Impact of season on the association between vitamin D levels at diagnosis and one-year remission in early Rheumatoid Arthritis

Abstract

the study evaluates associations between serum vitamin D metabolites at diagnosis and one-year remission, in early diagnosed rheumatoid arthritis(RA). The CIMESTRA-cohort comprised 160 newly diagnosed RA patients, treated aiming at remission. Vitamin D supplementation was recommended according to national guidelines. D total (25OHD 2 + 25OHD 3) was dichotomized at 50 nmol/L, 1,25(OH) 2 D was categorized in tertiles. Primary outcome was remission(DAS28-CRP ≤ 2.6) after one year. Associations were evaluated using logistic regression, further adjusted for pre-specified potential confounders: Age, sex, symptom-duration before diagnosis, DAS28-CRP and season of diagnosis. Results are presented as Odds Ratios(OR) with 95% Confidence Intervals(95%CIs). In univariate analyses, neither D total nor 1,25(OH) 2 D were associated with remission. In adjusted analyses, low D total was associated with higher odds for remission; OR 2.6, 95%CI (1.1; 5.9) p = 0.03, with season impacting results the most. one-year remission was lower in patients with diagnosis established at winter. in conclusion, low D total at diagnosis was associated with increased probability of achieving one-year remission in early RA when adjusting for covariates. Diagnosis in winter was associated with lower odds for one-year remission. Results suggest that season act as a contextual factor potentially confounding associations between vitamin D and RA disease-course. The finding of low D total being associated with higher one-year remission remains speculative. Mounting evidence suggests vitamin D as an important immune-modulator 1,2. Circulating 25OHD 3 is produced in the skin upon sun-exposure, dependent on e.g. season and latitude 3 , and circannual variation in 25OHD is well-known in Northern latitude 4. 25OHD serves as substrate for conversion into the active metabolite; 1,25(OH) 2 D, both in the kidneys 3 and locally in macrophages, dendritic cells and lymphocytes 5. Immunomodulation by sufficient levels of 1,25(OH) 2 D includes altered differentiation and maturation of dendritic cells, macrophages and lymphocytes 5 , and inhibition of pro-inflammatory cytokines 6. The main-effect of vitamin D on the immune system is to balance the immune-response away from the self-aggressive Th1/ Th17-response and towards the tolerogenic Th2/Th-regulatory response 7,8 .

Involvement of the secosteroid vitamin D in autoimmune rheumatic diseases and COVID-19

“…In addition, the season of clinical onset of RA, according to data from 736 patients with RA in a multicentre study, seems to predict the severity of the disease. In fact, RA onset during spring or winter (with low exposure to solar UVB and hence low synthesis of vitamin D) rather than summer or autumn was reportedly associated with faster erosive radiographic progression (already at 6 months), together with a lower probability of disease remission at 1 year 189 , 190 .…”

Seasonal and Treatment-Related Variation in 25-Hydroxy Vitamin D Concentration in Patients with Rheumatoid Arthritis

“…Seasonal variations in 25-OH-D concentration depend on geographic location and is a factor that can lead to seasonal differences in RA activity [13,[36][37][38]. A study on the Swedish population revealed a significant seasonal variation in 25-OH-D concentration associated with the intensity of UV-B irradiation [36].…”

Dosing Strategy of Vitamin D therapy in Patients with Rheumatic Diseases in Bahrain

“…On the other hand, the weekly high dose of cholecalciferol compared to monthly therapy with the same dose was not only safe, effective, and faster in increasing 25(OH)D serum levels, but also associated with a greater improvement of muscular function (Corrado, Rotondo, Cici, Berardi, & Cantatore, 2021). Additionally, low vitamin D is associated with a low rate of one-year remission in patients with early rheumatoid arthritis whose diagnosis was established in winter (Herly et al, 2020). Also, it has been shown that in RA patients a better response to Tocilizumab (anti-IL-6 antibodies) when patients have sufficient serum vitamin D. Tocilizumab and 1,25(OH)2D synergistically suppress IL-17 production and osteoclast differentiation (Kim et al, 2020).…”