title: Blockade of intra-articular TNF in peripheral spondyloarthritis: its relevance to clinical scores, quantitative imaging and synovial fluid and synovial tissue biomarkers.
abstract: OBJECTIVE
  This open-label study is based on a translational approach with the aim of detecting changes in the clinical condition as well as in imaging and synovial biological markers in both synovial fluid (SF) and synovial tissue (ST) in peripheral spondyloarthritis (SpA) patients following intra-articular (IA) blockade of TNF-α by serial etanercept injections.
  
  
  METHODS
  Twenty-seven SpA patients with resistant knee synovitis underwent four biweekly IA injections of etanercept (E) (12.5 mg). The primary outcome of Thompson's Knee Index (THOMP), and secondary outcomes of Knee Joint Articular Index (KJAI), C-reactive protein (CRP), HAQ-Disability Index (HAQ-DI), maximal synovial thickness (MST) according to ultrasonography (US) and contrast-enhanced magnetic resonance (C+MR) imaging, ST-CD45+ mononuclear cells (MNC) and ST-CD31+ vessels, IL-1β, IL-1Ra and IL-6 levels in SF were assessed at baseline and at the end of the study.
  
  
  RESULTS
  At the study end, clinical and imaging outcomes as well as ST and SF biological markers were significantly reduced compared to baseline. There were significant correlations between clinical, imaging and biological markers (CRP with either THOMP, or KJAI, or HAQ-DI or SF-IL-1Ra; US-MST with KJAI, ST-CD45+ with either THOMP, or KJAI, or ST-CD31+, or SF-IL-1β; SF-IL-6 with either THOMP, or KJAI, or SF-IL-1β, or IL-1Ra).
  
  
  CONCLUSIONS
  The proof of concept study revealed early improvement either in local and systemic clinical scores, in synovial thickness measures by C+MR and US, or expression of synovial biological markers. CD45+, CD31+ in ST and IL-6 and IL-1β in SF may be considered potential biomarkers of the peripheral SpA response to IA TNF-α blocking.
authors.affiliation: Department of Medicine, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy. ugo.fiocco@unipd.it
authors.forename: Ugo
authors.initials: U
authors.lastname: Fiocco
authors.forename: Paolo
authors.initials: P
authors.lastname: Sfriso
authors.forename: Francesca
authors.initials: F
authors.lastname: Oliviero
authors.forename: Francesca
authors.initials: F
authors.lastname: Lunardi
authors.forename: Fiorella
authors.initials: F
authors.lastname: Calabrese
authors.forename: Elena
authors.initials: E
authors.lastname: Scagliori
authors.forename: Luisella
authors.initials: L
authors.lastname: Cozzi
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Maggio
authors.forename: Roberto
authors.initials: R
authors.lastname: Nardacchione
authors.forename: Béatrice
authors.initials: B
authors.lastname: Molena
authors.forename: Mara
authors.initials: M
authors.lastname: Felicetti
authors.forename: Katia
authors.initials: K
authors.lastname: Gazzola
authors.forename: Roberto
authors.initials: R
authors.lastname: Stramare
authors.forename: Léopoldo
authors.initials: L
authors.lastname: Rubaltelli
authors.forename: Benedetta
authors.initials: B
authors.lastname: Accordi
authors.forename: Luisa
authors.initials: L
authors.lastname: Costa
authors.forename: Pascale
authors.initials: P
authors.lastname: Roux-Lombard
authors.forename: Leonardo
authors.initials: L
authors.lastname: Punzi
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dayer
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000378:metabolism; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007270:Injections, Intra-Articular; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D012720:Severity of Illness Index; D025241:Spondylarthritis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D013582:Synovial Fluid / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013585:Synovitis / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects*
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; C508600:IL6 protein, human; D007074:Immunoglobulin G; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept