SAT0245 In VIVO Evidence of IL-17/IL-23 Axis Activation in Ankylosing Spondylitis Patients with Long-Term TNF Blockade: The Missing Therapy Target?

Abstract

BackgroundIn spite of recent evidences regarding the relevance of IL-23/IL-17 axis in Ankylosing Spondylitis (AS) pathogenesis, there are no data on the long-term effect of anti-TNF therapy in this pathway and their possible correlation with treatment, clinical, laboratory and radiographic parameters.ObjectivesInvestigate the influence of TNF-blockage in IL-23/IL-17 axis of AS patients.MethodsEighty-six AS patients, 47 with refractory active disease (BASDAI≥4) referred to anti-TNF therapy and 39 AS patients with BASDAI<4 (AS control group) were included. The AS active group was evaluated at baseline, 12 months and 24 months after TNF blockage and compared at baseline to the AS control group and to 47 healthy age- and gender-matched controls. Plasma levels of IL-17A, IL-22, TNFα, IL-23, PGE2 were measured. Radiographic severity and progression was assessed by mSASSS.ResultsAt baseline, active AS patients presented higher IL-23 and PGE2 plasma levels compared to AS control 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 with higher levels compared to healthy group (p<0.001 and p=0.03) in spite of significant improvement in all clinical (ASDAS-CRP, BASFI, BASMI and ASQol, p<0.001) and inflammatory parameters (C-reactive protein and ESR, p<0.001). Further analysis of 27 anti-TNF treated patients that achieved good-response (ASDAS-CRP<2.1 with Δ≥1.1) at 24 months revealed that their IL-23 plasma levels were higher than healthy controls (p<0.001) and higher than 21 AS control group with similar disease activity (ASDAS-CRP<2.1),(p=0.01). No predictor for anti-TNF response or to radiographic progression was identified. In AS active group (n=47), there was a strong correlation between IL-23 and IL-17A at baseline (r=0.64, p<0.001), 12 months (r=0.47, p=0.001) and 24 months (r=0.61, p<0.001). IL-23 was also correlated with PGE2 at 12 months (r=0.45, p=0.001) and 24 months (r=0.33, p<0.05). No correlation was observed between NSAID, cytokines levels and radiographic progression (p>0.05).ConclusionsThis study provides novel data demonstrating that IL-23/IL-17 axis is not influenced by TNF blockage in AS patients despite clinical and inflammation improvement and NSAID intake. In this context, IL-23/IL-17 blockage emerges as potential additional target in AS patients.ReferencesHreggvidsdottir HS, Noordenbos T, Baeten DL. Inflammatory pathways in spondyloarthritis. Mol Immunol 2014;57:28-37.Yeremenko N, Paramarta JE, Baeten D. The interleukin-23/interleukin-17 immune axis as a promising new target in the treatment of spondyloarthritis. Curr Opin Rheumatol 2014;26:361-370.Disclosure of InterestNone declared