Background/Purpose: Vitamin D is an immune-modulating hormone. Low Vitamin D levels have been associated with development of autoimmune disease and higher disease activity in early Rheumatoid Arthritis (RA). Furthermore, Vitamin D supplementation may reduce incidence of autoimmune disease. Finally, low Vitamin D levels have been associated with subsequent mortality in non-autoimmune disease populations. Here in the setting of RA we investigated the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels before starting methotrexate (MTX) therapy and subsequent all-cause mortality in national and local Cleveland Veterans Affairs (VA) cohorts.

Methods: This is a retrospective cohort study of patients with an ICD-9/10 diagnosis of RA seen in Rheumatology clinic visits. The data collected was time oriented around initial prescribing of MTX, a MTX medication possession ratio > 75%, and a clinical 25(OH)D level before starting MTX in the national (n=15,109) and local Cleveland (n=197) VA cohorts. Chart adjudication to verify RA diagnosis and Vitamin D supplementation was performed for the Cleveland cohort (n=197). We examined survival in groups of RA patients with adequate serum 25(OH)D ( > 20 ng/mL) and deficient 25(OH)D ( < 20 ng/mL) levels using Cox Proportional-Hazards Model. The model was adjusted for traditional cardiovascular risk factors, including age, sex, race and ethnicity, smoking status, body mass index (BMI), statin use, and the Charlson comorbidity index. We used a signed rank test to evaluate changes among patients with 25(OH)D levels measured before and after supplementation.

Results: Patients with 25(OH)D levels > 20 ng/mL before starting MTX had a 28% reduced risk of mortality when compared to patients with 25(OH)D levels < 20 ng/mL (HR 0.72; CI 0.64, 0.80; p < 0.001) in the national VA cohort. Age, gender, smoking status, Charlson comorbidity index, and BMI were also independently associated with mortality. We observed higher 25(OH)D levels after Vitamin D supplementation compared to before (p=0.008) in the Cleveland chart-reviewed cohort in which supplementation status was obtained.

Conclusion: RA patients with adequate Vitamin D levels ( > 20 ng/mL) have lower subsequent mortality when compared to those with Vitamin D deficiency ( < 20 ng/mL) in a large national RA cohort receiving standard of care MTX. The relationship between Vitamin D level and mortality held after adjusting for Charlson comorbidity score and traditional cardiovascular disease risk factors. The data from Cleveland demonstrate the feasibility of normalizing serum Vitamin D levels with Vitamin D supplementation in this patient population. The extent to which correction of serum Vitamin D levels in patients who were initially found to be Vitamin D deficient impacts upon all-cause mortality in RA is yet to be determined.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/higher-vitamin-d-levels-before-methotrexate-start-are-associated-with-lower-subsequent-mortality-in-rheumatoid-arthritis/