PT  - JOURNAL ARTICLE
AU  - Giordano, Antonino
AU  - Clarelli, Ferdinando
AU  - Pignolet, Béatrice
AU  - Mascia, Elisabetta
AU  - Sorosina, Melissa
AU  - Misra, Kaalindi
AU  - Ferrè, Laura
AU  - Bucciarelli, Florence
AU  - Manouchehrinia, Ali
AU  - Moiola, Lucia
AU  - Martinelli, Vittorio
AU  - Rocca, Maria A
AU  - Liblau, Roland
AU  - Filippi, Massimo
AU  - Esposito, Federica
TI  - Vitamin D affects the risk of disease activity in multiple sclerosis
AID  - 10.1136/jnnp-2024-334062
DP  - 2024 Jul 13
TA  - Journal of Neurology, Neurosurgery & Psychiatry
PG  - jnnp-2024-334062
4099  - http://jnnp.bmj.com/content/early/2024/07/13/jnnp-2024-334062.short
4100  - http://jnnp.bmj.com/content/early/2024/07/13/jnnp-2024-334062.full
AB  - Background Vitamin 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.Methods 230 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.Results Lower 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).Conclusions VitD 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.Data are available on reasonable request. Anonymized data of the analyses presented in this study are available upon reasonable request from the corresponding author.