Background/Purpose:

DKK-1 and SOST are two inhibitory proteins of the Wnt signaling pathway that lead to decreased bone formation by osteoblasts and osteocytes, respectively. Functional DKK-1 serum levels have been reported to be decreased and dysfunctional in spondyloarthritis (1,2) and a preliminary study involving a limited number of SpA patients suggested that functional DKK-1 serum levels might also decrease under anti-TNF treatment (2). Due to the limited number of patients included in this latest study and the lack of data assessing free DKK-1 and SOST in SpA, a post-hoc examination of the SPARSE study was designed 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 ≥ 4) despite optimal NSAIDs intake. Free DKK-1 and SOST serum levels were measured in 90 patients from the SPARSE study at Baseline and at Week 8 (w8). 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 patient 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=0.91). 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 for SOST serum levels.

Conclusion:

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 (2).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/free-dkk-1-serum-levels-are-unchanged-in-spondyloarthritis-patients-treated-by-etanercept/