Sühan TAŞKIN, Zeynep ALPOĞUZ, Mehmet Onat ÇAKIT, Melek AYKUT SELÇUK, Burcu DUYUR ÇAKIT, Hakan GENÇ

HLA-B27 POZİTİFLİĞİNİN ERKEK ANKİLOZAN SPONDİLİT HASTALARINDA ANTİ-TNF TEDAVİ CEVABINA ETKİLERİ

Amaç: Anti-TNF tedavi alan erkek Ankilozan Spondilit (AS) hastalarında HLA-B27 pozitifliğinin anti-TNF tedavi etkinliği üzerindeki olası etkilerini araştırmaktır.. Materyal ve Metod:Bir yıldır anti-TNF tedavi alan 30 erkek AS hastasının verileri retrospektif olarak incelendi. Hastaların kullandığı anti-TNF tedavi ajanları, demografik veriler ve laboratuvar aktivite parametreleri kaydedildi. Hastaların ağrı düzeyleri Vizüel Analog Skala (VAS), Hastalık aktivitesi Bath ankilozan spondilit hastalık aktivite indeksi (BASHAI), fonksiyonel durum Bath ankilozan spondilit fonksiyon indeksi (BASFİ) ile değerlendirildi. Hastalar HLA-B27 (+) ve (-) olmak üzere 2 gruba ayrıldı ve hastalık aktivite ve fonksiyon parametreleri karşılaştırıldı. Bulgular: Retrospektif analize dahil edilen 30 erkek AS hastasının 11’inde HLA-B27 (+)’ti. HLA-B27 (+) hastaların yaş ortalamaları 38.18±8.18 yıl, HLA-B27 (-) hastaların yaş ortalamaları 40.57±5.89 yıldı. Grupların yaş ortalamaları açısından istatistiksel anlamlı fark yoktu (p>0.05). Ortalama hastalık süreleri açısından gruplar arasında fark yoktu (HLA-B27 (+) :15.9±7.4 yıl, HLA-B27 (-): 15.89±4.71 yıl, p>0.05). Grupların başlangıç ortalama BASHAI (HLA-B27 (+):6.15±1.41, negatif: 6.72±1.1) ve BASFİ (HLA-B27 (+) :5.59±1.9, HLA-B27(-) : 5.97±1.49) değerleri arasında da istatistiksel olarak anlamlı farklılık tespit edilmedi (p>0.05). Gruplar BASHAI ile bakılan hastalık aktivitesi açısından karşılaştırıldığında HLA-B27 pozitifliğinin 1. yıl anti-TNF etkinliğine belirgin etkisi saptanmadı (p>0.05). Bununla beraber HLA-B27 (+) hastalarda anti-TNF tedavi ile 1.yılda BASFİ ile değerlendirilen fonksiyonel parametrelerin daha belirgin olarak düzeldiği tespit edildi (p=0.016). Sonuç: HLA-B27 (+) AS hastalarında anti-TNF tedavi HLA-B27 (-) hastalara göre fonksiyonel parametrelerde 1 yılda belirgin düzelme sağladığı gözlendi. Bununla birlikte HLA-B27 pozitifliğinin AS’li hastalarda anti-TNF tedavisi ile elde edilen hastalık aktivite azalması üzerinde belirgin fark yaratmadığı gözlendi.

Anahtar Kelimeler:

