Background/Purpose:

In the recent years several predictors of radiographic spinal progression/syndesmophyte formation in ankylosing spondylitis (AS) were identified: syndesmophytes at baseline (the strongest predictor so far), smoking, elevated level of the C-reactive protein [1]. Furthermore, a number of predictive biomarkers (such as matrix metalloproteinase 3, procollagen II N-terminal propeptide, Wnt-antagonists) were identified, all, however, with a rather modest predictive value. Vascular endothelial growth factor (VEGF) is an essential mediator of the enchondral ossification and, therefore, might play a role in the process of syndesmophyte formation in AS.

The aim of the study was to investigate the predictive role of serum VEGF regarding radiographic spinal progression (new syndesmophytes formation) in patients with AS.

Methods:

Altogether 54 patients with AS from the German Spondyloarthritis Inception Cohort (GESPIC) were included in this analysis. Radiographs of the lumbar (lateral and anteroposterior views) and cervical spine (lateral view) performed at baseline and after 2 years of follow-up were centrally collected, digitized, and subsequently scored independently by two trained readers. Syndesmophytes were considered to be present if both readers agreed on it. Serum VEGF levels were detected at baseline.

Results:

At baseline, syndesmophytes were present in 25 patients (46%), after 2 years of follow-up new syndesmophytes developed in 6 patients (11%).  Mean baseline VEGF value was significantly higher in patients who developed new syndesmophytes in comparison to those without radiographic progression: 544±167 vs 296±159 pg/ml, p=0.004. Receiver operating characteristic (ROC) analysis demonstrated a good performance of VEGF as a predictor of radiographic progression: area under the curve (AUC) = 0.851, p=0.005 – figure. A threshold of 494 (rounded for further analysis to 500) pg/ml demonstrated both high sensitivity (83%) and specificity (92%). Elevated VEGF had a positive predictive value of 56%, negative predictive value of 98%, positive likelihood ratio (LR) = 10, negative LR = 0.18, and an odds ratio (OR) = 55.0 (95% CI 5.1-593.4), p=0.001, as a predictor of new syndesmophytes development. This association remained statistically significant also after adjustment for the baseline level of CRP, presence of syndesmophytes at baseline (or mSASSS at baseline), and smoking status.

Conclusion:

High serum level of VEGF (>500 pg/ml) seems to be highly predictive for development of new syndesmophytes in patients with AS.

References: 1. Poddubnyy D, et al. Arthritis Rheum 2012;64:1388-98. 2. Patil AS, et al. J Cell Physiol 2012;227:1298-308.