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

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 antitumour 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.

Fat Metaplasia and Backfill Are Key Intermediaries in the Development of Sacroiliac Joint Ankylosis in Patients With Ankylosing Spondylitis

“…The demonstration that fat metaplasia at vertebral corners is also associated with the development of new bone supports the hypothesis that fat metaplasia, both in subchondral bone marrow and at sites of erosions, is a key intermediary in the pathophysiology of new bone formation in SpA (5,18).…”

Serum Vascular Endothelial Growth Factor Levels Lack Predictive Value in Patients with Active Ankylosing Spondylitis Treated with Golimumab

“…Our analysis extends these findings by showing that VEGF levels do not predict radiographic progression in patients treated with anti-TNF, although we could confirm that VEGF reduction and MRI-detected spinal inflammation correlate. These findings are consistent with the well-documented ability of TNF antagonists to potently reduce serum inflammatory markers and spinal inflammation acutely, but not to halt radiographic progression in the first years of treatment 4,5,6 , and also with findings from sequential images obtained through MRI and radiograph in the European Ankylosing Spondylitis Infliximab Cohort (EASIC) study 22 .…”

“…Per the EASIC imaging data, the combination of an inflammatory lesion with a fat MRI signal most commonly yielded new bone formation 22 . Although this particular pathology requires further study, it does not appear to involve increases in VEGF serum levels.…”

Challenges and Advances in Targeting Remission in Axial Spondyloarthritis

“…Magnetic resonance imaging (MRI) is important in the assessment of early axSpA, because inflammation and postinflammatory lesions are associated with new bone formation 29 . Discrepancies between "clinical" and "imaging" remission have been observed previously, with only a minority of patients achieving both concurrently 22 .…”