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Lower concentration of vitamin D is associated with lower DAS28 and VAS-pain scores in patients with inflammatory rheumatic diseases treated with infliximab: a pilot study

  • Observational Research
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Abstract

Vitamin D is beneficial in patients with immune-mediated rheumatic diseases as it has been shown that it lowers the incidence risk and the level of inflammation. To examine the association between clinical outcomes and initial 25-hydroxyvitamin D [25(OH)D] concentrations in patients with the immune-mediated rheumatic diseases treated with infliximab for 9 months. This study was performed in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) treated with infliximab for at least 38 weeks. Disease activity was assessed using Disease Activity Score (DAS28) for RA and PsA and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS, while the global assessment was performed using the Visual Analogue Scale (VAS). Patients were divided into 2 groups according to 25(OH)D concentration which was classified as deficient or non-deficient (below and above 50 nmol/L, respectively). Concentrations of infliximab (IFX) and C-reactive protein (CRP) were measured according to the manufacturer’s instructions.This study was performed in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) treated with infliximab for at least 38 weeks. Disease activity was assessed using Disease Activity Score (DAS28) for RA and PsA and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS, while the global assessment was performed using the Visual Analogue Scale (VAS). Patients were divided into 2 groups according to 25(OH)D concentration which was classified as deficient or non-deficient (below and above 50 nmol/L, respectively). Concentrations of infliximab (IFX) and C-reactive protein (CRP) were measured according to the manufacturer’s instructions. The study included 23 patients (14 with RA, 6 with AS and 3 with PsA), median age 54 years, 15 females. Vitamin D deficient and non-deficient groups had median initial concentrations of 38 and 61 nmol/L, respectively. DAS28 and pain on VAS calculated at the 2nd and 38th week showed a statistically significant decrease only in RA and PsA patients with vitamin D deficiency (P = 0.02 and 0.06, respectively). Lower initial concentration of 25(OH)D in patients treated with infliximab was associated with better improvement of clinical measures (DAS28 and VAS) of disease after 9 months of therapy.

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References

  1. Jokar M, Jokar M (2018) Prevalence of Inflammatory Rheumatic Diseases in a Rheumatologic outpatient clinic: analysis of 12626 cases. Rheum Res 3(1):21–27

    Article  Google Scholar 

  2. Smolen JS, Landewé R, Bijlsma J (2020) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. https://doi.org/10.1136/annrheumdis-2019-216655

    Article  PubMed  PubMed Central  Google Scholar 

  3. Silva LC, Ortigosa LC, Benard G (2010) Anti-TNF-α agents in the treatment of immune-mediated inflammatory diseases: mechanisms of action and pitfalls. Immunotherapy 2(6):817–833

    Article  CAS  PubMed  Google Scholar 

  4. Mezones-Holguin E, Gamboa-Cardenas RV, Sanchez-Felix G, Chávez-Corrales J, Helguero-Santin LM, Laban Seminario LM, Burela-Prado PA, Castro-Reyes MM, Fiestas F (2019) Efficacy and safety in the continued treatment with a biosimilar drug in patients receiving infliximab: a systematic review in the context of decision-making from a Latin-American Country. Front Pharmacol 10:1010

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kamata M, Tada Y (2020) Efficacy and safety of biologics for psoriasis and psoriatic arthritis and their impact on comorbidities: a literature review. Int J Mol Sci 21(5):1690

    Article  PubMed Central  Google Scholar 

  6. Liu W, Wu YH, Zhang L, Liu XY, Xue B, Liu B, Wang Y, Ji Y (2016) Efficacy and safety of TNF-α inhibitors for active ankylosing spondylitis patients: multiple treatment comparisons in a network meta-analysis. Sci Rep 6:32768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Moreno M, Gratacós J, Torrente-Segarra V, Sanmarti R, Morlà R, Pontes C, Llop M, Juanola X; REMINEA study Group (2019) Withdrawal of infliximab therapy in ankylosing spondylitis in persistent clinical remission, results from the REMINEA study. Arthritis Res Ther 21(1):88

