Clinical and serological association of plasma 25-hydroxyvitamin D (25(OH)D) levels in lupus and the short-term effects of oral vitamin D supplementation

Background and objectives Data on the association of vitamin D levels and clinical phenotype and disease activity in systemic lupus erythematosus (SLE) is controversial. Further, the optimal dose of oral vitamin D supplementation in SLE is not clear. Thus, the present study was designed to determine the association of plasma vitamin D levels with clinical phenotype, disease variables and serology in a large, cohort of SLE from South Asia and to evaluate the short-term effect of two different dosage regimens of oral vitamin D supplementation on disease flares and plasma vitamin D levels. Methods This is a two-phase study. Phase I was a cross-sectional analytical study of patients from north (26.85° N) and south India (11.94° N). Plasma 25-hydroxyvitamin-D(25(OH)D) was measured, and its association with demography, serology, disease activity, Galectin-9 and CXCL-10 was analysed. In phase II, patients with SLEDAI-2KG < 10 and on stable immunosuppression were randomised to receive either high dose (weekly 60,000 U*5, followed by 60,000 U monthly) or routine dose (30,000 U monthly) oral vitamin D. Outcomes were assessed at 6 months Results Phase I included 702 patients with a mean age of 29.46 + 10.7 years. The median plasma vitamin D was 22.83 (13.8–31.8) ng/ml. Deficiency (< 20 ng/ml) was seen in 41.5% of patients. Patients from South India had higher vitamin D levels (27.06 ± 20.21 ng/dl) as compared to North India (17.15 ± 16.07 ng/ml) ( p < 0.01). Univariate analyses demonstrated weak negative correlation of vitamin D with SLEDAI2K and positive correlation with age. Galactin-9 had modest correlation with SLEDAI2K but not with vitamin D levels. On multiple linear regression, centre of recruitment ( β = 4.37) and age ( β = 0.18) predicted ( p < 0.05) plasma vitamin D levels. In the phase II, 91 randomised to 2 groups completed 6 months. Median change in plasma vitamin D levels was more in high dose (9.5 versus 2.6 ng/ml; p = 0.04). There were 14 SLE flares and six minor adverse events which were equal across both groups. Conclusion Vitamin D deficiency is common in SLE. Geographical location of residence is the major determinant rather than the disease activity. The IFN regulated proteins reflect disease activity independent of vitamin D levels. High-dose oral vitamin D supplementation seems safe and more effective in improving vitamin D levels in SLE. Trial registration The second phase of this study was a registered randomised controlled trial CTRI/2019/06/019658 [registered on: 14/06/2019].