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Influence of smoking and obesity on treatment response in patients with axial spondyloarthritis: a systematic literature review


To assess whether smoking and obesity are predictors of poor treatment response in patients with axial spondyloarthritis (axSpA). A systematic literature review was performed by searching in MEDLINE and EMBASE up to June 2019 with a strategy based on the PICO approach: Population: patients with axSpA; Intervention or exposure: smoking or obesity; Comparison: non-smokers (for smoking) and normal-weight individuals (for obesity); and Outcome: any response criteria currently validated for axSpA. The 2009 Oxford Centre for Evidence-based Medicine levels were used for assessing the studies quality. Out of 1873 references retrieved, 46 studies were selected for full-text review and 12 for data extraction: six stratified patients by smoking and six by obesity. All were longitudinal observational studies, except one, which was cross-sectional. Overall, these studies included 5291 patients (3917 for smoking and 1333 for obesity), and all these patients were on anti-tumor necrosis factor (anti-TNF) therapy. The quality of evidence was graded as level 2b except that from the cross-sectional study which was graded level 4. For smoking, the evidence found is inconsistent: two studies finding negative effects in response to anti-TNF while the other four found no differences in clinical response to this therapy. Regarding obesity, the evidence is more consistent: five of the six studies describing a negative influence in response to anti-TNF. According to the scientific evidence in patients with axSpA, obesity is associated with a more unsatisfactory response to anti-TNF therapy. A poorer response in smokers has yet to be demonstrated.

Key Points
• Identifying predictors of treatment response in axSpA, especially those that are modifiable, is relevant.
• Obesity increases the risk of poorer response to anti-TNF agents in patients with axSpA.
• Scientific evidence for smoking habit as a predictor of treatment response in axSpA is inconclusive.

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  1. Navarro-Compan V, Plasencia-Rodriguez C, de Miguel E, Diaz Del Campo P, Balsa A, Gratacos J (2017) Switching biological disease-modifying antirheumatic drugs in patients with axial spondyloarthritis: results from a systematic literature review. RMD Open 3(2):e000524

    Article  Google Scholar 

  2. Glintborg B, Ostergaard M, Krogh NS, Dreyer L, Kristensen HL, Hetland ML (2010) Predictors of treatment response and drug continuation in 842 patients with ankylosing spondylitis treated with anti-tumour necrosis factor: results from 8 years’ surveillance in the Danish nationwide DANBIO registry. Ann Rheum Dis 69(11):2002–2008

    CAS  Article  Google Scholar 

  3. Maneiro JR, Souto A, Salgado E, Mera A, Gomez-Reino JJ (2015) Predictors of response to TNF antagonists in patients with ankylosing spondylitis and psoriatic arthritis: systematic review and meta-analysis. RMD Open 1(1):e000017

    Article  Google Scholar 

  4. Villaverde-Garcia V, Cobo-Ibáñez T, Seoane-Mato D, Díaz Del Campo-Fontecha P, Guerra M, Candelas-Rodríguez G et al (2016) The effect of smoking on clinical and structural damage in patients with ankylosing spondylitis and axial spondyloarthritis: a systematic literature review. Ann Rheum Dis 75:339

    Article  Google Scholar 

  5. Maas F, Arends S, Van Der Veer E, Wink F, Efde M, Bootsma H et al (2016) Obesity is common in axial spondyloarthritis and is associated with poor clinical outcome. J Rheumatol 43(2):383–387

    CAS  Article  Google Scholar 

  6. van der Heijde D, Ramiro S, Landewe R, Baraliakos X, Van den Bosch F, Sepriano A et al (2017) 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis 76(6):978–991

    Article  Google Scholar 

  7. Ottaviani S, Allanore Y, Tubach F, Forien M, Gardette A, Pasquet B, Palazzo E, Meunier M, Hayem G, Job-Deslandre C, Kahan A, Meyer O, Dieudé P (2012) Body mass index influences the response to infliximab in ankylosing spondylitis. Arthritis Res Ther 14(3):R115

    CAS  Article  Google Scholar 

  8. Gremese E, Bernardi S, Bonazza S, Nowik M, Peluso G, Massara A, Tolusso B, Messuti L, Miceli MC, Zoli A, Trotta F, Govoni M, Ferraccioli G (2014) Body weight, gender and response to TNF-α blockers in axial spondyloarthritis. Rheumatology (United Kingdom) 53(5):875–881

    CAS  Article  Google Scholar 

  9. Micheroli R, Hebeisen M, Wildi LM, Exer P, Tamborrini G, Bernhard J et al (2017) Impact of obesity on the response to tumor necrosis factor inhibitors in axial spondyloarthritis. Arthritis Res Ther 19(1):164

    Article  Google Scholar 

  10. Rosas J, Llinares-Tello F, Senabre-Gallego JM, Barber-Valles X, Santos-Soler G, Salas-Heredia E et al (2017) Obesity decreases clinical efficacy and levels of adalimumab in patients with ankylosing spondylitis. Clin Exp Rheumatol 35(1):145–148

    PubMed  Google Scholar 

  11. Hernández-Breijo B, Plasencia-Rodríguez C, Navarro-Compán V, Martínez-Feito A, Jochems A, Kneepkens EL, et al. (2019) Association between concomitant csDMARDs and clinical response to TNF inhibitors in overweight patients with axial spondyloarthritis. Arthritis Res Ther

