MADRID – Elevated serum levels of vascular endothelial growth factor may be predictive of radiographic progression in the spine, according to data from a German study of patients with spondyloarthritis.
The cutoff point appears to be at 600 pg/mL, with the effects particularly strong in patients who also develop syndesmophytes, which are bony growths that develop within ligaments.
"In patients with syndesmophytes, VEGF [vascular endothelial growth factor], as a predictor of radiographic progression, performed better than CRP [C-reactive protein]," reported Dr. Denis Poddubnyy at the annual European Congress of Rheumatology (Ann. Rheum. Dis. 2013;72:125).
"We all know that radiographic progression varies substantially among patients with spondyloarthritis," Dr. Poddubnyy observed. "Until recently there was only one strong predictor of radiographic progression: the presence of syndesmophytes at baseline," he added.
Dr. Denis Poddubnyy
Last year, however, Dr. Poddubnyy of Charité Universitätsmedizin Berlin, Germany, and his associates published the findings of a study involving 210 patients with early axial spondyloarthritis (axSpA) who were recruited from the German Spondyloarthritis Inception Cohort (GESPIC). This study looked at baseline predictors of spinal radiographic progression over 2 years and found that in addition to radiographic damage, elevated CRP levels and cigarette smoking were independently predictive (Arthritis Rheum. 2012;64:1388-98).
The team’s research also suggested that there could be a few serum biomarkers, including VEGF, that could be predictive, so the investigators conducted a larger study in 172 patients with definite (n = 95) or nonradiographic (n = 77) axSpA to look specifically at the possible association.
Radiographs of the spine taken at baseline and at 2 years’ follow-up were reviewed independently by two readers, who used the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) to record the extent of radiographic progression. If there was a worsening of 2 units or more in mSASSS and the formation of new or increased growth of syndesmophytes, radiographic progression had occurred.
In total, 22 patients had radiographic progression, including 18 with new formation or growth of syndesmophytes.
Baseline VEGF was measured in the serum at baseline and was significantly higher in patients who developed radiographic progression at 2 years than in those who did not (562 plus or minus 357 pg/mL vs. 402 plus or minus 309 pg/mL; P = .027).
Serum VEGF levels were also significantly higher in the patients who had developed new syndesmophytes at 2 years when compared with those who had not (579 plus or minus 386 pg/mL vs. 404 plus or minus 307 pg/mL; P = .041).
"Patients with elevated VEGF had an odds ratio of 2.9 for [radiographic] progression and 3.1 for syndesmophyte formation," Dr. Poddubnyy reported. This was a little disappointing, he noted, as CRP and the erythrocyte sedimentation rate had similar predictive power.
However, in patients at high risk of progression, namely those with syndesmophytes already present at baseline, VEGF was significantly better than CRP at predicting both radiographic progression and new syndesmophyte formation or growth.
Patients with elevated VEGF at baseline were 36.6 times more likely to have radiographic progression and 13.6 times more likely to have new syndesmophyte formation or growth at 2 years than were those with levels below 600 pg/mL. In comparison, elevated CRP levels increased the risks by only 2.4 and 2.5 times, respectively.
VEGF is an essential mediator of angiogenesis and endochondral ossification, Dr. Poddubnyy observed. It’s been shown to have "a chemoattractive effect on osteoblasts and mesenchymal progenitor cells," he added, and also stimulate osteoblast differentiation and bone turnover.
While the results are very promising, further research is of course required. The possible predictive value of VEGF in relation to spinal radiographic progression in patients treated with tumor necrosis factor–alpha inhibitors remains to be seen, for example, and future studies should perhaps look at this question.
"With VEGF we are probably able to improve our prediction of spinal progression in patients with axSpA," Dr. Poddubnyy said in an interview. This is addition to assessing "classical factors," such as syndesmophytes, CRP, and smoking status.
Dr. Poddubnyy had no disclosures.