MS risk in immigrants in the McDonald era: A population-based study in Ontario, Canada

Abstract

Objective: To determine risk factors for multiple sclerosis (MS) in immigrants and to compare MS risk in immigrants and long-term residents in Ontario, Canada.

Methods: We applied a validated algorithm to linked, population-based immigration and health claims data to identify incident cases of MS in immigrants and long-term residents between 1994 and 2016. We conducted 2 multivariable Cox proportional hazards regression analyses: 1 analysis limited to the immigrant cohort assessing potential risk factors for developing MS, and 1 analysis 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. Risk was greatest in those <15 years old at landing (referent <15 years; 16-30 years: hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.63-0.85; 31-45 years: HR 0.55, 95% CI 0.47-0.64). Immigrants from the Middle East (HR 1.22, 95% CI 1.06-1.40) were at greater MS risk than immigrants from Western nations; all other regions had lower risk (p < 0.0001). 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 < 0.0001), although this lower risk was attenuated with longer residence in Canada.

Conclusions: MS incidence in immigrants to Ontario, Canada, varied widely by region of origin, with greatest risk seen in those from the Middle East. Longer residence in Canada was associated with increased risk, even with migration in adulthood, suggesting that environmental exposures into adulthood contribute to MS risk.

Figure 1. Selection of the overall immigrant and matched immigrant cohorts

We selected immigrants arriving from 1985 on who had at least 2 years of Ontario Health Insurance Plan eligibility and 2 years of follow-up during the study. All eligible immigrants made up the first cohort. The second cohort comprised all immigrants who could be matched against long-term Ontario residents by age, sex, and urban residence. DOLC = date of last contact; MS = multiple sclerosis.

Figure 2. Risk of MS in immigrants to Ontario by country of origin

Risk was estimated with a Cox proportional hazards model adjusted for age, sex, neighborhood income quintile (low vs high), weighted Aggregated Diagnosis Groups score, refugee status, urban residence, and time elapsed since landing. Error bars depict 95% confidence intervals. Countries listed individually had at least 20 multiple sclerosis (MS) cases by December 21, 2014. The United Kingdom was used as the reference group.