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1. Vitamin D affects the risk of disease activity in multiple sclerosis

Author

Giordano, Antonino, Clarelli, Ferdinando, Pignolet, Béatrice, Mascia, Elisabetta, Sorosina, Melissa, Misra, Kaalindi, Ferrè, Laura, Bucciarelli, Florence, Manouchehrinia, Ali, Moiola, Lucia, Martinelli, Vittorio, Rocca, Maria A, Liblau, Roland, Filippi, Massimo, and Esposito, Federica

Abstract

BackgroundVitamin D (VitD) affects the risk of multiple sclerosis (MS), but the impact on disease activity is controversial. We assessed whether VitD is associated with the No-Evidence of Disease Activity-3 (NEDA-3) status at 2 years from disease-modifying treatment (DMT) start, and whether this association is causal or the result of confounding factors. Furthermore, we explored if a genetic predisposition to higher VitD levels affects the risk of disease activity.Methods230 untreated relapsing-remitting MS patients underwent serum 25-OH-vitamin-D measurement, and the association between seasonally adjusted VitD and disease activity was tested. Modelling a Polygenic Risk Score from a Genome-Wide Association Study on ~400 000 individuals, we studied the impact of genetic predisposition to higher VitD on the NEDA-3 status in 1408 independent MS patients. Two-sample Mendelian randomisation (MR) was used to assess causality.ResultsLower baseline VitD was associated with decreased probability of NEDA-3 at 2 years (p=0.019). Particularly, VitD levels <20 ng/mL conferred an over twofold risk of disease activity (OR 2.36, 95% CI 1.30 to 3.88, p=0.0037). Genetic predisposition to higher VitD levels was associated with delayed age at MS onset (p=0.018) and with a higher probability of NEDA-3 status (p=0.034). MR confirmed causality between VitD and the risk of disease activity (p=0.041).ConclusionsVitD levels before DMT start affect the risk of disease activity in MS. Genetic predisposition to higher VitD levels confers a lower risk of disease activity and is associated with delayed MS onset. Our work prompts future prospective studies regarding VitD supplementation and lifestyle interventions to hamper disease activity in MS.

Published
2025
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2. Healthcare use is elevated two decades before a first demyelinating event and differs by age and sex.

Author

Tremlett H, Zhu F, Everett K, Asaf A, Manouchehrinia A, Li P, McKay KA, Hillert J, Zhao Y, Maxwell C, and Marrie RA

Subjects
Humans, Male, Female, Adult, Sweden epidemiology, Middle Aged, Sex Factors, Young Adult, Age Factors, Registries, Ontario epidemiology, Adolescent, Cohort Studies, Age of Onset, Aged, Hospitalization statistics & numerical data, Multiple Sclerosis epidemiology, Multiple Sclerosis therapy, Patient Acceptance of Health Care statistics & numerical data
Abstract

Objective: Elevated healthcare use before multiple sclerosis (MS) onset suggests earlier opportunity to identify MS. Yet their timing and sociodemographic effects are unclear. We examined rates of healthcare use (and by age/sex) for >two decades pre-MS onset., Methods: We identified people with MS (PwMS) using administrative data from Canada (Ontario) and Sweden (1991-2020) ("administrative" cohort), and the Swedish MS Registry ("clinical" cohort). The first MS/demyelinating diagnostic code (administrative) or symptom onset (clinical) defined MS onset. We compared annual rates of healthcare use (hospital, physician, and emergency-room [ED]) pre-onset between PwMS and up to five matched population controls using negative binomial regression, and by age/sex., Results: The administrative cohort = 35,018/136,007 PwMS/controls (Ontario), and 10,269/51,297 (Sweden). Rates of healthcare use were higher for PwMS than controls up to 28 (of 29) years (Ontario) and up to 15 (of 19) years (Sweden) pre-onset. Annual healthcare use rose steadily as onset approached, particularly escalating 7 years pre-onset in Ontario (e.g., hospital visit rate ratios [RRs] exceeded 1.30), and 6 years in Sweden (physician visit RRs > 1.10). RRs peaked the year pre-onset (ED visits [Ontario] = 3.04; 95% CI: 2.94-3.13, physician visits [Sweden] = 2.51; 95% CI: 2.44-2.59). In the year pre-onset, RRs were disproportionately higher for males (ED RRs [Ontario] = 3.30; 95% CI: 3.13-3.48 vs. females = 2.90; 95% CI: 2.79-3.02), and dropped steadily by age (physician visit RRs [Sweden] = 2.61/2.27/1.97/1.72 for 50/40/30/20-year-olds). The smaller clinical cohort (7604/37,974 PwMS/controls) exhibited similar patterns, albeit more modest, with RRs elevated up to 5 years pre-onset (physician visit RR [year-5] = 1.08; 95% CI: 1.02-1.14; RR [year-1] = 1.39;1.33-1.46)., Interpretation: Higher healthcare use was evident decades before MS onset, escalating 6-7 years pre-onset, peaking the year before, being disproportionately higher for males and older PwMS., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Published
2025
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