Serum Biomarkers Predict Ankylosing Spondylitis Progression

Kate Johnson

June 07, 2012

June 7, 2012 (Berlin, Germany) — New research has shown for the first time that serum biomarkers can predict progression of ankylosing spondylitis (AS) in patients already at high risk for progression, reported Joachim Sieper, MD, PhD, here at the European League Against Rheumatism (EULAR) Congress 2012.

"If we concentrate on high-risk patients who already have risk factors, we are able to identify further biomarkers, biomarkers of bone turnover, that are able to predict patients who are fast progressors," said Dr. Sieper, who is from Charité Universitätsmedizin Berlin in Germany, during a press conference.

Using these biomarkers, it might be possible to identify patients who will benefit from early intervention, specifically continuous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), he said.

"This is one of the first studies assessing these markers; of course, it will have to be validated by other ones, but it is an interesting first study," said Xavier Mariette, MD, PhD, from Hôpital Bicêtre in Paris, France, and EULAR scientific chair, in an interview with Medscape Medical News.

The study involved 64 patients with AS, from the German Spondyloarthritis Inception Cohort (GESPIC), who had baseline radiographic evidence of syndesmophytes, indicating an increased risk for progression.

Using radiographs of the lumbar and cervical spine at 2-year follow-up, patients were classified as progressors (n = 26) or nonprogressors (n = 38). Progressors had new development or growth of existing syndesmophytes at 2 years; nonprogressors did not.

Baseline serum levels of the following biomarkers were examined: C-reactive protein (CRP), matrix metalloproteinase 3 (MMP3), sclerostin, Dickkopf 1 (DKK1), periostin, bone morphogenetic protein (BMP) 2 and 7, osteoprotegerin, vascular endothelial growth factor (VEGF), procollagen type I and II N-propeptide (PINP and PIINP), CTX-II, BALP, sRANKL, COPM, and bone sialoprotein.

Dr. Sieper's group recently showed that elevated levels of CRP, an increased erythrocyte sedimentation rate, and cigarette smoking are associated with radiographic progression in early AS (Arthritis Rheum. 2012;64:1388-1398).

The current study confirmed that baseline levels of CRP are higher in progressors than in nonprogressors (17.1 vs 8.7 mg/L; P = .031).

Baseline levels of other serum biomarkers were also higher in patients who eventually progressed than in those who did not: MMP3 (40.2 vs 19.5 ng/mL; P = .016), BMP2 (7.8 vs 5.5 ng/mL; P = .016), PIINP (216.8 vs 126.4 ng/mL; P = .002), and VEGF (602.0 vs 350.7 pg/mL; = .013).

Another recent analysis by Dr. Sieper's group, found that high-dose, long-duration NSAID use reduced radiographic progression in AS (Ann Rheum Dis. Published online March 29, 2012). Dr. Sieper suggested that such use might be warranted in high-risk patients with elevated serum biomarkers.

"Patients who take NSAIDs every day, compared with only every month, have less progression if CRP is elevated, and patients with normal CRP don't benefit. Using these other biomarkers, we hope to identify more accurately patients who will benefit from this kind of treatment," he concluded.

"There is a need for biomarkers to predict the structural progression of AS, and we don't have them yet," Dr. Mariette told Medscape Medical News. "It's always important to be able to predict what will occur in patients, but to be honest, we do not have the therapeutic tools [to respond]," he said.

"It's not like in rheumatoid arthritis, where we have treatments to prevent progression. In AS, this is not the case; for example, antitumor necrosis factor agents do not demonstrate a structural effect. The only drugs for which there are data suggesting the inhibition of structural progression are NSAIDs. It could be an argument for giving NSAIDs continuously in patients at high risk for progression."

Dr. Sieper and Dr. Mariette have disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2012: Abstract OP0091. Presented June 6, 2012.


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