Skip to main content
SpringerLink
Log in

Neuropathic pain in axial spondyloarthropathy is underdiagnosed and a confounding factor in biologic drug–switching decision: a cross-sectional study

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Objectives

The aim of this study was to evaluate the relationship between the presence of neuropathic pain (NeP), disease activity scores and biologic drug–switching decisions in the subjects with axial spondyloarthritis (axSpA) receiving biologic treatment.

Methods

PainDETECT Questionnaire was used to evaluate the presence of NeP in the patients with axSpA aged ≥18 years who had been receiving biologic treatment for at least 6 months. The relationships between disease activity scores, inflammatory markers, life quality index, biologic drug–switching decisions and the presence of NeP were analyzed.

Results

A total number of 175 patients with axSpA [ankylosing spondylitis (AS) (n:150) and non-radiographic axSpA (nr-axSpA) (n:25)] were enrolled in the study. NeP was detected in 41.7% of the patients and it was more common in females than in males (p:0.009). PainDETECT scores were positively correlated with disease activity scores, but they were not correlated with inflammatory marker levels. NeP was found to be significantly more common in whom the biologics had been switched 3 or more times (p:0.007). PainDETECT scores were higher and NeP was more prevalent (p:0.028) in the patients for whom drug-switching decisions had been made due to primary or secondary unresponsiveness.

Conclusion

NeP is more common than estimated in the patients with axSpA and current disease activity scores are insufficient to make a distinction between NeP and inflammatory pain. NeP is a confounding factor in the evaluation of treatment response to biologic agents. In the subjects with AS and nr-axSpA with primary or secondary treatment unresponsiveness, the presence of NeP must be considered before biologic drug–switching decisions.

Key Points

• Neuropathic pain (NeP) is common in subjects with AxSpA treated with multiple biologic agents.

• Current disease activity scores for AxSpA are insufficient to make a differentiation between NeP and inflammatory pain.

• NeP is a confounding factor in the evaluation of treatment response to biologic agents.

• Patients with AxSpA should be re-evaluated in terms of the presence of neuropathic pain before making biologic drug-switching decisions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Sieper J, Braun J, Dougados M, Baeten D (2015) Axial spondyloarthritis. Nat Rev Dis Primers 1:15013. https://doi.org/10.1038/nrdp.2015.13

    Article  PubMed  Google Scholar 

  2. Gok K, Cengiz G, Erol K, Ozgocmen S (2018) Neuropathic pain component in axial spondyloarthritis and the ınfluence on disease burden. J Clin Rheumatol 24(6):324–327. https://doi.org/10.1097/RHU.0000000000000711

    Article  PubMed  Google Scholar 

  3. Kim TW, Son SM, Lee JS (2020) Neuropathic pain in ankylosing spondylitis: a meta-analysis. Neuropathischer Schmerz bei ankylosierender Spondylitis – eine Metaanalyse. Z Rheumatol 79(1):95–102. https://doi.org/10.1007/s00393-019-0654-3

    Article  CAS  PubMed  Google Scholar 

  4. Wu Q, Inman RD, Davis KD (2013) Neuropathic pain in ankylosing spondylitis: a psychophysics and brain imaging study. Arthritis Rheum 65(6):1494–1503. https://doi.org/10.1002/art.37920

    Article  PubMed  Google Scholar 

  5. Mease PJ (2017) Fibromyalgia, a missed comorbidity in spondyloarthritis: prevalence and impact on assessment and treatment. Curr Opin Rheumatol 29(4):304–310. https://doi.org/10.1097/BOR.0000000000000388

    Article  PubMed  Google Scholar 

  6. Macfarlane GJ et al (2017) Co-occurrence and characteristics of patients with axial spondyloarthritis who meet criteria for fibromyalgia: results from a UK National Register. Arthritis Rheumatol 69(11):2144–2150. https://doi.org/10.1002/art.40185

    Article  PubMed  Google Scholar 

  7. Gau SY, Lee YH, Tsou HK, Huang JY, Chen X, Ye Z, Wei JC (2021) Patients with ankylosing spondylitis are associated with high risk of fibromyalgia: a nationwide population-based cohort study. Front Med (Lausanne) 8:618594. https://doi.org/10.3389/fmed.2021.618594

    Article  PubMed  Google Scholar 

  8. Freynhagen R, Baron R, Gockel U, Tölle TR (2006) painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin 22(10):1911–1920. https://doi.org/10.1185/030079906X132488

    Article  PubMed  Google Scholar 

  9. Rudwaleit M, van der Heijde D, Landewé R et al (2009) The development of assessment of spondyloarthritis international society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 68(6):777–783. https://doi.org/10.1136/ard.2009.108233

    Article  CAS  PubMed  Google Scholar 

  10. Braun J, Sieper J (2007) Ankylosing spondylitis. Lancet 369(9570):1379–1390. https://doi.org/10.1016/S0140-6736(07)60635-7

    Article  PubMed  Google Scholar 

  11. McCormack HM, Horne DJ, Sheather S (1988) Clinical applications of visual analogue scales: a critical review. Psychol Med 18(4):1007–1019. https://doi.org/10.1017/s0033291700009934

    Article  CAS  PubMed  Google Scholar 

  12. Alkan H et al (2013) Turkish version of the painDETECT questionnaire in the assessment of neuropathic pain: a validity and reliability study. Pain med (Malden, Mass.) 14(12):1933–1943. https://doi.org/10.1111/pme.12222

