Prediction of spinal radiographic progression in patients with radiographic axial spondyloarthritis under TNF inhibitor therapy with serum biomarkers

Axial spondyloarthritis is a chronic, inflammatory rheumatic disease. The main symptom of the disease is inflammatory back pain, although extra-musculoskeletal manifestations such as inflammatory bowel disease or psoriasis might also be present. While the disease is progressing, structural changes of the skeletal systems detectable by X-rays (such as syndemophytes) may occur. This work was aimed at identification of biomarkers with predictive value regarding radiographic spinal progression in patients with axial spondyloarthritis. A total of 137 patients with radiographic axial spondyloarthritis under treatment with TNFa-blockers from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort were included. At Baseline, after 2, 4 and 6 years X-rays were performed and after 3 month, 2 and 6 years blood samples taken. A radiographic progression was either defined as a difference of the Modified Stoke Ankylosing Spondylitis Score (mSASSS) ≥2 after 2 years, ≥4 after 4 years or ≥4 after 6 years or due to syndesmophyte formation ≥1 after 2 years, ≥2 after 4 years or ≥2 after 6 years. The patient's serum samples were evaluated on biomarker concentrations via Sandwich-ELISAs for the following 10 biomarkers: Matrixmetalloproteinase-3 (MMP-3), Calprotectin, Vascular Endothelial Growth Factor (VEGF), Leptin, Visfatin, Sclerostin, Serum Amyloid A (SAA), High- Molecular-Weight-Adiponektin (HMW-Adiponektin), N-terminal propeptid of type II collagen (PIINP) and Osteoprotegerin (OPG). The association of radiographic spinal progression and the single biomarkers and biomarker combinations were analysed with logistics regression and Receiver Operating Characteristic (ROC) analysis. Calprotectin and Visfatin showed a significant association with radiographic progression after 2 years, Leptin a significant association with radiographic progression after 4 years and MMP-3 and Leptin a significant association with the radiographic progression after 6 years. Changes of the serum level of Visfatin and Leptin over the time of 2 years showed a significant association with radiographic spinal progression as well. The biomarkers Visfatin, Calprotectin, Leptin and MMP-3 are associated with spinal radiographic progression.