Background Tumor necrosis factor (TNF) alpha is responsible for induction of dkk-1 which down-regulates bone formation. Therefore, it was expected that TNF-blocker therapy would inhibit radiographic progression in patients with axSpA but this effect has not been observed yet. Nevertheless, most of the studies have included patients with long disease duration and it is unknown whether or not this effect would be the same in patients with an early stage of the disease.
Objectives To investigate if disease duration influences on the serum levels of dkk-1 in patients with axSpA.
Methods Observational study including consecutive patients with axSpA according to ASAS criteria visiting a tertiary hospital between January 2011 and June 2013. All patients were receiving NSAIDs and none of them was under biologic therapy. The following characteristics were recorded at one visit: Demographic (age, gender), symptoms duration, HLA-B27, disease activity indices (BASDAI, CRP, ESR) and function (BASFI). Blood samples to determine dkk-1 serum levels by enzyme immunoassay were collected at the same visit too. Patients were classified as early axSpA (symptoms duration ≤5 years) and established axSpA (>5 years) and the characteristics enumerated above were compared between both groups. Univariate and multivariate linear regression models were employed to identify the characteristics related to dkk-1 serum levels.
Results Thirty one patients with early axSpA and 21 patients with established disease were included. Patients with early axSpA were younger (32.6±9.3 vs 41.0±10.2 years; p<0.01), had lower degree of disease activity (BASDAI: 4.6±2.7 vs 6.6±1.9; p<0.01 and ESR: 7.7±9.2 vs 18.1±15 mmHg; p<0.05) and worst function (3.2±2.9 vs 5.8±2.5; p<0.01) compared with patients with established disease. Serum levels of dkk-1 were significantly higher in patients with early disease (25.9±11.5 vs 13.9±13.5; p<0.001 ng/dl). No statistically significant differences were found between both groups for the rest of characteristics. In the univariable analysis, symptoms duration and BASDAI were inversely related to dkk-1 levels (std β: -0.435; p<0.01 and Std β: -0.283; p<0.05, respectively). However, only the relationship with symptoms duration remained statistically significant in the multivariable analysis (std β: -0.415; p<0.01).
Conclusions Serum Dkk-1 levels in patients with axSpA depend on disease duration, being higher in patients with recent onset of the disease. The effect of TNF-blocker therapy on radiographic progression may be different in patients with an early stage of the disease compared with patients with established disease.
Acknowledgements VNC and EMM were sponsored by the Spanish Foundation of Rheumatology. This project was supported by the Institute Carlos III and an unrestricted grant from Pfizer.
Disclosure of Interest None declared
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