Background/Purpose: Few studies have investigated changes in plasma sclerostin and Dickkopf1 (DKK-1) in relation to other biomarkers of inflammation, cartilage and bone turnover during treatment with tumor-nckrosis-factor-alpha (TNFα) inhibitors. The aim of this study was to investigate plasma concentrations of sclerostin, DKK-1 and serum markers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis (SpA) before and during treatment with adalimumab.

Methods: In a randomized double-blind placebo-controlled trial, 52 patients with axial SpA (77% male, disease duration median 10,range 1-35 years) were allocated to adalimumab 40 mg (n=27) or placebo (n=25) s.c. e.o.w. for 12 weeks, followed by an open label extension, where all received adalimumab. Patients were included if they had: 1) SpA according to ESSG criteria; 2) sacroiliitis on MRI and/or X-rays; and 3) BASDAI ≥40 mm despite treatment with two NSAIDs. Six patients were excluded before week 12 (adalimumab n=2; placebo n=4). At week 24, 43 (83%) patients were BASDAI responders (i.e. reduction of 50% or 20 mm). P<0.005 was regarded as statistical significant. Plasma  sclerostin,  plasma DKK-1, serum  C-reactive protein (CRP), interleukin-6 (IL-6), YKL-40, plasma vascular endothelial growth factor (VEGF), urinary CTX-II, matrix metalloproteinase 3 (MMP-3), total aggrecan (TA), cartilage oligomeric matrix protein (COMP), CTX-I and total osteocalcin (OC) were measured by ELISAs.

Results: Patients with SpA had higher (compared to healthy subjects) baseline levels of IL-6, YKL-40 and CTX-II (p<0.001) and lower levels of aggrecan (p<0.0001). Levels of VEGF, MMP-3, COMP, CTX-I, OC, sclerostin and DKK-1 were within the normal levels. The treatment groups did not differ in baseline biomarker levels. At baseline, IL-6 correlated with CRP (0.73, p<0.0001) and CTX-II (0.48, p=0.0004); VEGF with YKL-40 (0.46, p=0.001); CTX-II with CTX-I (0.40, p=0.004) and OC (0.45, p=0.0008), and OC with CTX-I (0.55, p<0.0001). From baseline to week 12 significant correlations between the percentage changes in IL-6 and CRP (0.76 and 0.67, p<0.0002) and OC (-0.67 and -0.54, p≤0.005) were found in both treatment groups. In the placebo group only CRP and OC (-0.62, p=0.002) correlated and in the adalimumab group only CRP and MMP-3 (0.65, p=0.0004) and TA and YKL-40 (-0.55, p=0.004). From baseline to week 12, patients treated with adalimumab had larger percentage decreases in CRP (p=0.009), IL-6 (p<0.0001) and YKL-40 (p=0.04) compared to placebo treated patients. After 12 weeks of adalimumab treatment significant percentage decreases were seen in CRP (p=0.003), IL-6 (p=0.001), VEGF (p=0.006), YKL-40 (p=0.02) and MMP-3 (0.01). In the placebo group TA (p=0.01) increased. No significant changes were seen for VEGF, CTX-I, MMP-3, TA (adalimumab), DKK-1, sclerostin, CTX-I and OC after the first 12 weeks of treatment.

Conclusion: In patients with SpA treatment with adalimumab significantly reduced biomarkers of inflammation. No significant early changes were seen in sclerostin, DKK-1 and biomarkers of cartilage and bone turnover.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/changes-in-sclerostin-dickkopf-1-and-serum-markers-of-inflammation-cartilage-and-bone-turnover-in-patients-with-axial-spondyloarthritis-treated-with-adalimumab/