Anti-tumor necrosis factor alpha treatment does not influence serum levels of the markers associated with radiographic progression in ankylosing spondylitis

Abstract

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.

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.

A written informed consent was obtained from each patient.

Data Sharing Statement:
The data that support the findings of this study are available from the corresponding author upon reasonable request.

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.

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

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