Investigation of the Effect of Vitamin D On Multiple Sclerosis Patients Using Fingolimod

Yıl 2023, Cilt: 49 Sayı: 3, 297 - 303, 31.12.2023

Furkan Sarıdaş , Sarah Hamide Lazrak Emine Rabia Koç Ömer Faruk Turan

https://doi.org/10.32708/uutfd.1336618

Öz

Multiple Sclerosis (MS) is a chronic, inflammatory, and neurodegenerative disease of the central nervous system that begins in young adulthood. MS is the leading cause of non-traumatic disability in young adults. Vitamin D is known to have immunomodulatory properties, and its deficiency has been identified as an environmental risk factor for the development of MS and has been associated with disease activation. This study aimed to determine the effects of initial vitamin D levels and replacement on clinical and radiological outcome parameters of patients with MS diagnosed with fingolimod treatment. The medical records of 214 patients we followed up in our center for eight years were evaluated retrospectively. Vitamin level data were analyzed in 132 patients for pretreatment, 130 during treatment, and 98 for replacement therapy. Endpoints were radiological activation, annual attack rate, new attack, progression in EDSS, and no evidence of disease activity-3 (NEDA-3). No correlation was found between the initial vitamin D levels and clinical or radiological activation or progression of the disease in patients receiving fingolimod therapy. In patients with low vitamin levels, no difference was found in the outcome parameters of patients whose replacement therapy could not reach the desired values. No positive difference was observed when the subgroup with high disease activation was evaluated. In conclusion, no correlation was found between initial low serum vitamin D level or inadequate replacement and clinical and radiological worsening. However, there is a need for more comprehensive studies in which other risk factors and genetic polymorphisms specific to the Turkish population are evaluated.

Anahtar Kelimeler

multiple sclerosis, vitamin D, therapeutic treatment, fingolimod

D Vitamininin Fingolimod Tedavisi Alan Multipl Skleroz Hastaları Üzerine Etkisinin Araştırılması

Öz

Multipl skleroz (MS), genç erişkin yaşta başlayan merkezi sinir sisteminin kronik, inflamatuar ve nörodejeneratif bir hastalığıdır. MS genç yetişkinlerde travmatik olmayan sakatlığın önde gelen nedenidir. D vitamininin immünomodülatör özelliklere sahip olduğu bilinmektedir. Eksikliği MS gelişimi için çevresel bir risk faktörü olarak tanımlanmakta ve hastalık aktivasyonu ile ilişkilendirilmektedir. Bu çalışmanın amacı fingolimod tedavisi alan MS tanılı hastalarda başlangıç vitamin D düzeyleri ve replasman tedavisi ile hastalığın klinik ve radyolojik sonlanımı arasındaki ilişkiyi belirlemektir. 2015-2023 tarihleri arasında merkezimizde takip ettiğimiz 214 hastanın tıbbi kayıtları retrospektif değerlendirildi. Vitamin D düzeyi verileri tedavi öncesi için 132 ve replasman tedavisi için 98 hastada analiz edildi. Sonlanım parametreleri; radyolojik aktivasyon, yıllık atak oranı, yeni atak gelişmesi, Genişletilmiş Özürlülük Durum Ölçeği (EDSS)’nde progresyon ve hastalık aktivitesine dair kanıtın olmaması-3 (NEDA-3) olarak belirlendi. Fingolimod tedavisi başlangıcında vitamin D düzeyleri ile hastalığın klinik veya radyolojik aktivasyonu veya progresyonu ile herhangi bir ilişki saptanmadı. Vitamin düzeyi düşük olan hastalarda replasman tedavisi ile >30 μg/L sağlanamayan hastalarda belirlenen sonlanım parametlerinde farklılık saptanmadı. Yüksek hastalık aktivasyonu olan alt grup değerlendirildiğinde de olumlu yönde herhangi bir fark ve değişim gözlemlenmedi. Sonuç olarak başlangıçtaki düşük serum vitamin D düzeyi veya yetersiz replasmanı ile klinik ve radyolojik kötüleşme arasında ilişki saptanmadı. Ancak sonuçları etkileyebilecek diğer risk faktörlerinin ve türk popülasyonuna özgü genetik polimorfizmlerin de değerlendirildiği daha geniş kapsamlı çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

