Ali Erhan Özdemirel1, Serdar Can Güven2, Alper Doğancı3, Zühre Sarı Sürmeli4, Ayla Özyuvalı5, Mehmet Kurt6, Diana Rüstemova7, Selin Hassan8, Ayşe Peyman Yalçın Sayın9, Hüseyin Tutkak10, Şebnem Ataman9

1Department of Rheumatology, Liv Hospital, Ankara, Türkiye
2Department of Rheumatology, Ankara City Hospital, Ankara, Türkiye
3Department of Physical and Rehabilitation Medicine, Erzurum Regional Training and Research Hospital, Erzurum, Türkiye
4Department of Rheumatology, Aydın State Hospital, Aydın, Türkiye
5Department of Physical and Rehabilitation Medicine, HFM Beyazpınar Physical Medicine And Rehabilitation Centre, Ankara, Türkiye
6Department of Physical and Rehabilitation Medicine, Dr. Ergun Özdemir Görele State Hospital, Giresun, Türkiye
7Department of Physical and Rehabilitation Medicine, Can Private Hospital, Manisa, Türkiye
8Department of Physical and Rehabilitation Medicine, Başkent University Medical School, Ankara, Türkiye
9Department of Rheumatology, Ankara University Medical School, Ankara, Türkiye
10Department of Immunology and Allergy, Ankara University Medical School, Ankara, Türkiye

Keywords: Ankylosing spondylitis, bone morphogenetic protein, Dickkopf-1, sclerostin.


Objectives: The study aimed to determine the levels of change of the markers related to radiographic progression, such as Dickkopf-1 (DKK-1), sclerostin (SOST), bone morphogenetic protein (BMP)-2 and -4, and interleukin (IL)-17 and -23, in ankylosing spondyloarthritis (AS) during anti-tumor necrosis factor alpha (TNF-α) treatment.

Patients and methods: Fifty-three anti-TNF-α naïve AS patients (34 males, 19 females; median: 38 years; range, 20 to 52 years) refractory to conventional treatments meeting the modified New York criteria or Assessment of SpondyloArthritis International Society classification criteria were enrolled to this cross-sectional, controlled study between October 2015 and January 2017. Fifty healthy volunteers (35 males, 15 females; median: 36 years; range, 18 to 55 years) with similar age and sex characteristics were recruited. Serum DKK-1, BMP-2, BMP-4, SOST, IL-17, and IL-23 levels were measured in both groups. The serum levels of the markers were measured again after about two years (mean follow-up duration of 21.7±6.4 months) in AS patients who started anti-TNF-α treatment. Demographic, clinical characteristics, and laboratory parameters were recorded. The disease activity at the time of inclusion was assessed through the Bath Ankylosing Spondylitis Disease Activity Index.

Results: Serum DKK-1, SOST, IL-17, and IL-23 levels in the AS group before anti-TNF-a treatment were significantly higher compared to the control group (p<0.01 for DKK-1, p<0.001 for others). There was no difference regarding serum BMP-4 levels, whereas BMP-2 levels were significantly higher in the control group (p<0.01). Forty (75.47%) AS patients had serum marker levels measured after anti-TNF-α treatment. No significant change was observed in the serum levels of these 40 patients measured 21.7±6.4 months after the initiation of anti-TNF-α treatment (p>0.05 for all).

Conclusion: In AS patients, there was no change in DKK-1/SOST, BMP, and IL-17/23 cascade with anti-TNF-α treatment. This finding may suggest that these pathways act independently of each other, and their local effects are not influenced by systemic inflammation.

Citation: Özdemirel AE, Güven SC, Doğancı A, Sarı Sürmeli Z, Özyuvalı A, Kurt M, et al. Anti-tumor necrosis factor alphatreatment does not influence serum levels of the markers associated with radiographic progression in ankylosing spondylitis. Arch Rheumatol 2023;38(1):148-155.

Ethics Committee Approval

The study protocol was approved by the Ankara University Medical School Ethics Committee (date: 11.03.2013, IRB: 04-160-13, 11.03.2013). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Author Contributions

Concept and design: Özdemirel AE, Tutkak H, Yalçın Sayın AP, Ataman . Supervision: Tutkak H, Yalçın Sayın AP, Ataman , Data collection: Özdemirel AE, Do¤ancı A, Sarı Sürmeli Z, Özyuvalı A, Kurt M, Rüstemova D, Hassan S, Data analysis: Özdemirel AE, Güven SC. Interpretation of the data: Özdemirel AE, Güven SC. Writing the manuscript: Özdemirel AE, Güven SC. All authors approved the final version of the manuscript.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

This research received bursary from Ankara University The Scientific Research Projects Coordination Unit.