Journal Article

Suppression of inflammation and effects on new bone formation in ankylosing spondylitis: evidence for a window of opportunity in disease modification

Morency, Nathalie, Conner-Spady, Barbara, Maksymowych, Walter P, Lambert, Robert G

2013

Overview

Objectives Although MRI data supports a link between spinal inflammation and formation of new bone in ankylosing spondylitis, anti-tumour necrosis factor α therapies have not been shown to prevent new bone formation. The authors aimed to demonstrate that while acute lesions resolve completely, more advanced lesions, characterised by evidence of reparation, are associated with new bone formation. Methods MRI scans were performed at baseline, 12 and 52 weeks in 76 ankylosing spondylitis patients recruited to a placebo-controlled trial of adalimumab therapy. New syndesmophytes were assessed on lateral radiographs of the cervical and lumbar spine at baseline and 104 weeks. Anonymised MRI scans were read independently by two readers who recorded the presence/absence of acute (type A) and advanced (type B) vertebral corner inflammatory lesions (CIL) and fat lesions. The authors used generalised linear latent and mixed models analysis to adjust for the extent of syndesmophytes/ankylosis at baseline. Results New syndesmophytes developed significantly more frequently from type B CIL (16.7%) compared with type A CIL (2.9%) (p=0.002) or no CIL (2.5%) (p<0.0001). This was also observed for both baseline and new vertebral corner fat lesions evolving over 52 weeks (11.1% (p<0.001) and 6.8% (p=0.03), respectively). The association with type B CIL (OR (95% CI 3.88, 1.20 to –12.57) and fat (OR 95% CI 4.83, 2.38– to 9.80), p<0.0001) was significant after adjustment for the extent of syndesmophytes/ankylosis at baseline. Conclusions Our data supports the hypothesis that new bone formation is more likely in advanced inflammatory lesions and proceeds through a process of fat metaplasia, supporting a window of opportunity for disease modification.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,BMJ Publishing Group,Elsevier Limited
• Subject: Adalimumab / Adult / Antibodies, Monoclonal, Humanized - therapeutic use / Antirheumatic Agents - therapeutic use / Biological and medical sciences / Calcinosis - drug therapy / Calcinosis - etiology / Calcinosis - pathology / Disease Progression / Diseases of the osteoarticular system / Diseases of the spine / Double-Blind Method / Humans / Hypotheses / Inflammation / Inflammation - drug therapy / Inflammation - etiology / Inflammation - pathology / Inflammatory joint diseases / Magnetic Resonance Imaging / Medical sciences / Middle Aged / Osteogenesis - drug effects / Patients / Spondylitis, Ankylosing - complications / Spondylitis, Ankylosing - drug therapy / Spondylitis, Ankylosing - pathology / Studies / Working groups