Inflammatory biomarkers, disease activity and spinal disease measures in patients with ankylosing spondylitis after treatment with infliximab

Ann Rheum Dis. 2008 Apr;67(4):511-7. doi: 10.1136/ard.2007.071605. Epub 2007 Jul 20.

Abstract

Objective: To evaluate the relationship between biomarker levels and disease activity and the spinal inflammation detected by magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS).

Methods: Patients with AS were randomly assigned in a 3:8 ratio to receive infusions of placebo or 5 mg/kg infliximab at weeks 0, 2, 6, 12 and 18. Sera were collected for biomarker analysis at weeks 0, 2 and 24 and were analysed for levels of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF) and C-reactive protein (CRP). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores and pre- and post-gadolinium T1 and short tau inversion recovery MRIs were collected at baseline and week 24.

Results: Significantly greater reductions in IL-6, VEGF and CRP were observed at weeks 2 and 24 in the infliximab group compared with the placebo group (all p<0.001). Baseline IL-6 levels >7.38 pg/ml and CRP levels >1.5 mg/dl were associated with increased rates of clinical response after 24 weeks. Multiple regression analyses showed that reductions from baseline to week 2 in IL-6, but not CRP or VEGF, were significantly associated with reductions in MRI activity and BASDAI scores from baseline to week 24 in the infliximab group (p<0.001).

Conclusions: Significant reductions in IL-6, VEGF and CRP were observed with infliximab compared with placebo. High levels of baseline IL-6 and CRP were associated with clinical response after infliximab treatment. Early reductions in IL-6 were significantly associated with improvements in disease activity and the spinal inflammation detected by MRI.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Female
  • Humans
  • Infliximab
  • Interleukin-6 / blood
  • Magnetic Resonance Imaging
  • Male
  • Predictive Value of Tests
  • Severity of Illness Index
  • Spondylitis, Ankylosing / blood
  • Spondylitis, Ankylosing / drug therapy*
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Biomarkers
  • Interleukin-6
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • C-Reactive Protein
  • Infliximab