Vitamin D Deficiency Common Among Patients with Systemic Lupus Erythematosus

Vitamin D deficiency was common in systemic lupus erythematosus (SLE) and was more likely to be determined by geographical location rather than disease activity. Results suggest that increased interferon (IFN)-regulated proteins accurately reflected disease activity regardless of vitamin D levels. High-dose oral vitamin D supplementation is a safe and effective way to improve vitamin D levels in this patient population, according to a study published in Arthritis Research and Therapy.¹

“Vitamin D and its link with autoimmune inflammatory diseases is an important ongoing area of research,” investigators explained. “The 2 critical unaddressed questions at present are does vitamin D level determine clinical phenotype in established autoimmune diseases like SLE? Are the current oral vitamin D supplementation protocols in individuals with SLE successful and safe in improving plasma 25-hydroxyvitamin D (25[OH]D) levels along with additional clinical benefits?”

The 2-phase study analyzed the association of plasma vitamin D levels with clinical phenotype, serology, and disease variables in a large cohort of patients with SLE living in north or south India. Both areas vary in ethnicity of people and the amount of sunlight. In phase 1, the cross-sectional portion, plasma 25(OH)D was measured and assessed regarding its association with disease activity, demography, serology, CXCL-10, and Galectin-9. In phase 2, the interventional portion, patients with SLE Disease Activity Index-2000 glucocorticoid index (SLEDAI-2KG) < 10 were randomized to receive either 5 weekly doses of 60,000 units, followed by 60,000 units monthly (high dose), or 30,000 units monthly (routine dose) for a total of 6 months.

Of the 702 patients included in phase 1 (mean age 29.46 years, 93% female), the median plasma vitamin D was 22.83 ng/ml and 41.5% of patients had vitamin D deficiency, defined as < 20 ng/ml. More patients in north India had vitamin D deficiency compared with south India (50.33% vs 34.76%, respectively). Further, patients residing in southern India generally had higher vitamin D levels compared with those living in north India (27.06 ± 20.21 ng/dl vs 17.15 ± 16.07 ng/ml, respectively [p < 0.01]).

A negative correlation of vitamin D with SLEDAI-2K, as well as a positive correlation with age, was observed in univariate analyses. Patients with higher age (30.81 years) were more likely to be in the vitamin D sufficient group. Although Galectin-9 had a modest correlation with SLEDAI-2K, it was not associated with vitamin D levels. Results of multiple linear regression showed that age (β = 0.18) and recruitment center (β = 4.369, p < 0.05) were able to predict plasma vitamin D levels (p < 0.05).

In phase 2, 91 patients, randomized to either routine (n =47) or high dose (n = 44) vitamin D, completed 6 months of supplementation. The median change in plasma vitamin D was more pronounced in the high dose group compared with the routine dose cohort (9.5 [14.5] vs 2.6 [14.6] ng/ml; p = 0.04). A total of 28 patients (63.6%) in the high dose cohort were vitamin D sufficient, compared with 22 (46.8%) in the routine dose cohort at month 6.

Fourteen SLE flares and 6 mild adverse events were reported, including vomiting, diarrhea, and headache, which were equal across both groups.

The large sample size with samples collected at the beginning of enrollment, which decreased the effect of background immunosuppressants, strengthened the study. Additionally, collecting samples year-round mitigated the effect of seasonal variation in vitamin D levels. However, premature termination of the study due to the COVID-19 pandemic limited results.

“Larger sample size with a longer duration of follow-up would be required to obtain meaningful data on the effect of vitamin D supplementation on disease activity,” investigators concluded. “With the current study’s data, it would be important to determine the effect of ethnicity, vitamin D receptor polymorphisms, and alternate methods of vitamin D administration in lupus. High-dose oral vitamin D supplementation seems safe and more effective in improving vitamin D levels in SLE, but its role in modifying disease progress will need further studies.”

Reference:

Kavadichanda C, Singh P, Maurya S, et al. 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. Arthritis Res Ther. 2023;25(1):2. Published 2023 Jan 3. doi:10.1186/s13075-022-02976-7