Date: Monday, November 9, 2015
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
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.
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.
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.
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).
To cite this abstract in AMA style:Miceli-Richard C, Combe B, Berenbaum F, Schaeverbeke T, Dilleen M, Koppiker N, Logeart I, Dubanchet A, Dougados M. Free DKK-1 Serum Levels Are Unchanged in Spondyloarthritis Patients Treated By Etanercept [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/free-dkk-1-serum-levels-are-unchanged-in-spondyloarthritis-patients-treated-by-etanercept/. Accessed November 18, 2019.
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