IL-23/Th17 Axis is Not Influenced by TNF-blocking Agents in Ankylosing Spondylitis Patients

• Grant number: 16/02494-9
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: May 01, 2016
• End date: October 31, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Eloisa Silva Dutra de Oliveira Bonfá
• Grantee: Eloisa Silva Dutra de Oliveira Bonfá
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Background: Advances in pathophysiology and treatment of ankylosing spondylitis (AS) was recently demonstrated. However, the effect of anti-TNF in the newly described inflammatory pathways involved pathogenesis of this disease remains to be determined. The aim of our study was, therefore, to investigate long-term influence of anti-TNF drugs in IL-23/IL-17 axis of AS patients and their possible correlation with treatment, clinical, laboratory and radiographic parameters. Methods:Eighty-six AS anti-TNF naïve patients, 47 referred for anti-TNF therapy (active-AS; BASDAIe4) and 39 with BASDAI<4 (control-AS) were included. The active group was evaluated at baseline, 12-months and 24-months after TNF blockade and compared at baseline to control-AS group and to 47 healthy age- and gender-matched controls. Plasma levels of IL-17A, IL-22, IL-23 and PGE2 were measured. Non-steroidal anti-inflammatory drugs (NSAIDs) intake were recorded every 6 months. Radiographic severity and progression was assessed by mSASSS at baseline and 24 months after therapy. 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 blockade, IL-23 and PGE2 remained elevated 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 drope1.1) 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 correlation between IL-23 and IL-17A at baseline, 12-months and 24-months after anti-TNF therapy (pd0.001).Conclusion: This study provides novel data demonstrating that the IL-23/IL-17 axis is not influenced by TNF blockade in AS patients despite clinical and inflammation improvements and NSAID intake. (AU)