ankilozan spondilit, anti-tnf, tedavi, HLA B27

PDF

___

1. Deodhar A, Yu D. Switching tumor necrosis factor inhibitors in the treatment of axial spondyloarthritis. Semin Arthritis Rheum 2017;47(3):343-350.
2. Stolwijk C, Boonen A, vanTubergen A, Reveille JD. Epidemiology of spondyloarthritis. Rheum Dis Clin North Am 2012;38:441–76.
3. Rudwaleit M, vanderHeijde D, Landewé R, Listing J, Akkoc N, Brandt J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009;68:777–83.
4. Ward MM, Deodhar A, Akl EA, Lui A, Ermann J, Gensler LS, et al. American College of Rheumatology / Spondylitis Association of America / Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol 2016;68:282–98.
5. Braun J, Baraliakos X, Heldmann F, Kiltz U. Tumor necrosis factor alpha antagonists in the treatment of axial spondyloarthritis. Expert Opin Investig Drugs 2014;23:647–59.
6. Lie E, vander Heijde D, Uhlig T, Mikkelsen K, Rødevand E, Koldingsnes W, etal. Effectiveness of switching between TNF inhibitors in ankylosing spondylitis: data from the NOR-DMARD register. Ann Rheum Dis 2011;70:157–63.
7. Brandt J, Khariouzov A, Listing J, et al. Six-month results of a double-blind, placebo-controlled trial of etanercept treatment in patients with active ankylosing spondylitis. Arthritis Rheum 2003;48:1667–75.
8. Landewe R, Braun J, Deodhar A, et al. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study. Ann Rheum Dis 2014;73:39–47.
9. Kristensen LE, Kapetanovic MC, Gulfe A, et al. Predictors of response to anti-TNF therapy according to ACR and EULAR criteria in patients with established RA: results from the South Swedish Arthritis Treatment Group Register. Rheumatology (Oxford) 2008;47:495–9.
10. Mancarella L, Bobbio-Pallavicini F, Ceccarelli F, et al; GISEA group. Good clinical response, remission, and predictors of remission in rheumatoid arthritis patients treated with tumor necrosis factor-alpha blockers: the GISEA study. J Rheumatol 2007;34:1670–3.
11. Maneiro JR(1), Souto A(1), Salgado E(1), Mera A(2), Gomez-Reino JJ(2). Predictors of response to TNF antagonists in patients with ankylosing spondylitis and psoriatic arthritis: systematic review and meta-analysis. RMD Open 2015;1(1):e000017.
12. Rudwaleit M, Vanden Bosch F, Kron M, Kary S, Kupper H. Effectiveness and safety of adalimumab in patients with ankylosing spondylitis or psoriatic arthritis and history of anti-tumor necrosis factor therapy. Arthritis Res Ther 2010;12:R117. 13. Paccou J, Baclé-Boutry M, Solau-Gervaıs E, Bele-Philippe P, Flipo R. Dosage adjustment of anti-tumor necrosis factor-α inhibitor in ankylosing spondylitis is effective in maintaining remission in clinical practice. J Rheumatol 2012;39;1418-1423.
14. Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984;27:361-8.
15. Ay S, Kutlay Ş, Kurtaiş Y, Yanık B. Adaptation and validation of the Turkish version of the Bath ankylosing spondylitis disease activity index (BASDAI). Arch of Rheum 2004;19(3):139-146.
16. Yanık B, Gürsel YK, Kutlay S, Ay S, Elhan AH. Adaptation of the Bath Ankylosing Spondylitis Functional Index to the Turkish population, its reliability and validity: functional assessment in AS. Clin Rheumatol 2005;24(1):41-7.
17. Evans DM, Spencer CC, Pointon JJ, Su Z, Harvey D, Kochan G, Oppermann U et al. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat Genet 2011;43(8):761-7.
18. Chen B, Li J, He C, Li D, Tong W, Zou Y, Xu W. Role of HLA-B27 in the pathogenesis of ankylosing spondylitis. Mol Med Rep 2017;15(4):1943–1951.
19. Chen X, Zhou X, Li X, Tang J, Hu X, Wang J, Xu C. Effects of tumor necrosis factor inhibitor on serum level of HLA-B27 and PDCD-1 in patients with ankylosing spondylitis. Cell Biochem Biophys 2014;70(2):1453-7.
20. Brewerton DA, Hart FD, Nicholls A, Caffrey M, James DC, Sturrock RD. Ankylosing spondylitis and HL-A 27. Lancet 1973;1(7809):904-7.
21. Rudwaleit M, Claudepierre P, Wordsworth P, Cortina EL, Sieper J, Kron M et al. Effectiveness, safety and predictors of good clinical response in 1250 patients treated with adalimumab for active ankylosing spondylitis. J Rheumatol 2009;36:801-808.
22. Baraliakos X, Koenig AS, Jones H, Szumski A, Collier D, Bananis E. Predictors of Clinical Remission under Anti-tumor Necrosis Factor Treatment in Patients with Ankylosing Spondylitis: Pooled Analysis from Large Randomized Clinical Trials. J Rheumatol 2015;42(8):1418-26.
23. Rudwaleit M, Listing J, Brandt J, Braun J, Sieper J. Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor α blockers in ankylosing spondylitis. Ann Rheum Dis 2004;63:665-670.
24. Landewe R, Dougados M, Mielants H, van der Tempel H, ven der Heijde D. Physical function in ankylosing spondylitis is independently determined by both disease activity and radiographic damage of the spine. Ann Rheum Dis 2009;68:863-867.
25. Braun J, Brandt J, Listing J, Zink A, Alten R, Golder W et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet 2002;359:1187-93.
26. Maxwell LJ, Zochling J, Boonen A, Singh JA, Veras MM, Tanjong Ghogomu E, Benkhalti Jandu M, Tugwell P, Wells GA. TNF-alpha inhibitors for ankylosing spondylitis. Cochrane Database Syst Rev 2015;18(4):CD005468.