Skip to main content
SpringerLink
Log in

Clinical Features and Drug Retention of TNF Inhibitors in Older Patients with Ankylosing Spondylitis: Results from the KOBIO Registry

  • Original Research Article
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

Objectives

This study aimed to analyse the clinical features and outcomes of and reasons for discontinuing tumour necrosis factor (TNF) inhibitor therapy in older patients with ankylosing spondylitis (AS).

Methods

Data were extracted from the nationwide Korean College of Rheumatology Biologics registry. Clinical variables and outcomes were compared, and drug retention rate was evaluated.

Results

Among 1524 patients with AS treated with TNF inhibitors, 306 were aged ≥ 50 years (‘older patients’). Fewer patients were male, the incidence of hypertension and diabetes was higher (all p < 0.001), and the proportion of peripheral arthritis (35.6 vs. 27.1%), Ankylosing Spondylitis Disease Activity Score‒erythrocyte sedimentation rate (4.0 ± 1.1 vs. 3.6 ± 1.0), and Bath Ankylosing Spondylitis Functional Index (4.2 ± 2.6 vs. 3.3 ± 2.5) were all higher in older patients. Although the drug retention rate was lower (log-rank p = 0.018) and lack of efficacy and adverse events were more frequent in older patients (both p < 0.001), drug retention rates were not different after propensity score matching (log-rank p = 0.23). Improvements in disease activity and manifestations were comparable between groups, except for the incidence of peripheral arthritis, which decreased significantly less in older patients over 3 and 5 years.

Conclusion

Improvements in disease-related clinical factors and drug retention rates were not different between older and younger patients with AS receiving TNF inhibitors. However, the incidence of adverse events was higher in older patients.

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. Braun J, Sieper J. Ankylosing spondylitis. Lancet. 2007;369:1379–90.

    Article  Google Scholar 

  2. Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet. 2017;390:73–84.

    Article  Google Scholar 

  3. Dean LE, Jones GT, MacDonald AG, Downham C, Sturrock RD, Macfarlane GJ. Global prevalence of ankylosing spondylitis. Rheumatology. 2014;53:650–7.

    Article  Google Scholar 

  4. Van Tubergen A. The changing clinical picture and epidemiology of spondyloarthritis. Nat Rev Rheumatol. 2015;11:110.

    Article  Google Scholar 

  5. Ward MM, Learch TJ, Gensler LS, Davis JC Jr, Reveille JD, Weisman MH. Regional radiographic damage and functional limitations in patients with ankylosing spondylitis: differences in early and late disease. Arthritis Care Res (Hoboken). 2013;65:257–65.

    Article  Google Scholar 

  6. Exarchou S, Lie E, Lindström U, Askling J, Forsblad-d’Elia H, Turesson C, et al. Mortality in ankylosing spondylitis: results from a nationwide population-based study. Ann Rheum Dis. 2016;75:1466–72.

    Article  Google Scholar 

  7. Taurog JD, Chhabra A, Colbert RA. Ankylosing spondylitis and axial spondyloarthritis. N Engl J Med. 2016;374:2563–74.

    Article  Google Scholar 

  8. Carbo MJ, Spoorenberg A, Maas F, Brouwer E, Bos R, Bootsma H, et al. Ankylosing spondylitis disease activity score is related to NSAID use, especially in patients treated with TNF-α inhibitors. PLoS One. 2018;13:e0196281.

    Article  Google Scholar 

  9. Poddubnyy D, Rudwaleit M. Adalimumab for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis–a five-year update. Expert Opin Biol Ther. 2013;13:1599–611.

    Article  CAS  Google Scholar 

  10. Davis JC, van der Heijde DM, Braun J, Dougados M, Clegg DO, Kivitz AJ, et al. Efficacy and safety of up to 192 weeks of etanercept therapy in patients with ankylosing spondylitis. Ann Rheum Dis. 2008;67:346–52.

    Article  CAS  Google Scholar 

  11. Braun J, Baraliakos X, Listing J, Fritz C, Alten R, Burmester G, et al. Persistent clinical efficacy and safety of anti-tumour necrosis factor α therapy with infliximab in patients with ankylosing spondylitis over 5 years: evidence for different types of response. Ann Rheum Dis. 2008;67:340–5.