    Article  Google Scholar 

  13. Garrett S et al (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 

  14. Haywood KL, Garratt AM, Dawes PT (2005) Patient-assessed health in ankylosing spondylitis: a structured review. Rheumatology (Oxford) 44(5):577–586. https://doi.org/10.1093/rheumatology/keh549

    Article  CAS  PubMed  Google Scholar 

  15. Wolfe F et al (2010) The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken) 62(5):600–610. https://doi.org/10.1002/acr.20140

    Article  PubMed  Google Scholar 

  16. Choi JH, Lee SH, Kim HR, Lee KA (2018) Association of neuropathic-like pain characteristics with clinical and radiographic features in patients with ankylosing spondylitis. Clin Rheumatol 37(11):3077–3086. https://doi.org/10.1007/s10067-018-4125-z

    Article  PubMed  Google Scholar 

  17. Atar E, Askin A (2020) Somatosensory dysfunction related neuropathic pain component affects disease activity, functional status and quality of life in ankylosing spondylitis. Int J Rheum Dis 23(12):1656–1663. https://doi.org/10.1111/1756-185X.13993

    Article  CAS  PubMed  Google Scholar 

  18. Geler-Külcü D, Batıbay S, Öztürk G, Mesci N (2018) The association of neuropathic pain and disease activity, functional level, and quality of life in patients with ankylosing spondylitis: a cross-sectional study. Turk J Med Sci 48(2):257–265. https://doi.org/10.3906/sag-1707-147

    Article  PubMed  Google Scholar 

  19. Koca T, Göğebakan H, Çetin G (2019) Should central sensitization and neuropathic pain be considered in disease activity and treatment decision in axial ankylosing spondilitis? Cukurova Med J 44(4):1–10. https://doi.org/10.17826/cumj.503652

    Article  Google Scholar 

  20. Garip Y, Eser F, Kılıçarslan A, Bodur H (2015) Prevalence of neuropathic pain in rheumatic disorders: association with disease activity, functional status and quality of life. Arch Rheumatol 30(3):231–237. https://doi.org/10.5606/ArchRheumatol.2015.5295

    Article  Google Scholar 

  21. Bidad K, Gracey E, Hemington KS, Mapplebeck JCS, Davis KD, Inman RD (2017) Pain in ankylosing spondylitis: a neuro-immune collaboration. Nat Rev Rheumatol 13(7):410–420. https://doi.org/10.1038/nrrheum.2017.92

    Article  CAS  PubMed  Google Scholar 

  22. Sieper J, Poddubnyy D (2017) Axial spondyloarthritis. Lancet 390(10089):73–84. https://doi.org/10.1016/S0140-6736(16)31591-4

    Article  PubMed  Google Scholar 

  23. Hess A et al (2011) Blockade of TNF-α rapidly inhibits pain responses in the central nervous system. Proc Natl Acad Sci U S A 108(9):3731–3736. https://doi.org/10.1073/pnas.1011774108

    Article  PubMed  PubMed Central  Google Scholar 

  24. Danve A, Deodhar A (2017) Treat to target in axial spondyloarthritis: what are the ıssues? Curr Rheumatol Rep 19(5):22. https://doi.org/10.1007/s11926-017-0648-6

    Article  PubMed  Google Scholar 

  25. Ramiro S (2022) Update of the ASAS/EULAR recommendations on the management of axial spondyloarthritis. In: Oral presentation in the EULAR recommendations session. EULAR Congress, Copenhagen, Denmark

    Google Scholar 

  26. Son SM, Kim DS, Lee JS (2022) Fibromyalgia in axial spondyloarthritis: a meta-analysis. J Clin Rheumatol 28(1):e222–e227. https://doi.org/10.1097/RHU.0000000000001612

    Article  PubMed  Google Scholar 

  27. van der Horst-Bruinsma IE, Zack DJ, Szumski A, Koenig AS (2013) Female patients with ankylosing spondylitis: analysis of the impact of gender across treatment studies. Ann Rheum Dis 72(7):1221–1224. https://doi.org/10.1136/annrheumdis-2012-202431

    Article  PubMed  Google Scholar 

  28. Lee W et al (2007) Are there gender differences in severity of ankylosing spondylitis? Results from the PSOAS cohort. Ann Rheum Dis 66(5):633–638. https://doi.org/10.1136/ard.2006.060293

    Article  PubMed  Google Scholar 

  29. Ji Y, He Y, Nian X, Sun E, Li L (2019) Inflammatory or neuropathic pain: characteristics and their relationships with disease activity and functional status in axial spondyloarthritis patients. Pain Med 20(5):882–888. https://doi.org/10.1093/pm/pny138

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Akdeniz University School of Medicine, Antalya, Turkey

    Tahir S. Öğüt, Funda Erbasan, Mustafa E. Terzioğlu, Bengisu Aslan & Veli Yazisiz

  2. Allergy and Clinical Immunology, Sultan 1, Murat State Hospital, Edirne, Turkey

    Ece Çelik

Authors
  1. Tahir S. Öğüt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Funda Erbasan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mustafa E. Terzioğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bengisu Aslan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ece Çelik
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Veli Yazisiz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Veli Yazisiz.

Ethics declarations

Disclosures

None

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Öğüt, T.S., Erbasan, F., Terzioğlu, M.E. et al. Neuropathic pain in axial spondyloarthropathy is underdiagnosed and a confounding factor in biologic drug–switching decision: a cross-sectional study. Clin Rheumatol 42, 1275–1284 (2023). https://doi.org/10.1007/s10067-023-06531-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-023-06531-w

Keywords

Search

Navigation