  12. Hernandez MV, Sanchez-Piedra C, Garcia-Magallon B, Cuende E, Manero J, Campos-Fernandez C et al (2019) Factors associated with long-term retention of treatment with golimumab in a real-world setting: an analysis of the Spanish BIOBADASER registry. Rheumatol Int 39(3):509–515

    CAS  Article  Google Scholar 

  13. Glintborg B, Højgaard P, Lund Hetland M, Steen Krogh N, Kollerup G, Jensen J, Chrysidis S, Jensen Hansen IM, Holland-Fischer M, Højland Hansen T, Nilsson C, Espesen J, Nordin H, Rasmussen Loft AG, Pelck R, Lorenzen T, Flejsborg Oeftiger S, Unger B, Jaeger F, Mosborg Petersen P, Rasmussen C, Dreyer L (2016) Impact of tobacco smoking on response to tumour necrosis factor-alpha inhibitor treatment in patients with ankylosing spondylitis: results from the Danish nationwide DANBIO registry. Rheumatology (United Kingdom) 55(4):659–668

    CAS  Article  Google Scholar 

  14. Ciurea A, Scherer A, Weber U, Exer P, Bernhard J, Tamborrini G, Riek M, Müller RB, Weiss B, Nissen MJ, Kissling R, Michel BA, Finckh A, Rheumatologists of Swiss Clinical Quality Management Program for Axial Spondyloarthritis (2016) Impaired response to treatment with tumour necrosis factor α inhibitors in smokers with axial spondyloarthritis. Ann Rheum Dis 75(3):532–539

    CAS  Article  Google Scholar 

  15. Kydd AS, Chen JS, Makovey J, Chand V, Henderson L, Buchbinder R et al (2015) Smoking did not modify the effects of anti-TNF treatment on health-related quality of life among Australian ankylosing spondylitis patients. Rheumatology (Oxford) 54(2):310–317

    CAS  Article  Google Scholar 

  16. Zhao S, Yoshida K, Jones GT, Hughes DM, Tedeschi SK, Lyu H et al (2019) The impact of smoking on response to TNF inhibitors in axial spondyloarthritis: methodological considerations for longitudinal observational studies. Arthritis Care Res (Hoboken)

  17. Zhao SS, Yoshida K, Jones GT, Hughes DM, Duffield SJ, Tedeschi SK, Lyu H, Moots RJ, Solomon DH, Goodson NJ (2019) Smoking status and cause-specific discontinuation of tumour necrosis factor inhibitors in axial spondyloarthritis. Arthritis Res Ther 21(1):177

    Article  Google Scholar 

  18. Saad CGS, Abreu AS, Ribeiro ACM, Moraes JCB, Perandini LA, Dassouki T et al (2013) Fat mass and resistin: predictive factors for anti-TNF therapy response in ankylosing spondylitis patients. Arthritis Rheum 65:S1058

    Google Scholar 

  19. Ibanez Vodnizza SE, Nurmohamed MT, Visman IM, van Denderen JC, Lems WF, Jaime F et al (2017) Fat mass lowers the response to tumor necrosis factor-alpha blockers in patients with ankylosing spondylitis. J Rheumatol 44(9):1355–1361

    Article  Google Scholar 

  20. Singh S, Facciorusso A, Singh AG, VandeCasteele N, Zarrinpar A, Grunvald E et al (2017) Obesity is associated with inferior response to anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review and meta-analysis. Gastroenterology 152(5):S154

    Article  Google Scholar 

  21. Shan J, Zhang J (2019) Impact of obesity on the efficacy of different biologic agents in inflammatory diseases: a systematic review and meta-analysis. Joint Bone Spine 86(2):173–183

    CAS  Article  Google Scholar 

  22. Lord PA, Farragher TM, Lunt M, Watson KD, Symmons DP, Hyrich KL (2010) Predictors of response to anti-TNF therapy in ankylosing spondylitis: results from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford) 49(3):563–570

    CAS  Article  Google Scholar 

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The authors would like to thank the Spanish Society of Rheumatology for editing the manuscript.

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Correspondence to Pablo Antonio Zurita Prada.

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PZP: Consultancy or grants from Roche, Pfizer, Lylly, and Novartis outside the submitted work

CUL: Grants from Pfizer, Lylly, and Novartis

CGA: Speaker for Janssen, Novartis, Roche, Pfizer, Abbvie, Menarini, Gebro, and GrünenthalScientific consulting for Janssen, Novartis, Gebro, and Grünenthal. Research grants and funding from Janssen, Novartis, and Pfizer

SKC: No conflict of interest

VNC: Grants or personal fees from Abbvie, Lilly, MSD, Novartis, Pfizer, UCM outside the submitted work

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Zurita Prada, P.A., Urrego Laurín, C.L., Guillén Astete, C.A. et al. Influence of smoking and obesity on treatment response in patients with axial spondyloarthritis: a systematic literature review. Clin Rheumatol 40, 1673–1686 (2021).

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  • Ankylosing spondylitis
  • Axial spondyloarthritis
  • Body mass index
  • Clinical response
  • Efficacy
  • Obesity
  • Outcome
  • Overweight
  • Predictors
  • Tobacco