MS Risk in Immigrants in the McDonald Era: A Population-Based Study in Ontario, Canada

Abstract

Background: Migration studies may provide insights into environmental determinants of multiple sclerosis (MS) and whether a critical window for exposure exists. We aimed to determine risk factors for MS in immigrants and compare MS risk in immigrants versus long-term residents in Ontario, Canada. Methods: We applied a validated algorithm to linked, population-based immigration and health claims data to identify incident MS cases in immigrants and long term-residents between 1994 and 2016. We conducted two multivariable Cox proportional hazards regression analyses including one limited to the immigrant cohort assessing potential risk factors for developing MS; and one comparing MS risk between immigrants and matched long-term residents (1:3 match). Results: We identified 2,304,302 immigrants for the immigrant-only analysis, of whom 1,526 (0.066%) developed MS. Younger age at migration, female sex, greater co-morbidity burden, lower neighbourhood income, and time since landing were associated with increased MS risk. Risk was greatest in those <15 years old at landing (Ref: <15 years; 16-30 years: HR 0.73, 95%CI: 0.63-0.85; 31-45 years: HR 0.55, 95%CI: 0.47-0.64). Region/country of origin was also associated with MS risk. Immigrants from the Middle East (HR 1.22, 95%CI: 1.06-1.40) were at greater risk than immigrants from Western nations; all other regions had lower MS risk (p<.0001). The matched analysis included 2,207,751 immigrants and 6,362,169 long-term residents. Immigrants were less likely to develop MS than long-term residents (p<.0001), although this lower risk was attenuated with longer residence in Canada. Interpretation: MS incidence in immigrants to Ontario, Canada varied widely by region of origin, with greatest risk seen in those from the Middle East. Although MS risk declined with increasing age at arrival, considerable risk was sustained with migration after age 15, suggesting that environmental exposures into adulthood contribute to MS risk. Funding Statement: This study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Declaration of Interests: DR has received research support from the Consortium of Multiple Sclerosis Centers and from the Multiple Sclerosis Society of Canada. She has served as a consultant for Sanofi Aventis, Biogen, Novartis, EMD Serono, and Roche. RAM receives research funding from the Canadian Institutes of Health Research, Multiple Sclerosis Society of Canada, National Multiple Sclerosis Society, Research Manitoba, the Consortium of MS Centers, Crohn’s and Colitis Canada, and the Waugh Family Chair in Multiple Sclerosis. CJM has received research funding from the Canadian Institutes of Health Research, P.S.I. Foundation, MS Society of Canada, Consortium of MS Centers, MS Scientific Research Foundation, Ontario Ministry of Health and Long-Term Care-Health System Research Fund, Canadian Frailty Network, Partners for Canadian Consortium on Neurodegeneration in Aging, Network for Aging Research-University of Waterloo. She is supported by a University Research Chair at the University of Waterloo. KT receives a research scholar award from the Department of Family and Community Medicine at the University of Toronto. Ethics Approval Statement: This study was approved by the research ethics boards at St. Michael’s Hospital in Toronto, Ontario, Canada. Informed consent by participants was not required.