Which spinal lesions are associated with new bone formation in patients with ankylosing spondylitis treated with anti-TNF agents? A long-term observational study using MRI and conventional radiography

Ann Rheum Dis. 2014 Oct;73(10):1819-25. doi: 10.1136/annrheumdis-2013-203425. Epub 2013 Jul 14.

Abstract

Objective: To study the relationship of spinal inflammation and fatty degeneration (FD) as detected by MRI and new bone formation seen on conventional radiographs (CRs) in ankylosing spondylitis (AS).

Methods: CRs at baseline, 2 years and 5 years and spinal MRIs at baseline and 2 years of 73 AS patients treated with infliximab in European AS Infliximab Cohort were available. Relative risks (RR) were calculated with a general linear model after adjustment for within-patient variation.

Results: In a total of 1466 vertebral edges (VEs) without baseline syndesmophytes, 61 syndesmophytes developed at 5 years, the majority of which (57.4%) had no corresponding detectable MRI lesions at baseline. VEs with both inflammation and FD at baseline had the highest risk (RR 3.3, p=0.009) for syndesmophyte formation at 5 years, followed by VEs that developed new FD or did not resolve FD at 2 years (RR=2.3, p=0.034), while inflammation at baseline with no FD at 2 years had the lowest risk for syndesmophyte formation at 5 years (RR=0.8). Of the VEs with inflammation at baseline, >70% resolved completely, 28.8% turned into FD after 2 years, but only 1 syndesmophyte developed within 5 years.

Conclusions: Parallel occurrence of inflammation and FD at baseline and development of FD without prior inflammation after 2 years were significantly associated with syndesmophyte formation after 5 years of anti-tumour necrosis factor (TNF) therapy. However, the sequence 'inflammation-FD-new bone formation' was rarely observed, an argument against the TNF-brake hypothesis. Whether an early suppression of inflammation leads to a decrease of the risk for new bone formation remains to be demonstrated.

Keywords: Ankylosing Spondylitis; Anti-TNF; Magnetic Resonance Imaging.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adipose Tissue / pathology
  • Adult
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation / diagnosis
  • Inflammation / etiology
  • Infliximab
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Ossification, Heterotopic / diagnosis
  • Ossification, Heterotopic / etiology*
  • Ossification, Heterotopic / prevention & control
  • Prognosis
  • Severity of Illness Index
  • Spondylitis, Ankylosing / complications*
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / physiopathology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha
  • Infliximab