Association Between Serum 25-Hydroxyvitamin D Levels and Inflammatory Markers and Disease Activity in Biologic-Treated Ankylosing Spondylitis Patients

Öz

Aim This study aims to evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and inflammatory markers as well as disease activity in patients with ankylosing spondylitis (AS) receiving biologic therapy, including TNF inhibitors, IL-17 inhibitors, and JAK inhibitors. Material and Methods This cross-sectional study includes 104AS patients receiving biologic therapy for at least six months. Patients were categorized based on serum 25(OH)D levels: deficiency (<20 μg/L), insufficiency(20–30 μg/L), and sufficiency (>30 μg/L). Disease activity was assessed using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) scores. Laboratory parameters, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured. Group comparisons are performed using the Kruskal–Wallis test or one-way ANOVA, as appropriate, and the Chi-square test for categorical variables. Correlations between serum 25(OH)D levels and clinical or laboratory parameters are evaluated using Spearman’s rank correlation analysis. Subgroup analyses are conducted according to biologic treatment class. Results Patients with vitamin D deficiency had significantly higher CRP levels (24.0 mg/L vs. 12.1 mg/L vs. 8.9 mg/L, p=0.001), elevated ESR (p=0.028), and higher BASDAI scores (8.0 vs. 6.7 vs. 5.3, p<0.001) compared to those with insufficiency and sufficiency. Serum 25(OH)D levels were inversely correlated with CRP (r=-0.304, p=0.002) and BASDAI (r=-0.335, p=0.001) in the overall cohort. Subgroup analyses revealed significant negative correlations between 25(OH)D and CRP (r=-0.426, p<0.001) and BASDAI (r=-0.317,p=0.008) in TNF inhibitor-treated patients, and between 25(OH)D and BASDAI (r=-0.609, p=0.001) in IL-17 inhibitor-treated patients. Conclusion Lower serum 25(OH)D levels are significantly associated with higher inflammatory markers and increased disease activity in biologic-treated AS patients. These findings suggest that vitamin D deficiency may be associated with increased inflammatory burden and disease activity in biologic-treated AS patients. Future prospective and interventional studies are needed to determine whether vitamin D supplementation improves clinical outcomes in this population.

Anahtar Kelimeler

• Ankylosing Spondylitis
• 25-hydroxyvitamin D
• Biological therapy
• Disease activity
• Bath Ankylosing Spondylitis Disease Activity Index
• C-reactive protein
• Inflammatory markers

Kaynakça

1. 1. Ward MM, Deodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA, et al. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/ Spondyloarthritis Research and Treatment Network Recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Care Res (Hoboken). 2019;71(10):1285–1299. https://doi.org/10.1002/acr.24025
2. 2. Ranganathan V, Gracey E, Brown MA, Inman RD, Haroon N. Pathogenesis of ankylosing spondylitis -recent advances and future directions. Nat Rev Rheumatol. 2017;13:359–367. https://doi.org/10.1038/nrrheum.2017.56
3. 3. Machado P, Landewe R, Lie E, Kvien TK, Braun J, Baker D, et al. Ankylosing spondylitis disease activity score (ASDAS): defining cut-off values for disease activity states and improvement scores. Ann Rheum Dis. 2011;70:47–53. https://doi.org/10.1136/ard.2010.138594
4. 4. van der Heijde D, Ramiro S, Landewe R, Baraliakos X, Van den Bosch F, Sepriano A, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017;76:978–991. https://doi.org/10.1136/annrheumdis-2016-210770
5. 5. Molto A, Nikiphorou E. Comorbidities in spondyloarthritis. Front Med (Lausanne). 2018;5:62. https://doi.org/10.3389/fmed.2018.00062
6. 6. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–281. https://doi.org/10.1056/NEJMra070553
7. 7. Aranow C. Vitamin D and the immune system. J Investig Med. 2011;59:881–886. https://doi.org/10.2310/JIM.0b013e31821b8755
8. 8. Cantorna MT, Snyder L, Lin Y-D, Yang L. Vitamin D and 1, 25(OH)2D regulation of T cells. Nutrients. 2015;7:3011–21. https://doi.org/10.3390/nu7043011

9. 9. Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients. 2013;5:2502–2521. https://doi.org/10.3390/nu5072502
10. 10. Athanassiou L, Kostoglou-Athanassiou I, Koutsilieris M, Shoenfeld Y. Vitamin D and Autoimmune Rheumatic Diseases. Biomolecules. 2023;13(4):709. https://doi.org/10.3390/ biom13040709
11. 11. Chen M, Li W, Li L, Yang Y, Pu X. Ankylosing spondylitis disease activity and serum vitamin D levels: A systematic review and meta-analysis. Medicine (Baltimore). 2022;101:e31764. https://doi.org/10.1097/MD.0000000000031764
12. 12. Cai G, Wang L, Fan D, Xin L, Liu L, Hu Y, et al. Vitamin D in ankylosing spondylitis: review and meta-analysis. Clin Chim Acta. 2015;438:316–322. https://doi.org/10.1016/j.cca.2014.08.040
13. 13. Kocyigit BF, Akyol A. Vitamin D levels in patients with ankylosing spondylitis: is it related to disease activity? Pak J Med Sci. 2018;34:1209–1214. https://doi.org/10.12669/pjms.345.15739
14. 14. Mermerci Baskan B, Pekin Dogan Y, Sivas F, Bodur H, Ozoran K. The relation between osteoporosis and vitamin D levels and disease activity in ankylosing spondylitis. Rheumatol Int. 2010;30:375–381. https://doi.org/10.1007/s00296-009-0975-7
15. 15. Lin J, Liu J, Davies ML, Chen W. Serum vitamin D level and rheumatoid arthritis disease activity: review and meta-analysis. PLoS One. 2016;11:e0146351. https://doi.org/10.1371/journal.pone.0146351
16. 16. Huang W, Shah S, Long Q, Crankshaw AK, Tangpricha V. Improvement of pain, sleep, and quality of life in chronic pain patients with vitamin D supplementation. Clin J Pain. 2013;29:341–347. https://doi.org/10.1097/AJP.0b013e318255655d
17. 17. Arends S, Spoorenberg A, Bruyn GA, Houtman PM, Leijsma MK, Kallenberg CGM, et al. The relation between bone mineral density, bone turnover markers, and vitamin D status in ankylosing spondylitis patients with active disease: a crosssectional analysis. Osteoporos Int. 2011;22:1431–1439. https://doi.org/10.1007/s00198-010-1338-7
18. 18. Braun J, Baraliakos X, Listing J, Sieper J. Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept. Arthritis Rheum. 2005;52:2447–2451. https://doi.org/10.1002/art.21197