Background DKK-1 and SOST are two inhibitory proteins of the Wnt signaling pathway which lead to decreased bone formation by osteoblasts and osteocytes, respectively. Due to the limited data assessing free DKK-1 and SOST in SpA patients under anti-TNF treatment, a post-hoc examination of the SPARSE study was designed in order to answer these question.
Objectives To assess free DKK-1 and SOST serum levels at Baseline and 24 weeks after etanercept or placebo treatment in patients from the SPARSE study.
Methods In the SPARSE study, patients were randomized to receive either etanercept (N=42) or placebo (n=48) in case of active AxSpA disease (defined by mini BASDAI >40) despite optimal NSAIDs intake. The 90 patients from the SPARSE study were quantified for free DKK-1 and SOST serum levels, at Baseline and at Week 8 (w8) corresponding to the end of the placebo controlled period. DKK-1 and SOST serum levels were assessed by the use of a classic sandwich ELISA test (Biomedica, Vienna) and results were provided in pmol/L. Changes in DKK-1 and SOST serum levels were adjusted for disease activity, CRP levels, NSAIDs intake, X-ray status and treatment groups.
Results LS Mean (±SE) serum DKK-1 at Baseline was not significantly different between treatment groups (ETN: 36.2 ± 1.97; PBO: 37.1 ± 1.84; p=0.72). At Baseline, DKK-1 was not associated with any of the patients' or disease characteristics: ASDAS-CRP (r=0.096; 95% CI [-0.122, 0.305]); CRP (r=0.002; 95% CI [-0.210, 0.214]); X-ray status (LS Mean (SE): negative 37.4 (±2.38) versus positive 36.3 (± 1.77); p=0.71). There were no significant differences between treatment groups in the change from Baseline to w8 in the DKK-1 serum levels (p=0.97). We also considered patients with (N=67) or w/o NSAIDs intake (n=19) within the week preceding w8 serum level assessment and found no significant difference (p=0.99). We further assessed DKK-1 serum levels at Baseline according to their Baseline CRP (<6mg/L; ≥6mg/L), X-ray status (Positive; Negative), or NSAIDs intake (Yes; No) within the week preceding w8, and found no significant differences. These analyses were repeated for SOST serum levels at Baseline and with the exception of patients with Negative X-ray status at Baseline having significantly lower values than those patients with Positive X-ray status (p=0.047), no significant differences were observed in terms of the Baseline disease characteristics; Similarly there were no differences between treatment groups in the change from Baseline to w8 SOST serum levels.
Conclusions This post-hoc examination of patients randomized in the SPARSE study suggest that etanercept does not significantly change DKK-1 or SOST serum levels within the 8 first weeks of treatment. Disease activity, CRP, NSAIDs intake and X-ray status were not significantly associated with DKK-1 serum levels. These results should be considered in the context of previous studies suggesting that DKK-1 was dysfunctional in SpA patients (1). Taken together, these results suggest that DKK-1 should not be considered as a valuable bone remodeling marker in SpA, unlike in rheumatoid arthritis.
Daoussis, D., et al. Arthritis Rheum, 62, 150–8
Disclosure of Interest C. Miceli-Richard: None declared, B. Combe: None declared, F. Berenbaum: None declared, T. Schaeverbeke: None declared, N. Koppiker Employee of: Pfizer, I. Logeart Employee of: Pfizer, A. Dubanchet Employee of: Pfizer, M. Dougados: None declared
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