McCombe Pamela P
Taylor Bruce B
Prevost Julie J
Foschi Matteo M
Slee Mark M
McGuigan Chris C
Laureys Guy G
Hijfte Liesbeth V LV
de Gans Koen K
Solaro Claudio C
Oh Jiwon J
Macdonell Richard R
Aguera-Morales Eduardo E
Singhal Bhim B
Gray Orla O
Garber Justin J
Wijmeersch Bart V BV
Simu Mihaela M
Castillo-Triviño Tamara T
Sanchez-Menoyo Jose L JL
Khurana Dheeraj D
Al-Asmi Abdullah A
Al-Harbi Talal T
Deri Norma N
Fragoso Yara Y
Lalive Patrice H PH
Sinnige L G F LGF
Shaw Cameron C
Shuey Neil N
Csepany Tunde T
Sempere Angel P AP
Moore Fraser F
Decoo Danny D
Willekens Barbara B
Gobbi Claudio C
Massey Jennifer J
Hardy Todd T
Parratt John J
Kalincik Tomas T
Study Outcome
Source Link: Visit source