EFFECTS OF SMOKING IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS RECEIVING TUMOR NECROSIS FACTOR INHIBITORS THERAPY

Öz

Objective: The aim of this study was to examine the impact of smoking on axial spondyloarthritis (axSpA) patients taking tumor necrosis factor inhibitors (TNFi).
Material and Method: Our study consisted of 211 patients who were diagnosed with axSpA and received TNFi treatment in the rheumatology outpatient clinic. The patients were evaluated retrospectively, cross-sectionally and grouped by intensity of smoking (pack-years). Those who smoked>20 pack-years were defined as heavy smokers. Groups were compared in terms of physical examination, laboratory values and disease evaluation indexes (Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylos- ing Spondylitis Quality of Life (ASQoL) and Beck Depression In- ventory (BDI) scores. Mann-Whitney U and Spearman correlation analysis tests were used for data analysis
Results: Comparison of the smoker (n=121) and non-smoker groups (n=90) revealed BASMI was lower in the non-smoker group (p=0.04). Smoking intensity correlated with BDI (r=0.323, p<0.001), BASDAI (r=0.257, p=0.005), BASMI components (lomber lateral flexion (LLF) (r=-0.303, p=0.001), cervical rotation (CR) (r=-0.232, p=0.012), and tragus wall distance (TWD) (r=0.27, p=0.003)). Multivariate analysis revealed an association between the pack-years of smoking and the BASMI [regression coefficient (B)=0.067, standard error (SE)=0.22, 95%CI=0.02, 0.10; p=0.003], baseline (B=pretreatment)-last value (L.=posttreatment) difference of BASFI [B=-0.063, SE=0.02, 95%CI=-0.10, -0.20; p=0.003], of BASDAI [B=-0.047, SE=0.02, 95%CI=-0.08, -0.007; p=0.026], ASQoL [B=-0.125, SE=0.04, 95%CI=0.04, -0.20; p=0.003]. In heavy smokers, significant worsening was found in LLFL (p=0.01), CRL (p=0.04), TWDL (p=0.001), BASFIL (p=0.035) and BASMIL (p=0.001). Significant differences were found in the baseline (B) and last (L) BASDAI (p=0.042), BASFIL (p=0.002), BASFIB-L (p=0.07) and BASMI (p=0.03) values in the nonradiograpic-axSpA group in heavy smokers, compared to the AS group.
Conclusion: Our study showed that smoking, especially heavy smoking, has a negative effect in every phase of axSpA. Smok- ing intensity may correlate with reduced response to TNFi.
Keywords: Axial spondyloarthritis, ankylosing spondylitis, non-radiographic axial spondyloarthiris, tumor necrosis factor inhibitor therapy, smoking

Anahtar Kelimeler

• Axial spondyloarthritis
• ankylosing spondylitis
• non-radiographic axial spondyloarthiris
• tumor necrosis factor inhibitor therapy
• smoking

TÜMÖR NEKROZİS FAKTÖR İNHİBİTÖRÜ TEDAVİSİ ALAN AKSİYAL SPONDİLOARTRİTLİ HASTALARDA SİGARANIN ETKİLERİ

Öz

Amaç: Bu çalışma tümör nekrozis faktör alfa inhibitörü (TNFi) alan aksiyal spondiloartrit (axSpA) hastalarında sigaranın etkisini değerlendirme amacıyla yapıldı.
Gereç ve Yöntem: Çalışmamıza Romatoloji polikliniğinde axSpA tanısıyla tümör nekroz faktör alfa (TNFα) inhibitörü tedavisi alan 211 hasta alındı. Hastalar retrospektif, kesitsel olarak değerlendirildi ve sigara içme yoğunluğuna (paket-yıl) göre gruplandırıldı. Sigarayı >20 paket yıl üzerinde içenler ağır içiçi olarak tanımlandı. Gruplar fizik muayene ölçümleri, laboratuar ve hastalık değerlendirme indeksleri (Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) ve Ankylosing Spondylitis Quality of Life (ASQoL) ve Beck Depression Inventory (BDI)) ile karşılaştırıldı. Verilerin analizinde Mann-Whitney U ve Spearman korelasyon analizi testleri kullanıldı.
Bulgular: Sigara içen (n=121) ve içmeyen (n=90) grup karşılaştırıldığında BASMI sigara içmeyen grupta düşük bulunmuştur (p=0,04). Sigara içme yoğunluğu ile yapılan korelasyon analizinde BDI (r=0,323, p<0,001), BASDAI (r=0,257, p=0,005) ve BASMI bileşenleri (lomber lateral fleksiyon (LLF) (r=- 0,303, p=0,001) bulunmuştur. Multiple lineer regresyon analizinde sigara paket-yılı ile BASMI [regresyon katsayısı (B)=0,067, standart hata (SE)=0,22, %95CI=0,02, 0,10; p=0,003], BASFI’nin başlangıç (B=tedavi öncesi) ve son değeri (L=tedavi sonrası) arasındakifarkı [B=-0,063, SE=0,02, %95CI=-0,10, -0,20; p=0,003], BASDAI [B=-0.047, SE=0,02, %95CI=-0,08, -0,007; p=0,026] ve ASQoL [B=-0,125, SE=0,04, %95CI=0,04, -0,20; p=0,003] arasında ilişki saptandı. Ağır sigara içicilerinde LLFL (p=0,01),CRL (p=0,04), TWDL (p=0,001), BASFIL (p=0,035) ve BASMIL (p=0,001)’de anlamlı kötüleşme bulundu. Nonradyografik-axSpA grubunda ağır içicilerde AS grubuna göre BASDAIB-L (p=0,042), BASFIL (p=0,002), BASFIB-L (p=0,07) ve BASMI (p=0,03) değerlerinde anlamlı farklılıklar saptandı.
Sonuç: Çalışmamız sigara kullanımının özellikle sigara içme yo- ğunluğunun axSpA’nın her döneminde olumsuz etkisi olduğu göstermiştir. Sigara içme yoğunluğu, TNFi’ye verilen yanıtın azal- masıyla ilişkili olabilir.