multipl skleroz, vitamin D, terapötik tedavi, fingolimod

Kaynakça

• 1. Sassi, F., C. Tamone, and P. D'Amelio, Vitamin D: Nutrient, Hormone, and Immunomodulator. Nutrients, 2018. 10(11).
• 2. Feige, J., et al., Vitamin D Supplementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats. Nutrients, 2020. 12(3).
• 3. Dobson, R. and G. Giovannoni, Multiple sclerosis - a review. Eur J Neurol, 2019. 26(1): p. 27-40.
• 4. Soilu-Hanninen, M., et al., A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon beta-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry, 2012. 83(5): p. 565-71.
• 5. Stein, M.S., et al., A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology, 2011. 77(17): p. 1611-8.
• 6. Murdaca, G., et al., Emerging role of vitamin D in autoimmune diseases: An update on evidence and therapeutic implications. Autoimmun Rev, 2019. 18(9): p. 102350.
• 7. Sellner, J., et al., The increasing incidence and prevalence of female multiple sclerosis--a critical analysis of potential environmental factors. Autoimmun Rev, 2011. 10(8): p. 495-502.
• 8. Hiremath, G.S., et al., Vitamin D status and effect of low-dose cholecalciferol and high-dose ergocalciferol supplementation in multiple sclerosis. Mult Scler, 2009. 15(6): p. 735-40.
• 9. Munger, K.L., et al., Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA, 2006. 296(23): p. 2832-8.
• 10. Gandhi, F., et al., Impact of Vitamin D Supplementation on Multiple Sclerosis. Cureus, 2021. 13(10): p. e18487.
• 11. Moosazadeh, M., et al., Vitamin D status and disability among patients with multiple sclerosis: a systematic review and meta-analysis. AIMS Neurosci, 2021. 8(2): p. 239-253.
• 12. Fatima, M., et al., Therapeutic Role of Vitamin D in Multiple Sclerosis: An Essentially Contested Concept. Cureus, 2022. 14(6): p. e26186.
• 13. Laursen, J.H., et al., Vitamin D supplementation reduces relapse rate in relapsing-remitting multiple sclerosis patients treated with natalizumab. Mult Scler Relat Disord, 2016. 10: p. 169-173.
• 14. Jelinek, G.A., et al., Latitude, sun exposure and vitamin D supplementation: associations with quality of life and disease outcomes in a large international cohort of people with multiple sclerosis. BMC Neurol, 2015. 15: p. 132.
• 15. Glabska, D., et al., Vitamin D Supplementation and Mental Health in Multiple Sclerosis Patients: A Systematic Review. Nutrients, 2021. 13(12).
• 16. Mansoor, F., et al., Association Between Serum Vitamin D Levels and Frequency of Relapses in Patients With Multiple Sclerosis. Cureus, 2021. 13(4): p. e14383.
• 17. Vandebergh, M., B. Dubois, and A. Goris, Effects of Vitamin D and Body Mass Index on Disease Risk and Relapse Hazard in Multiple Sclerosis: A Mendelian Randomization Study. Neurol Neuroimmunol Neuroinflamm, 2022. 9(3).
• 18. Wesnes, K., et al., Low vitamin D, but not tobacco use or high BMI, is associated with long-term disability progression in multiple sclerosis. Mult Scler Relat Disord, 2021. 50: p. 102801.
• 19. Piedel, F., et al., Correlation between vitamin D and alterations in MRI among patients with multiple sclerosis. Ann Agric Environ Med, 2021. 28(3): p. 372-377.
