Background: Vitamin D, a fat soluble vitamin that is mainly involved in the regulation of calcium/phosphate metabolism, has a increasingly understood role in immunomodulatory activity, both in innate and adaptive immune system. In rheumatoid arthritis (RA), vitamin D showed to suppress the proliferation of synoviocytes and to reduce the production of proinfammatory cytokines, in vitro. (1) Recently the hypothesis has been raised that vitamin D has a negative association with RA activity. (2)
Objectives: This study aimed to evaluate the relationship between the 25-hydroxyvitamin D (25(OH) vitD) level, RA activity and response to a first biologic disease-modifying drug (bDMARD).
Methods: This is a longitudinal, retrospective study including consecutive patients with the diagnosis of RA followed at our rheumatology department. Demographic, clinical, and laboratorial data were collected from our national database at baseline, 6 and 12 months after initiation of a first bDMARD. Statistical analysis was performed using SPSS 23.0. Correlations between variables were studied using Spearman correlation analysis and comparison between groups was performed using Wilcoxon and Kruskal-Wallis tests; p<0.05 was considered statistically significant.
Results: Mean age of patients (n=236) was 51.5 ± 11.2 years old, 192 (81.4%) were females with a median disease duration of 10.1 [4.7, 16.7] years. Seropositivity for anti-citrullinated protein antibodies was present in 192 (81.4%) patients and for rheumatoid factor in 175 (74.2%). The majority exhibited a very high or high disease activity at baseline (median DAS28 5.75 [4.99 – 6.63]) and 90% (n=212) of them were concomitantly using corticosteroids and/or other disease-modifying anti-rheumatic drugs (117 with methotrexate (MTX), 62 with leflunomide and 32 with sulfasalazine). Regarding bDMARD, 56.8% (n=134) initiated an TNF alpha inhibitor.
After 6 and 12 months from a bDMARD initiation there was a significant reduction of ESR, CRP levels, TJCs, SJCs and DAS28 (all p-values < 0.001), as expected. Median baseline serum 25(OH) vitD concentrations was 25.5 [16.5, 30.0] ng/ml; notably, 34.2% of our sample was affected by hypovitaminosis D at baseline (25(OH) vitD< 20 ng/mL).
Among our study population 42.5% patients were responders to first bDMARD (23.8% good and 18.7% moderate responders) according to the EULAR response criteria. Disease remission (DAS28 < 2.6) was achieved by 17.6% of patients.
The percentage of good responders was significantly lower in the subgroup of patients with hypovitaminosis D compared to subjects with normal 25(OH) vitamin D levels at baseline (p=0.002), as it was for the percentage of disease remission (p=0.015).
The bivariate correlation analyses showed that 25(OH) vit D levels at baseline correlated with CRP levels and good response to RA treatment after 12 months (Spearman’s coefficient -0.201, p = 0.028; Spearman’s coefficient 0.255, p < 0.019, respectively). 25(OH) vit D levels at baseline, 6 and 12 months after bDMARD initiation did not correlate with age, BMI, ESV, number of tender or swollen joints, DAS28, HAQ or with SDAI or CDAI at 6 or 12 months of treatment.
Conclusion: In patients with RA, basal 25(OH) vit D levels correlated with response to a bDMARD. These results suggest a role of basal vitamin D status in the prediction of disease evolution and support the hypothesis that vitamin D has an immunomodulatory potential.
References: Huhtakangas JA, Veijola J, Turunen S et al. 1,25(OH)2D3 and calcipotriol, its hypocalcemic analog, exert a long-lasting anti-infammatory and anti-proliferative effect in synoviocytes cultured from patients with rheumatoid arthritis and osteoarthritis. J Steroid Biochem Mol Biol 2017; 173: 13- 22.
Lee YH, Bae SC. Vitamin D level in rheumatoid arthritis and its correlation with the disease activity: a meta-analysis. Clin Exp Rheumatol. 2016 Sep-Oct;34(5):827-833. Epub 2016 Apr 6. PMID: 27049238.
Disclosure of Interests: None declared
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