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Journal article
The risk of secondary progressive multiple sclerosis is geographically determined but modifiable
Brain, Vol.146(11), pp.4633-4644
2023
Abstract
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.
Details
- Title
- The risk of secondary progressive multiple sclerosis is geographically determined but modifiable
- Authors/Creators
- Sifat SharminIzanne RoosSteve Simpson-YapCharles MalpasMarina M SánchezSerkan OzakbasDana HorakovaEva K HavrdovaFrancesco PattiRaed AlroughaniGuillermo IzquierdoSara EichauCavit BozMagd ZakariaMarco OnofrjAlessandra LugaresiBianca Weinstock-GuttmanAlexandre PratMarc GirardPierre DuquetteMurat TerziMaria Pia AmatoRana KarabudakFrancois Grand’MaisonSamia J KhouryPierre GrammondJeannette Lechner-ScottKatherine BuzzardOlga SkibinaAnneke van der WaltHelmut ButzkuevenRecai TurkogluAyse AltintasDavide MaimoneAllan KermodeNevin ShalabyVincent V PeschErnest ButlerYoussef SidhomRiadh GouiderSaloua MrabetOliver GerlachAysun SoysalMichael BarnettJens KuhleStella HughesMaria J SaSuzanne HodgkinsonCelia Oreja-GuevaraRadek AmpapaThor PetersenCristina Ramo-TelloDaniele SpitaleriPamela McCombeBruce TaylorJulie PrevostMatteo FoschiMark SleeChris McGuiganGuy LaureysLiesbeth Van HijfteKoen de GansClaudio SolaroJiwon OhRichard MacdonellEduardo Aguera-MoralesBhim SinghalOrla GrayJustin GarberBart V WijmeerschMihaela SimuTamara Castillo-TriviñoJose L Sanchez-MenoyoDheeraj KhuranaAbdullah Al-AsmiTalal Al-HarbiNorma DeriYara FragosoPatrice H LaliveL G F SinnigeCameron ShawNeil ShueyTunde CsepanyAngel P SempereFraser MooreDanny DecooBarbara WillekensClaudio GobbiJennifer MasseyTodd HardyJohn ParrattTomas Kalincik
- Publication Details
- Brain, Vol.146(11), pp.4633-4644
- Publisher
- Oxford University Press on behalf of the Guarantors of Brain.; OXFORD
- Number of pages
- 12
- Identifiers
- 991005637668707891
- Copyright
- © The Author(s) 2023.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.203 Neuromuscular Disorders
- 1.203.147 Multiple Sclerosis
- Web Of Science research areas
- Clinical Neurology
- Neurosciences
- ESI research areas
- Neuroscience & Behavior