    Article  Google Scholar 

  8. Buch MH, Seto Y, Bingham SJ, Bejarano V, Bryer D, White J, Emery P (2005) C-reactive protein as a predictor of infliximab treatment outcome in patients with rheumatoid arthritis: defining subtypes of nonresponse and subsequent response to etanercept. Arthritis Rheum 52(1):42–48

    Article  CAS  PubMed  Google Scholar 

  9. Franco AS, Freitas TQ, Bernardo WM, Pereira RMR (2017) Vitamin D supplementation and disease activity in patients with immune-mediated rheumatic diseases: a systematic review and meta-analysis. Medicine (Baltimore) 96(23):e7024

    Article  CAS  Google Scholar 

  10. Holick MF, Binkley NC, Bischoff-Ferrari HA et al (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:1911–1930

    Article  CAS  PubMed  Google Scholar 

  11. Heidari B, Hajian-Tilaki K, Babaei M (2019) Vitamin D deficiency and rheumatoid arthritis: epidemiological, immunological, clinical and therapeutic aspects. Mediterr J Rheumatol 30(2):94–102

    PubMed  PubMed Central  Google Scholar 

  12. Aslam MM, John P, Bhatti A, Kamboh MI (2019) Vitamin D as a principal factor in mediating rheumatoid arthritis-derived immune response. Biomed Res Int 2019:3494937

    Article  PubMed  PubMed Central  Google Scholar 

  13. Lin J, Liu J, Davies ML, Chen W (2016) Serum vitamin D level and rheumatoid arthritis disease activity: review and meta-analysis. PLoS ONE 11:e0146351

    Article  PubMed  PubMed Central  Google Scholar 

  14. Reich KM, Fedorak RN, Madsen K, Kroeker KI (2016) Role of vitamin D in infliximab-induced remission in adult patients with Crohn's disease. Inflamm Bowel Dis 22(1):92–99

    Article  PubMed  Google Scholar 

  15. World Medical Association (2013) World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310(20):2191–2194

    Article  Google Scholar 

  16. van Riel PL, Renskers L (2016) The Disease Activity Score (DAS) and the Disease Activity Score using 28 joint counts (DAS28) in the management of rheumatoid arthritis. Clin Exp Rheumatol 34(5 Suppl 101):S40–S44

    PubMed  Google Scholar 

  17. Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A (1994) A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 21(12):2286–2291

    CAS  PubMed  Google Scholar 

  18. van der Heijde D, Ramiro S, Landewé R et al (2017) 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis 76(6):978–991

    Article  Google Scholar 

  19. Cohen JD, Cunin P, Farrenq V, Oniankitan O, Carton L, Chevalier X, Claudepierre P (2006) Estimation of the Bath Ankylosing Spondylitis Disease Activity Index cutoff for perceived symptom relief in patients with spondyloarthropathies. J Rheumatol 33:79–81

    PubMed  Google Scholar 

  20. Ross AC, Manson JE, Abrams SA et al (2011) The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96(1):53–58

    Article  CAS  PubMed  Google Scholar 

  21. Nikolac Gabaj N, Unic A, Miler M, Pavicic T, Culej J, Bolanca I, Herman Mahecic D, Milevoj Kopcinovic L, Vrtaric A (2020) In sickness and in health: pivotal role of vitamin D. Biochem Med (Zagreb) 30(2):020501

    Article  Google Scholar 

  22. Bartley J (2010) Vitamin D: emerging roles in infection and immunity. Expert Rev Anti Infect Ther 8:1359–1369

    Article  CAS  PubMed  Google Scholar 

  23. Bikle DD (2011) Vitamin D regulation of immune function. Vitam Horm 86:1–21

    Article  CAS  PubMed  Google Scholar 

  24. Jankosky C, Deussing E, Gibson RL, Haverkos HW (2012) Viruses and vitamin D in the etiology of type 1 diabetes mellitus and multiple sclerosis. Virus Res 163(2):424–430

