Radiographic progression is associated with resolution of systemic inflammation in patients with axial spondylarthritis treated with tumor necrosis factor α inhibitors: a study of radiographic progression, inflammation on magnetic resonance imaging, and circulating biomarkers of inflammation, angiogenesis, and cartilage and bone turnover

Arthritis Rheum. 2011 Dec;63(12):3789-800. doi: 10.1002/art.30627.


Objective: To investigate the relationship of circulating biomarkers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and YKL-40), angiogenesis (vascular endothelial growth factor), cartilage turnover (C-terminal crosslinking telopeptide of type II collagen [CTX-II], total aggrecan, matrix metalloproteinase 3 [MMP-3], and cartilage oligomeric matrix protein [COMP]), and bone turnover (CTX-I and osteocalcin) to inflammation on magnetic resonance imaging (MRI) and radiographic progression in patients with axial spondylarthritis (SpA) beginning tumor necrosis factor α (TNFα) inhibitor therapy.

Methods: MRIs were evaluated according to the Berlin sacroiliac (SI) joint and spine inflammation scoring method at baseline, week 22, and week 46. Radiographs were evaluated using the modified Stoke Ankylosing Spondylitis Spine Score at baseline and week 46. Patients with new syndesmophytes were identified. Biomarker levels in patients were compared to levels in healthy subjects.

Results: Higher pretreatment MRI inflammation scores for SI joints and/or lumbar spine were associated with higher baseline CTX-II levels, but not with higher levels of biomarkers of inflammation and bone turnover. During treatment with TNFα inhibitors, a decrease in MRI inflammation scores from baseline to week 22 was associated with larger percentage decreases in and a normalization of CRP and IL-6 levels as compared to an increase or no change in MRI scores. Development of new syndesmophytes was associated with larger percentage decreases in CRP and IL-6 levels and an increase in osteocalcin level, and with normalization of CRP and IL-6 levels from baseline to week 22. Persistent systemic inflammation was associated with radiographic nonprogression.

Conclusion: Our findings indicate that inflammation on baseline MRI is associated with higher CTX-II levels. Radiographic progression is associated with decreased systemic inflammation, as assessed by IL-6 and CRP levels and MRI, supporting the notion of a link between the resolution of inflammation and new bone formation in SpA patients during anti-TNFα therapy.

Trial registration: NCT00133315.

MeSH terms

  • Adalimumab
  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Biomarkers / blood
  • Bone and Bones / metabolism*
  • C-Reactive Protein / metabolism
  • Cartilage / metabolism*
  • Cartilage Oligomeric Matrix Protein
  • Case-Control Studies
  • Cohort Studies
  • Disease Progression*
  • Extracellular Matrix Proteins / blood
  • Female
  • Glycoproteins / blood
  • Humans
  • Inflammation / diagnostic imaging*
  • Inflammation / pathology*
  • Infliximab
  • Interleukin-6 / blood
  • Magnetic Resonance Imaging
  • Male
  • Matrilin Proteins
  • Matrix Metalloproteinase 3 / blood
  • Middle Aged
  • Neovascularization, Pathologic / blood*
  • Osteocalcin / blood
  • Prospective Studies
  • Radiography
  • Spondylarthritis / blood
  • Spondylarthritis / drug therapy*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / blood


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Cartilage Oligomeric Matrix Protein
  • Extracellular Matrix Proteins
  • Glycoproteins
  • Interleukin-6
  • Matrilin Proteins
  • TSP5 protein, human
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Osteocalcin
  • C-Reactive Protein
  • Infliximab
  • Matrix Metalloproteinase 3
  • Adalimumab

Associated data