Evidence of Serological IL-23/IL-17 Axis Activation in Ankylosing Spondylitis Patients with Long-Term TNF Blockade: The Missing Therapy Target?

Fernanda M. Milanez¹, Carla G.S. Saad¹, Vilma S. T. Viana¹, Julio C. B. Moraes¹, Grégory V. Périco², Celio R. Gonçalves¹ and Eloisa Bonfá¹, ¹Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, ²Unidade Radiologica Criciuma, Criciuma, Brazil

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Ankylosing spondylitis (AS), anti-TNF therapy and cytokines, IL-23

Session Information

Date: Tuesday, November 10, 2015

Title: Spondylarthropathies and Psoriatic Arthritis - Clinical Aspects and Treatment Poster III: Therapy

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Spondyloarthritis (Spa) is a group of inflammatory diseases in which ankylosing spondylitis (AS) is the prototype. Despite recent advances in pathophysiology and treatment, this group is still a challenge, particularly regarding the understanding of the inflammatory pathways involved, predictors of anti-TNF response and risk factors for radiographic progression. The aim of our study was to investigate the long-term influence of TNF-blockage in IL-23/IL-17 axis of ankylosing spondylitis (AS) patients.

Methods: Eighty-six AS anti-TNF naïve patients, 47 referred for anti-TNF therapy (active-AS; BASDAI ≥4) and 39 with BASDAI<4 (control-AS) were included. The active group was evaluated at baseline, 12-months and 24-months after TNF blockage and compared at baseline to control-AS group and to 47 age- and gender-matched healthy controls. Plasma levels of IL-17A, IL-22, IL-23 and PGE2 were measured. Radiographic severity and progression was assessed by mSASSS.

Results: At baseline, active-AS group presented higher IL-23 and PGE2 levels compared to control-AS group (p<0.001 and p=0.008) and to healthy controls (p<0.001 and p=0.02). After 24-months of TNF blockage, IL-23 and PGE2 remained elevated in which group (I suppose active-AS but you don’t mention control-AS here) with higher levels compared with the healthy group (p<0.001 and p=0.03) in spite of significant improvements in all clinical/inflammatory parameters(p<0.001). Further analysis of 27 anti-TNF-treated patients who achieved a good response(ASDAS-CRP<2.1,with a drop≥1.1) at 24-months revealed that IL-23 plasma levels remained higher than healthy controls(p<0.001) and higher than control-AS group with similar disease activity (ASDAS-CRP<2.1, p=0.01). In active-AS group(n=47), there was a strong positive correlation between IL-23 and IL-17A at baseline, 12-months and 24-months after anti-TNF therapy(p≤0.001).

Conclusion: This study provides novel data demonstrating that IL-23/IL-17 axis is not influenced by TNF blockage in AS patients despite clinical and inflammatory markers. In this context, the IL-23/IL-17 blockage emerges as a potential additional target in AS.

Disclosure: F. M. Milanez, None; C. G. S. Saad, None; V. S. T. Viana, None; J. C. B. Moraes, None; G. V. Périco, None; C. R. Gonçalves, None; E. Bonfá, None, 2.

To cite this abstract in AMA style:

Milanez FM, Saad CGS, Viana VST, Moraes JCB, Périco GV, Gonçalves CR, Bonfá E. Evidence of Serological IL-23/IL-17 Axis Activation in Ankylosing Spondylitis Patients with Long-Term TNF Blockade: The Missing Therapy Target? [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/evidence-of-serological-il-23il-17-axis-activation-in-ankylosing-spondylitis-patients-with-long-term-tnf-blockade-the-missing-therapy-target/. Accessed .

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