title: IL-23/Th17 axis is not influenced by TNF-blocking agents in ankylosing spondylitis patients.
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; 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 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 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 correlation between IL-23 and IL-17A at baseline, 12-months and 24-months after anti-TNF therapy (p ≤ 0.001).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Rheumatology, Faculdade de Medicina da Universidade de São Paulo - Reumatologia, Av. Dr. Arnaldo, n° 455, 3° andar, sala 3192, São Paulo, SP, 05403-010, Brazil. femanente@terra.com.br.
authors.forename: Fernanda Manente
authors.initials: FM
authors.lastname: Milanez
authors.affiliation: Division of Rheumatology, Faculdade de Medicina da Universidade de São Paulo - Reumatologia, Av. Dr. Arnaldo, n° 455, 3° andar, sala 3192, São Paulo, SP, 05403-010, Brazil. goncalves-carla@uol.com.br.
authors.forename: Carla G S
authors.initials: CG
authors.lastname: Saad
authors.affiliation: Division of Rheumatology, Faculdade de Medicina da Universidade de São Paulo - Reumatologia, Av. Dr. Arnaldo, n° 455, 3° andar, sala 3192, São Paulo, SP, 05403-010, Brazil. visatv@gmail.com.
authors.forename: Vilma T
authors.initials: VT
authors.lastname: Viana
authors.affiliation: Division of Rheumatology, Faculdade de Medicina da Universidade de São Paulo - Reumatologia, Av. Dr. Arnaldo, n° 455, 3° andar, sala 3192, São Paulo, SP, 05403-010, Brazil. juliocbmoraes@yahoo.com.br.
authors.forename: Júlio C B
authors.initials: JC
authors.lastname: Moraes
authors.affiliation: URC - Unidade Radiológica Criciúma, Rua Antonio de Lucca, 139 - Centro - Criciúma, Santa Catarina, SC, 88811-503, Brazil. gregoryperico@hotmail.com.
authors.forename: Grégory Vinícius
authors.initials: GV
authors.lastname: Périco
authors.affiliation: Division of Rheumatology, Faculdade de Medicina da Universidade de São Paulo - Reumatologia, Av. Dr. Arnaldo, n° 455, 3° andar, sala 3192, São Paulo, SP, 05403-010, Brazil. pdsampaiobarros@uol.com.br.
authors.forename: Percival Degrava
authors.initials: PD
authors.lastname: Sampaio-Barros
authors.affiliation: Division of Rheumatology, Faculdade de Medicina da Universidade de São Paulo - Reumatologia, Av. Dr. Arnaldo, n° 455, 3° andar, sala 3192, São Paulo, SP, 05403-010, Brazil. goncalves.reuma@uol.com.br.
authors.forename: Célio R
authors.initials: CR
authors.lastname: Goncalves
authors.affiliation: Division of Rheumatology, Faculdade de Medicina da Universidade de São Paulo - Reumatologia, Av. Dr. Arnaldo, n° 455, 3° andar, sala 3192, São Paulo, SP, 05403-010, Brazil. eloisa.bonfa@hc.fm.usp.br.
authors.forename: Eloísa
authors.initials: E
authors.lastname: Bonfá
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D015232:Dinoprostone / Q000097:blood* / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D020381:Interleukin-17; D053759:Interleukin-23 / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013167:Spondylitis, Ankylosing / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; C508717:IL17A protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone