The risk of secondary progressive multiple sclerosis is geographically determined but modifiable

Sifat Sharmin, Izanne Roos, Steve Simpson-Yap, Charles Malpas, Marina M. Sánchez, Serkan Ozakbas, Dana Horakova, Eva K. Havrdova, Francesco Patti, Raed Alroughani, Guillermo Izquierdo, Sara Eichau, Cavit Boz, Magd Zakaria, Marco Onofrj, Alessandra Lugaresi, Bianca Weinstock-Guttman, Alexandre Prat, Marc Girard, Pierre DuquetteMurat Terzi, Maria Pia Amato, Rana Karabudak, Francois Grand'Maison, Samia J. Khoury, Pierre Grammond, Jeannette Lechner-Scott, Katherine Buzzard, Olga Skibina, Anneke van der Walt, Helmut Butzkueven, Recai Turkoglu, Ayse Altintas, Davide Maimone, Allan Kermode, Nevin Shalaby, Vincent V. Pesch, Ernest Butler, Youssef Sidhom, Riadh Gouider, Saloua Mrabet, Oliver Gerlach, Aysun Soysal, Michael Barnett, Jens Kuhle, Stella Hughes, Maria J. Sa, Suzanne Hodgkinson, Celia Oreja-Guevara, Radek Ampapa, Thor Petersen, Cristina Ramo-Tello, Daniele Spitaleri, Pamela McCombe, Bruce Taylor, Julie Prevost, Matteo Foschi, Mark Slee, Chris McGuigan, Guy Laureys, Liesbeth V. Hijfte, Koen de Gans, Claudio Solaro, Jiwon Oh, Richard Macdonell, Eduardo Aguera-Morales, Bhim Singhal, Orla Gray, Justin Garber, Bart V. Wijmeersch, Mihaela Simu, Tamara Castillo-Triviño, Jose L. Sanchez-Menoyo, Dheeraj Khurana, Abdullah Al-Asmi, Talal Al-Harbi, Norma Deri, Yara Fragoso, Patrice H. Lalive, L. G.F. Sinnige, Cameron Shaw, Neil Shuey, Tunde Csepany, Angel P. Sempere, Fraser Moore, Danny Decoo, Barbara Willekens, Claudio Gobbi, Jennifer Massey, Todd Hardy, John Parratt, Tomas Kalincik

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4633-4644
Number of pages12
JournalBrain : a journal of neurology
Volume146
Issue number11
Early online dateJun 27 2023
DOIs
Publication statusPublished - Nov 1 2023

Keywords

  • disease-modifying therapy
  • geography
  • health expenditure
  • latitude
  • secondary progressive multiple sclerosis
  • Multiple Sclerosis, Relapsing-Remitting/epidemiology
  • Multiple Sclerosis, Chronic Progressive/epidemiology
  • Ultraviolet Rays
  • Humans
  • Neoplasm Recurrence, Local
  • Multiple Sclerosis/epidemiology
  • Disease Progression

ASJC Scopus subject areas

  • Clinical Neurology

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