Background Non Steroidal Anti-Inflammatory Drugs (NSAIDs) and anti-TNF biologics have been used in patients with ankylosing spondylitis (AS) to suppress inflammation and associated symptoms. Although symptom-modifying, the effects of these interventions on radiographic disease progression are still debated; thus there is an urgent need for biomarkers that can monitor structural disease progression, segregate patients into structural responders and non-responders and assess overall treatment efficacy. Biomarkers of tissue turnover, e.g. collagen degradation fragments – the main structural protein in extracellular matrices - could reflect disease processes of interest.
Objectives We investigated if serum levels of different collagen degradation fragments could be utilized as efficacy biomarkers. Furthermore, we investigated if any of these biomarkers at baseline could predict response to treatment.
Methods Thirty Etanercept (anti-TNF) treated patients were investigated for inflammation and tissue turnover in the first year of treatment. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and matrix metalloproteinase (MMP) degraded CRP (CRPM) evaluated inflammation. MMP-degraded type I, II and III collagen (C1M (connective tissue), C2M (cartilage) and C3M (synovium), respectively) investigated joint destruction. Disease activity was monitored by Bath Ankylosing Spondylitis disease activity index (BASDAI). The biomarker profiles over time were investigated and treatment response was analysed by segregating patients by BASDAI50, CRP and C1M.
Results ESR, CRP, BASDAI and C1M were significantly decreased upon initiation of anti-TNF treatment (p≤0.04). BASDAI50 was not able to segregate patients into those with high and low tissue turnover (C1M, C2M and C3M) after treatment. CRP and C1M could segregate the patients into two structurally different subpopulations, investigated by C2M, C3M and CRPM, one subpopulation which benefitted on C3M and CRPM from treatment (Fig. 1).
Conclusions We found that C1M was a biomarker of treatment efficacy and a biomarker that could select the patients who structurally benefitted from treatment. CRP had the same capacities and ESR and BASDAI were treatment efficacy biomarkers. However, BASDAI50 could not select the patients who structurally benefitted on C3M and CRPM from treatment. C1M was not superior to CRP to select patients who benefitted from treatment, but the biomarkers evaluate different pathologic events, indicating that C1M and CRP identifies two very different events in AS. This illustrates that quantification of C1M and CRP identifies patients who structurally benefit on C3M from Etanercept treatment.
Disclosure of Interest A. S. Siebuhr Employee of: Nordic Bioscience, A.-C. Bay-Jensen Employee of: Nordic Bioscience, M. Karsdal Shareholder of: Nordic Bioscience, Employee of: Nordic Bioscience, R. Lories: None declared, K. de Vlam: None declared