November 06, 2025

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Higher Vitamin D Levels Prior To Methotrexate Initiation May Lower Mortality In RA, Study Finds

Higher Vitamin D Levels before Methotrexate initiation tied to Lower Mortality in rheumatoid arthritis suggests a new study published in the Nutrients.
Vitamin D deficiency is associated with mortality in the general population and has been observed in one rheumatoid arthritis (RA) cohort. Vitamin D is a hormone with immune-modulating effects. While Vitamin D is traditionally known for its impact on bone homeostasis, it also regulates immune function in multiple domains including autoimmune diseases such as rheumatoid arthritis (RA). From a patient perspective, there is increasing interest in “natural” or adjunct treatment options for autoimmune diseases including rheumatoid arthritis. Here, they investigate the relationship between 25-hydroxyvitamin D (25(OH)D) levels before methotrexate (MTX) therapy initiation in patients with rheumatoid arthritis and the subsequent all-cause mortality in a national Veterans Affairs (VA) cohort. This is a retrospective study on rheumatoid arthritis patients time-oriented around the initial methotrexate prescription and 25(OH)D levels before starting methotrexate.
They examined survival in patients with 25(OH)D levels > 50 nmol/L and ≤50 nmol/L using the Cox Proportional Hazard Model and fully adjusted for risk factors. (3) In total, 15,109 rheumatoid arthritis patients were included in the nationwide cohort. rheumatoid arthritis patients with 25(OH)D levels > 50 nmol/L before starting methotrexate had a 28% reduced risk of mortality when compared to those with levels ≤ 50 nmol/L (HR: 0.72, CI: 0.64–0.80, p < 0.001) after adjusting for traditional risk factors. In this national rheumatoid arthritis cohort receiving standard-of-care methotrexate, patients with 25(OH)D levels > 50 nmol/L have lower subsequent mortality when compared to those with 25(OH)D levels ≤ 50 nmol/L. It remains to be determined whether increasing Vitamin D levels in rheumatoid arthritis patients initially found to be Vitamin D deficient impacts their all-cause mortality.
Reference:
Malakooti SK, Siddiqui H, Wilson B, et al. Higher Vitamin D Levels Before Methotrexate Therapy Initiation Are Associated with Lower Subsequent Mortality in Patients with Rheumatoid Arthritis. Nutrients. 2024;16(3):401. Published 2024 Jan 30. doi:10.3390/nu16030401

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