    Article  CAS  Google Scholar 

  12. Braun J, Pham T, Sieper J, Davis J, Van der Linden S, Dougados M, et al. International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis. Ann Rheum Dis. 2003;62:817–24.

    Article  CAS  Google Scholar 

  13. Wroński J, Fiedor P. The safety profile of tumor necrosis factor inhibitors in ankylosing spondylitis: are TNF inhibitors safer than we thought? J Clin Pharm. 2019;59:445–62.

    Article  Google Scholar 

  14. Plasencia C, Kneepkens EL, Wolbink G, Krieckaert CL, Turk S, Navarro-Compán V, et al. Comparing tapering strategy to standard dosing regimen of tumor necrosis factor inhibitors in patients with spondyloarthritis in low disease activity. J Rheumatol. 2015;42:1638–46.

    Article  CAS  Google Scholar 

  15. Minozzi S, Bonovas S, Lytras T, Pecoraro V, González-Lorenzo M, Bastiampillai AJ, et al. Risk of infections using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis. Expert Opin Drug Saf. 2016;15:11–34.

    Article  CAS  Google Scholar 

  16. Maas F, Spoorenberg A, Brouwer E, Bos R, Efde M, Chaudhry RN, et al. Spinal radiographic progression in patients with ankylosing spondylitis treated with TNF-α blocking therapy: a prospective longitudinal observational cohort study. PLoS One. 2015;10:e0122693.

    Article  Google Scholar 

  17. Montilla C, Del Pino-Montes J, Collantes-Estevez E, Font P, Zarco P, Mulero J, et al. Clinical features of late-onset ankylosing spondylitis: comparison with early-onset disease. J Rheumatol. 2012;39:1008–12.

    Article  Google Scholar 

  18. Jung SM, Kwok S-K, Ju JH, Lee S-W, Song JJ, Yoon C-H, et al. Risk factors associated with inadequate control of disease activity in elderly patients with rheumatoid arthritis: results from a nationwide KOrean College of Rheumatology BIOlogics (KOBIO) registry. PLoS One. 2018;13:e0205651.

    Article  Google Scholar 

  19. Kim J, Koh JH, Choi SJ, Jeon CH, Kwok SK, Kim SK, et al. KOBIO, the first web-based Korean biologics registry operated with a unified platform among distinct disease entities. J Rheum Dis. 2021;28:176–82.

    Article  Google Scholar 

  20. Linden SVD, 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.

    Article  Google Scholar 

  21. Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol. 1994;21:2286–91.

    CAS  PubMed  Google Scholar 

  22. Lukas C, Landewé R, Sieper J, Dougados M, Davis J, Braun J, et al. Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis. 2009;68:18–24.

    Article  CAS  Google Scholar 

  23. Calin A, Garrett S, Whitelock H, Kennedy LG, O’hea J, Mallorie P, et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol. 1994;21:2281–5.

    CAS  PubMed  Google Scholar 

  24. Calin A, Elswood J, Edmunds L. Late onset ankylosing spondylitis–a distinct disorder? Br J Rheumatol. 1991;30:69–70.

    Article  CAS  Google Scholar 

  25. Derakhshan MH, Goodson NJ, Packham JC, Sengupta R, Molto A, Marzo-Ortega H, et al. Increased risk of hypertension associated with spondyloarthritis disease duration: results from the ASAS-COMOSPA study. J Rheumatol. 2019;46:701–9.

    Article  Google Scholar 

  26. Haroon NN, Paterson JM, Li P, Inman RD, Haroon N. Patients with ankylosing spondylitis have increased cardiovascular and cerebrovascular mortality: a population-based study. Ann Intern Med. 2015;163:409–16.

    Article  Google Scholar 

  27. Siao WZ, Liu CH, Wang YH, Wei JC, Jong GP. Increased risk of valvular heart disease in patients with ankylosing spondylitis: a nationwide population-based longitudinal cohort study. Adv Musculoskelet Dis. 2021;13:1759720x211021676.

  28. Kang JH, Park DJ, Lee JW, Lee KE, Wen L, Kim TJ, et al. Drug survival rates of tumor necrosis factor inhibitors in patients with rheumatoid arthritis and ankylosing spondylitis. J Korean Med Sci. 2014;29:1205–11.

    Article  CAS  Google Scholar 

  29. Gulfe A, Kapetanovic MC, Kristensen LE. Efficacy and drug survival of anti-tumour necrosis factor-alpha therapies in patients with non-radiographic axial spondyloarthritis: an observational cohort study from Southern Sweden. Scand J Rheumatol. 2014;43:493–7.

