Skip to main content
SpringerLink
Log in

Disease Activity-Guided Stepwise Tapering but Not Discontinuation of Biologics Is a Feasible Therapeutic Strategy for Patients with Ankylosing Spondylitis: Real-World Evidence

  • Original Research
  • Published:
Advances in Therapy Aims and scope Submit manuscript

Abstract

Objectives

To analyze the history of biologics usage in patients with ankylosing spondylitis (AS) in China and to evaluate the impact of drug reduction and withdrawal on disease activity.

Methods

Drug administration intervals and disease activity indexes in patients with AS who regularly used etanercept (ETN) biosimilars for more than 1 year and those who withdrew the drugs during the same period in a single center were analyzed retrospectively.

Results

A total of 108 patients with AS who used ETN biosimilars for more than a year were recruited in this study for analysis. (1) Overall, 98.1% patients with AS increased the intervals between drug administrations, averaging from 4.57 ± 0.15 days during 0–3 months to 8.53 ± 0.43 days during 3–6 months, and to 10.49 ± 0.39 days during 6–12 months. Compared with the baseline parameters, after 3-month and 12-month treatments disease activities were improved significantly, including Patient Global Assessment (PTGA), overall back pain, nocturnal pain, fatigue, Ankylosing Spondylitis Disease Activity Score–C-Reactive Protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index (BASFI). (2) Only 59.3% used ETN biosimilars with full dose (3.5 days’ interval) in the first 3 months. At baseline, disease activities of these patients were higher than those with reduced dose (5.9 days’ interval). However, at 12 months of drug administration there was no significant difference in the overall length of drug administration intervals and disease activities between the two groups. (3) Twenty patients with low disease activity (LDA) discontinued therapy spontaneously; after 3 months, 55% of them experienced disease recurrence (∆ASDAS ≥ 0.9).

Conclusion

Spontaneous dose reduction was a common phenomenon among patients with AS in China, which becomes more notable with increasing relief of symptoms. Most patients could maintain an LDA state after dose reduction. Compared with dose reduction, ETN biosimilar withdrawal was more likely to induce disease recurrence. Therefore, disease activity-guided individualized stepwise tapering may become one of the feasible therapeutic strategies for AS in the future.

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
Fig. 3

Similar content being viewed by others

References

  1. Calin A, Dijkmans BA, Emery P, et al. Outcomes of a multicentre randomised clinical trial of etanercept to treat ankylosing spondylitis. Ann Rheum Dis. 2004;63:1594–600. https://doi.org/10.1136/ard.2004.020875.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. van den Berg R, Stanislawska-Biernat E, van der Heijde DM. Comparison of recommendations for the use of anti-tumour necrosis factor therapy in ankylosing spondylitis in 23 countries worldwide. Rheumatology (Oxford). 2011;50:2270–7. https://doi.org/10.1093/rheumatology/ker270.

    Article  Google Scholar 

  3. van der Heijde D, Ramiro S, Landewé R, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017;76:978–91. https://doi.org/10.1136/annrheumdis-2016-210770.

    Article  PubMed  Google Scholar 

  4. Ward MM, Deodhar A, Akl EA, 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. https://doi.org/10.1002/art.39298.

    Article  PubMed  Google Scholar 

  5. Ward MM, Deodhar A, Gensler LS, et al. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and treatment network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Care Res (Hoboken). 2019;71(10):1285–99.

  6. Smolen JS, Braun J, Dougados M, et al. Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force. Ann Rheum Dis. 2014;73(1):6–16. https://doi.org/10.1136/annrheumdis-2013-203419.

    Article  PubMed  Google Scholar 

  7. Calin A, Dijkmans BA, Emery P, et al. Outcomes of a multicentre randomised clinical trial of etanercept to treat ankylosing spondylitis. Ann Rheum Dis. 2004;63(12):1594–600. https://doi.org/10.1136/ard.2004.020875.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 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. https://doi.org/10.1136/ard.2009.124446.

    Article  CAS  PubMed  Google Scholar 

  9. Kristensen LE, Karlsson JA, Englund M, Petersson IF, Saxne T, Geborek P. Presence of peripheral arthritis and male sex predicting continuation of anti-tumor necrosis factor therapy in ankylosing spondylitis: an observational prospective cohort study from the South Swedish Arthritis Treatment Group Register. Arthritis Care Res (Hoboken). 2010;62:1362–9. https://doi.org/10.1002/acr.20258.

    Article  CAS  Google Scholar 

  10. Ji XJ, Wang YW, Hu ZY, Ma YP, Huang F. Effectiveness of subcutaneous tumor necrosis factor inhibitors in patients with ankylosing spondylitis: a real-world prospective observational cohort study in China. Front Pharmacol. 2019;17(10):1476. https://doi.org/10.3389/fphar.2019.01476.

    Article  CAS  Google Scholar 

  11. Navarro-Compan V, Moreira V, Ariza-Ariza R, Hernandez-Cruz B, VargasLebron C, Navarro-Sarabia F. Low doses of etanercept can be effective in ankylosing spondylitis patients who achieve remission of the disease. Clin Rheumatol. 2011;30(7):993–6. https://doi.org/10.1007/s10067-011-1722-5.