• 20. Martinez-Lapiscina, E.H., et al., Associations of serum 25(OH) vitamin D levels with clinical and radiological outcomes in multiple sclerosis, a systematic review and meta-analysis. J Neurol Sci, 2020. 411: p. 116668.
• 21. Akhtar, A., et al., Radiological Association Between Multiple Sclerosis Lesions and Serum Vitamin D Levels. Cureus, 2022. 14(11): p. e31824.
• 22. Ferre, L., et al., Basal vitamin D levels and disease activity in multiple sclerosis patients treated with fingolimod. Neurol Sci, 2018. 39(8): p. 1467-1470.
• 23. Hausler, D., et al., High dose vitamin D exacerbates central nervous system autoimmunity by raising T-cell excitatory calcium. Brain, 2019. 142(9): p. 2737-2755.
• 24. Hashemi, R., et al., The impact of vitamin D3 intake on inflammatory markers in multiple sclerosis patients and their first-degree relatives. PLoS One, 2020. 15(4): p. e0231145.
• 25. Walawska-Hrycek, A., et al., The Impact of Vitamin D Low Doses on Its Serum Level and Cytokine Profile in Multiple Sclerosis Patients. J Clin Med, 2021. 10(13).
• 26. Zorzella-Pezavento, S.F.G., et al., Is there a window of opportunity for the therapeutic use of vitamin D in multiple sclerosis? Neural Regen Res, 2022. 17(9): p. 1945-1954.
• 27. Hanninen, K., et al., Vitamin D supplementation and serum neurofilament light chain in interferon-beta-1b-treated MS patients. Brain Behav, 2020. 10(9): p. e01772.
• 28. Smolders, J., et al., Vitamin D(3) supplementation and neurofilament light chain in multiple sclerosis. Acta Neurol Scand, 2020. 141(1): p. 77-80.
• 29. Shaygannejad, V., et al., Effects of adjunct low-dose vitamin d on relapsing-remitting multiple sclerosis progression: preliminary findings of a randomized placebo-controlled trial. Mult Scler Int, 2012. 2012: p. 452541.
• 30. Zheng, C., et al., The efficacy of vitamin D in multiple sclerosis: A meta-analysis. Mult Scler Relat Disord, 2018. 23: p. 56-61.
• 31. Hanaei, S., et al., Effect of Vitamin D Supplements on Relapse Rate and Expanded Disability Status Scale (EDSS) in Multiple Sclerosis (MS): A Systematic Review and Meta-Analysis. Int J Prev Med, 2021. 12: p. 42.
• 32. Wasnik, S., et al., Vitamin D as a Potential Therapy for Multiple Sclerosis: Where Are We? Int J Mol Sci, 2020. 21(9).
• 33. Rotstein, D.L., et al., Effect of vitamin D on MS activity by disease-modifying therapy class. Neurol Neuroimmunol Neuroinflamm, 2015. 2(6): p. e167.
• 34. Garcia-Gil, M., et al., Crosstalk between sphingolipids and vitamin D3: potential role in the nervous system. Br J Pharmacol, 2017. 174(8): p. 605-627.
• 35. Miele, G., et al., Association of vitamin D serum levels andvitamin D supplementation with B cell kinetics and disease activity in Multiple Sclerosis patients treated with ocrelizumab: an Italian multi-center study. Mult Scler Relat Disord, 2022. 68: p. 104395.
• 36. Fichna, M., et al., Association of the CYP27B1 C(-1260)A polymorphism with autoimmune Addison's disease. Exp Clin Endocrinol Diabetes, 2010. 118(8): p. 544-9.
• 37. Cortese, M., et al., Vitamin D, smoking, EBV, and long-term cognitive performance in MS: 11-year follow-up of BENEFIT. Neurology, 2020. 94(18): p. e1950-e1960.
• 38. Hongell, K., et al., Efficacy and safety outcomes in vitamin D supplement users in the fingolimod phase 3 trials. J Neurol, 2018. 265(2): p. 348-355.