    Article  CAS  Google Scholar 

  30. Glintborg B, Ostergaard M, Krogh NS, Dreyer L, Kristensen HL, Hetland ML. 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. 2010;69:2002–8.

    Article  CAS  Google Scholar 

  31. Luc M, Gossec L, Ruyssen-Witrand A, Salliot C, Duclos M, Guignard S, et al. C-reactive protein predicts tumor necrosis factor-alpha blocker retention rate in axial ankylosing spondylitis. J Rheumatol. 2007;34:2078–81.

    CAS  PubMed  Google Scholar 

  32. Favalli EG, Selmi C, Becciolini A, Biggioggero M, Ariani A, Santilli D, et al. Eight-year retention rate of first-line tumor necrosis factor inhibitors in spondyloarthritis: a multicenter retrospective analysis. Arthritis Care Res (Hoboken). 2017;69:867–74.

    Article  CAS  Google Scholar 

  33. Kim HA, Lee SK, Oh S, Park EH, Park YB, Shin K. Comparison of retention rates between tumor necrosis factor-α inhibitors in patients with ankylosing spondylitis: data from the Korean College of Rheumatology Biologics Registry. Front Med. 2021;8:689609.

    Article  Google Scholar 

  34. Griffiths H, Smith T, Mack C, Leadbetter J, Butcher B, Acar M, et al. Persistence to biologic therapy among patients with ankylosing spondylitis: an observational study using the OPAL dataset. J Rheumatol. 2022;49:150–6.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank the KOBIO study team for their assistance with data management and preparation.

Author information

Authors and Affiliations

  1. Department of Rheumatology, Ajou University School of Medicine, Suwon, Korea

    Ji-Won Kim, Hyoun-Ah Kim, Chang-Hee Suh & Ju-Yang Jung

  2. Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea

    Eunyoung A. Lee

Authors
  1. Ji-Won Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eunyoung A. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hyoun-Ah Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chang-Hee Suh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ju-Yang Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ju-Yang Jung.

Ethics declarations

Funding

This work was supported by the new faculty research fund of Ajou University School of Medicine and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (Grant number: HI16C0992).

Conflict of interest

Ji-Won Kim, Eunyoung A Lee, Hyoun-Ah Kim, Chang-Hee Suh and Ju-Yang Jung have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

This research complied with the Helsinki Declaration. Informed consent was obtained from all enrolled participants. The same informed consent form and study protocol were provided to the independent institutional review boards/ethics committees (IRB/EC) at each medical centre, and each IRB/EC reviewed the appropriateness of the protocol, risks, and benefits to the study participants. Ultimately, the IRB/EC independently approved this study without revision of the informed consent form or study protocol.

Consent to participate

All study participants provided informed consent.

Consent for publication

Not applicable.

Availability of data and material

Data cannot be shared publicly because the Korean College of Rheumatology owns the data. Data are available from the Clinical Research Committee of KOBIO registry under the Korean College of Rheumatology for researchers who meet the criteria for access to confidential data. To request data, please contact Kichul Shin, MD, PhD Director, Korean College of Rheumatology Biologics Registry Associate Professor, Division of Rheumatology Director of Logistics Planning SMG-SNU Boramae Medical Center 20 Boramae-ro-5-gil, Dongjak-gu Seoul, 07061, Korea Tel 822 870 3204 Fax 822 870 3866, Email kideb1@snu.ac.kr

Code availability

Not applicable.

Author contributions

JWK contributed to the study design and assessment plan, manuscript conceptualization and development, and critically revised the manuscript. EL contributed to method development and testing and the data analysis and interpretation. HAK and CHS contributed to the study design and assessment plan and to manuscript development. JYJ contributed to the study design and assessment plan; data acquisition, analysis, and interpretation; and manuscript conceptualization, development, and writing. All authors read and approved the final manuscript.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 385 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, JW., Lee, E.A., Kim, HA. et al. Clinical Features and Drug Retention of TNF Inhibitors in Older Patients with Ankylosing Spondylitis: Results from the KOBIO Registry. BioDrugs 36, 411–419 (2022). https://doi.org/10.1007/s40259-022-00524-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40259-022-00524-y

Search

Navigation