    Article  CAS  PubMed  Google Scholar 

  25. Kim H, Baek S, Hong SM, Lee J, Jung SM, Lee J, Cho M, Kwok SK, Park SH (2020) 1,25-dihydroxy Vitamin D3 and Interleukin-6 Blockade Synergistically Regulate Rheumatoid Arthritis by Suppressing Interleukin-17 Production and Osteoclastogenesis. J Korean Med Sci 35(6):e40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Grazio S, Naglić ĐB, Anić B et al (2015) Vitamin D serum level, disease activity and functional ability in different rheumatic patients. Am J Med Sci 349(1):46–49

    Article  PubMed  Google Scholar 

  27. Cutolo M, Otsa K, Laas K et al (2006) Circannual vitamin d serum levels and disease activity in rheumatoid arthritis: Northern versus Southern Europe. Clin Exp Rheumatol 24(6):702–704

    CAS  PubMed  Google Scholar 

  28. Vojinovic J, Tincani A, Sulli A et al (2017) European multicentre pilot survey to assess vitamin D status in rheumatoid arthritis patients and early development of a new Patient Reported Outcome questionnaire (D-PRO). Autoimmun Rev 16(5):548–554

    Article  CAS  PubMed  Google Scholar 

  29. Mukherjee D, Lahiry S, Thakur S, Chakraborty DS (2019) Effect of 1,25 dihydroxy vitamin D3 supplementation on pain relief in early rheumatoid arthritis. J Family Med Prim Care 8(2):517–522

    Article  PubMed  PubMed Central  Google Scholar 

  30. Peterson CA, Heffernan ME (2008) Serum tumor necrosis factor-alpha concentrations are negatively correlated with serum 25 (OH) D concentrations in healthy women. J Inflamm 5:10

    Article  Google Scholar 

  31. Fransen J, Antoni C, Mease PJ et al (2006) Performance of response criteria for assessing peripheral arthritis in patients with psoriatic arthritis: analysis of data from randomized controlled trials of two tumor necrosis factor inhibitors. Ann Rheum Dis 65:1373–1378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Pollard LC, Kingsley GH, Choy EH, Scott DL (2010) Fibromyalgic rheumatoid arthritis and disease assessment. Rheumatology 49:924–928

    Article  PubMed  Google Scholar 

  33. Elizondo-Montemayor L, Castillo EC, Rodríguez-López C et al (2017) Seasonal variation in vitamin D in association with age, inflammatory cytokines, anthropometric parameters, and lifestyle factors in older adults. Mediators Inflamm 2017:5719461

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

There are no financial conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Clinical Chemistry, Sestre Milosrdnice University Hospital Center, Vinogradska 29, Zagreb, Croatia

    Marijana Miler, Nora Nikolac Gabaj, Antonio Vahtarić, Alen Vrtarić & Nada Vrkić

  2. Department for Rheumatology, Physical and Rehabilitation Medicine, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia

    Simeon Grazio, Frane Grubišić, Hana Skala Kavanagh & Ines Doko Vajdić

Authors
  1. Marijana Miler
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  2. Nora Nikolac Gabaj
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  3. Simeon Grazio
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  4. Antonio Vahtarić
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  5. Alen Vrtarić
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  6. Frane Grubišić
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  7. Hana Skala Kavanagh
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  8. Ines Doko Vajdić
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  9. Nada Vrkić
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Contributions

In the study conception and design contributed MM, NNG and NV. The first draft of the manuscript was written by MM. All authors commented on the first version. Patient’s acquisition and expert assessment of eligible patients: SG, FG, HSK, IDV. All methods included in the manuscript were performed by AV and AV. Data analysis was done by MM, NNG, SG and NV. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Marijana Miler.

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Ethical approval

The study was designed in accordance with the Declaration of Helsinki and was approved by the Ethical Committee of the Sestre milosrdnice University Hospital Center.

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Miler, M., Nikolac Gabaj, N., Grazio, S. et al. Lower concentration of vitamin D is associated with lower DAS28 and VAS-pain scores in patients with inflammatory rheumatic diseases treated with infliximab: a pilot study. Rheumatol Int 40, 1455–1461 (2020). https://doi.org/10.1007/s00296-020-04607-3

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  • DOI: https://doi.org/10.1007/s00296-020-04607-3

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