    Article  PubMed  Google Scholar 

  12. Gratacós J, Pontes C, Juanola X, et al. Non-inferiority of dose reduction versus standard dosing of TNF-inhibitors in axial spondyloarthritis. Arthritis Res Therapy. 2019. https://doi.org/10.1186/s13075-018-1772-z.

    Article  Google Scholar 

  13. Landewé RBM, van der Heijde D, Dougados M, et al. Maintenance of clinical remission in early axial spondyloarthritis following certolizumab pegol dose reduction. Ann Rheum Dis. 2020;79(7):920–8. https://doi.org/10.1136/annrheumdis-2019-216839.

    Article  CAS  PubMed  Google Scholar 

  14. Lian F, Zhou J, Wang Y, Chen D, Xu H, Liang L. Efficiency of dose reduction strategy of etanercept in patients with axial spondyloarthritis. Clin Exp Rheumatol. 2018;36(5):884–90.

    PubMed  Google Scholar 

  15. Li KP, Jin JY, Yang JS, et al. Full dose, half dose, or discontinuation of etanercept biosimilar in early axial spondyloarthritis patients: a real-world study in China. Arch Med Sci. 2019;15(3):700–5. https://doi.org/10.5114/aoms.2018.76141.

    Article  CAS  PubMed  Google Scholar 

  16. Zhang T, Zhu J, He D, et al. Disease activity guided stepwise tapering or discontinuation of rhTNFR:Fc, an etanercept biosimilar, in patients with ankylosing spondylitis: a prospective, randomized, open-label, multicentric study. Ther Adv Musculoskelet Dis. 2020;2:12. https://doi.org/10.1177/1759720X20929441.

    Article  Google Scholar 

  17. Victoria N-C, Chamaida P-R, Eugenio DM, et al. Anti-TNF discontinuation and tapering strategies in patients with axial spondyloarthritis: a systematic literature review. Rheumatology. 2016;55(7):1188–94. https://doi.org/10.1093/rheumatology/kew033.

    Article  CAS  Google Scholar 

  18. Ruyssen-Witrand A, Rousseau V, Sommet A, et al. Factors associated with 5-year drugfree remission in early onset axial spondyloarthritis patients: data from desir cohort. Ann Rheum Dis. 2020;79:19. https://doi.org/10.1136/annrheumdis-2020-eular.3222.

  19. Uhrenholt L, Schlemmer A, Hauge E-M, et al. Dosage reduction and discontinuation of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis: protocol for a pragmatic, randomised controlled trial (the biological dose optimisation (BIODOPT) trial). BMJ Open. 2019;9(7): e028517. https://doi.org/10.1136/bmjopen-2018-028517.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Michielsens CAJ, Boers N, den Broeder N, et al. Dose reduction and withdrawal strategy for TNF-inhibitors in psoriatic arthritis and axial spondyloarthritis: design of a pragmatic open-label, randomized, non-inferiority trial. Trials. 2020;21(1):90. https://doi.org/10.1186/s13063-019-4000-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Funding

The study and the journal’s Rapid Service Fee were supported by the National Natural Science Foundation of China (Grant No. 31821003), National Key Research and Development Project (Grant No. 2018AAA0100302), Shanghai Municipal Key Clinical Specialty (shslczdzk02602), and Shanghai Science and Technology Development Funds (2020-SH-XY-2).

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Authorship Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Lingying Ye, Ling Zhou, Jianye Bian, Juan Zhao, Ting Li, Xin Wu and Huji Xu. The first draft of the manuscript was written by Lingying Ye, Ling Zhou, Jianye Bian and Huji Xu. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Disclosures

Lingying Ye, Ling Zhou, Jianye Bian, Juan Zhao, Ting Li, Xin Wu and Huji Xu declare that they have no conflict of interest.

Compliance with Ethics Guidelines

The study was conducted according to the Helsinki Declaration and approved by the ethics community of Shanghai Changzheng Hospital (ID 2017SL046). All patients gave written informed consent. Participants included in our study provided consent for publication if any identifying information is included in the manuscript.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. We thank all the participants participating in our research.

Author information

Author notes

  1. Lingying Ye, Ling Zhou, and Jianye Bian contributed equally to this paper.

Authors and Affiliations

  1. Department of Rheumatology and Immunology, Changzheng Hospital, Naval Medical University, Shanghai, 200003, China

    Lingying Ye, Ling Zhou, Jianye Bian, Juan Zhao, Ting Li, Xin Wu & Huji Xu

  2. Peking-Tsinghua Center for Life Sciences, Tsinghua University, Beijing, 100084, China

    Huji Xu

  3. School of Clinical Medicine, Tsinghua University, Beijing, 100084, China

    Huji Xu

Authors
  1. Lingying Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ling Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jianye Bian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Juan Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ting Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Huji Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Huji Xu.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 34 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ye, L., Zhou, L., Bian, J. et al. Disease Activity-Guided Stepwise Tapering but Not Discontinuation of Biologics Is a Feasible Therapeutic Strategy for Patients with Ankylosing Spondylitis: Real-World Evidence. Adv Ther 39, 1393–1402 (2022). https://doi.org/10.1007/s12325-021-01995-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-021-01995-1

Keywords

Search

Navigation