Blockade of intra-articular TNF in peripheral spondyloarthritis: its relevance to clinical scores, quantitative imaging and synovial fluid and synovial tissue biomarkers

Joint Bone Spine. 2013 Mar;80(2):165-70. doi: 10.1016/j.jbspin.2012.06.016. Epub 2012 Aug 3.


Objectives: 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.

Trial registration: NCT00678782.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antirheumatic Agents / administration & dosage
  • Biomarkers / metabolism
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / administration & dosage*
  • Injections, Intra-Articular
  • Interleukin 1 Receptor Antagonist Protein / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Receptors, Tumor Necrosis Factor / administration & dosage*
  • Severity of Illness Index
  • Spondylarthritis / diagnosis
  • Spondylarthritis / drug therapy*
  • Spondylarthritis / immunology
  • Synovial Fluid / drug effects*
  • Synovial Fluid / immunology
  • Synovial Fluid / metabolism
  • Synovial Membrane / drug effects*
  • Synovial Membrane / immunology
  • Synovial Membrane / metabolism
  • Synovitis / diagnosis
  • Synovitis / drug therapy
  • Synovitis / immunology
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / adverse effects*


  • Antirheumatic Agents
  • Biomarkers
  • IL6 protein, human
  • Immunoglobulin G
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Interleukin-6
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Etanercept

Associated data