Anahtar Kelimeler

• Aksiyal spondiloartrit
• ankilozan spondilit
• non-radyografik aksiyal spondiloartrit
• tümör nekrozis faktör inhi- bitörü tedavisi
• sigara

Kaynakça

1. 1. Sieper J, Rudwaleit M, Baraliakos X, Brandt J, Braun J, Burgos-Vargas R, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis 2009;68(Suppl 2):ii1-ii44. [CrossRef] google scholar
2. 2. Doran MF, Brophy S, MacKay K, Taylor G, Calin A. Predictors of long-term outcome in ankylosing spondylitis. J Rheumatol 2003;30(2):316-20. google scholar
3. 3. Ward MM, Weisman MH, Davis JC Jr, Reveille JD. Risk factors for functional limitations in patients with long-standing ankylosing spondylitis. Arthritis Rheum 2005;53(5):710-7. [CrossRef] google scholar
4. 4. Wendling D, Prati C. Spondyloarthritis and smoking: towards a new insight into the disease. Expert Rev ClinImmunol 2013;9(6):511-6. [CrossRef] google scholar
5. 5. Roelsgaard IK, Esbensen BA, 0stergaard M, Rollefstad S, Semb AG, Christensen R, et al. Smoking cessation intervention for reducing disease activity in chronic autoimmune inflammatory joint diseases. Cochrane Database Syst Rev 2019;9(9):CD012958. [CrossRef] google scholar
6. 6. Klareskog L, Padyukov L, Alfredsson L. Smoking as a trigger for inflammatory rheumatic diseases. Curr Opin Rheumatol 2007;19(1):49-54. [CrossRef] google scholar
7. 7. Chen CH, Chen HA, Lu CL, Liao HT, Liu CH, Tsai CY, et al. Association of cigarette smoking with Chinese ankylosing spondylitis patients in Taiwan: a poor disease outcome in systemic inflammation, functional ability, and physical mobility. Clin Rheumatol 2013;32(5):659-63. [CrossRef] google scholar
8. 8. Averns HL, Oxtoby J, Taylor HG, Jones PW, Dziedzic K, Dawes PT. Smoking and outcome in ankylosing spondylitis. Scand J Rheumatol 1996;25(3):138-42. [CrossRef] google scholar

9. 9. Kaan U, Ferda O. Evaluation of clinical activity and functional impairment in smokers with ankylosing spondylitis. Rheumatol Int 2005;25(5):357-60. [CrossRef] google scholar
10. 10. Chung HY, Machado P, van der Heijde D, D’Agostino MA, Dougados M. Smokers in early axial spondyloarthritis have earlier disease onset, more disease activity, inflammation and damage, and poorer function and health-related quality of life: results from the DESIR cohort. Ann Rheum Dis 2012;71(6):809-16. [CrossRef] google scholar
11. 11. Sakellariou GT, Anastasilakis AD, Kenanidis E, Potoupnis M, Tsiridis E, Savvidis M, et al. The effect of smoking on clinical and radiographic variables, and acute phase reactants in patients with ankylosing spondylitis. Rheumatol Int 2015;35(12):2109-14. [CrossRef] google scholar
12. 12. Poddubnyy D, Haibel H, Listing J, Mârker-Hermann E, Zeidler H, et al. Baseline radiographic damage, elevated acute-phase reactant levels, and cigarette smoking status predict spinal radiographic progression in early axial spondylarthritis. Arthritis Rheum 2012;64(5):1388-98. [CrossRef] google scholar
13. 13. Saevarsdottir S, Wedren S, Seddighzadeh M, Bengtsson C, Wesley A, Lindblad S, et al. Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment with methotrexate and tumor necrosis factor inhibitors: observations from the Epidemiological Investigation of Rheumatoid Arthritis and the Swedish Rheumatology Register cohorts. Arthritis Rheum 2011;63(1):26-36. [CrossRef] google scholar
14. 14. Ciurea A, Scherer A, Weber U, Exer P, Bernhard J, Tamborrini G, et al. Impaired response to treatment with tumour necrosis factor a inhibitors in smokers with axial spondyloarthritis. Ann Rheum Dis 2016;75(3):532-39. [CrossRef] google scholar
15. 15. Glintborg B, H0jgaard P, Lund Hetland M, Steen Krogh N, Kollerup G, Jensen J, et al. Impact of tobacco smoking on response to tumour necrosis factor-alpha inhibitor treatment in patients with ankylosing spondylitis0: results from the Danish nationwide DANBIO registry. Rheumatology (Oxford) 2016;55(4):659-68. [CrossRef] google scholar
16. 16. Zhao SS, Yoshida K, Jones GT, Hughes DM, Tedeschi SK, Lyu H, et al. Impact of Smoking in Response to Tumor Necrosis Factor Inhibitors in Axial Spondyloarthritis: Methodologic Considerations for Longitudinal Observational Studies. Arthritis Care Res (Hoboken) 2020;72(4):591-9. [CrossRef] google scholar
17. 17. Kydd AS, Chen JS, Makovey J, Chand V, Henderson L, Buchbinder R, et al. Smoking did not modify the effects of anti-TNF treatment on health-related quality of life among Australian ankylosing spondylitis patients. Rheumatology (Oxford). 2015;54(2):310-7. [CrossRef] google scholar
18. 18. Villaverde-Garcıa V, Cobo-Ibânez T, Candelas-Rodrîguez G, Seoane-Mato D, Campo-Fontecha PDD, Guerra M, et al. The effect of smoking on clinical and structural damage in patients with axial spondyloarthritis: A systematic literature review. Semin Arthritis Rheum 2017;46(5):569-83. [CrossRef] google scholar
19. 19. Zhang S, Li Y, Xu X, Feng X, Yang D, Lin G. Effect of cigarette smoking and alcohol consumption on disease activity and physical functioning in ankylosing spondylitis: a cross-sectional study Int J ClinExp Med 2015;8(8):13919-27. google scholar
20. 20. Ward MM, Hendrey MR, Malley JD, Learch TJ, Davis JC Jr, Reveille JD et al. Clinical and immunogenetic prognostic factors for radiographic severity in ankylosing spondylitis. Arthritis Rheum 2009;61(7):859-66. [CrossRef] google scholar
21. 21. Akar S, Kaplan YC, Ecemiş S, Keskin-Arslan E, Gercik Ö, Gücenmez S, et al. The role of smoking in the development and progression of structural damage in axial SpA patients: A systematic review and meta-analysis. Eur J Rheumatol 2018;6(4):184-92. [CrossRef] google scholar
22. 22. Haroon N, Inman RD, Learch TJ, Weisman MH, Lee M, Rahbar M, et al. The impact of tumor necrosis factor a inhibitors on radiographic progression in ankylosing spondylitis. Arthritis Rheum 2013;65(10):2645-54. [CrossRef] google scholar
23. 23. Fallahi S. The Correlation between Pack-Years of Smoking and Disease Activity, Quality of Life, Spinal Mobility, and Sacroiliitis Grading in Patients with Ankylosing Spondylitis. Turk J Rheumatol 2013;28(3):181-8. [CrossRef] google scholar
24. 24. Reed MD, Dharmage S, Boers A, Martin BJ, Buchanan RR, Schachna L. Ankylosing spondylitis: an Australian experience. Intern Med J 2008;38(5):321-7. [CrossRef] google scholar
25. 25. Mattey DL, Dawson SR, Healey EL, Packham JC. Relationship between smoking and patient-reported measures of disease outcome in ankylosing spondylitis. J Rheumatol 2011;38(12):2608-15. [CrossRef] google scholar
26. 26. Bodur H, Ataman S, Rezvani A, Buğdaycı DS, Cevik R, Birtane M, et al. Quality of life and related variables in patients with ankylosing spondylitis. Quality of life research: an international journal of quality of life aspects of treatment, Qual Life Res 2011;20(4):543-9. [CrossRef] google scholar
27. 27. Rudwaleit M, Listing J, Brandt J, Braun J, Sieper J. Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor alpha blockers in ankylosing spondylitis. Ann Rheum Dis 2004;63(6):665-70. [CrossRef] google scholar
28. 28. Lord PA, Farragher TM, Lunt M, Watson KD, Symmons DP, Hyrich KL, et al. Predictors of response to anti-TNF therapy in ankylosing spondylitis: results from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford) 2010;49(3):563-70. [CrossRef] google scholar
29. 29. Sieper J, Poddubnyy D, Pangan A, Rathmann S, Anderson J. Smoking was not Associated with Response to Adalimumab Therapy in Patients with Non-Radiographic Axial Spondyloarthritis. Ann Rheum Dis 2013;72:A286. [CrossRef] google scholar
30. 30. Jones GT, Ratz T, Dean LE, Macfarlane GJ, Atzeni F. Disease Severity in Never Smokers, Ex-Smokers, and Current Smokers With Axial Spondyloarthritis: Results From the Scotland Registry for Ankylosing Spondylitis. Arthritis Care Res (Hoboken) 2017;69(9):1407-13. [CrossRef] google scholar